Professor Psaltis has 178 peer-reviewed publications
Toxicol Lett. 2021 Oct 7:S0378-4274(21)00847-X. doi: 10.1016/j.toxlet.2021.09.016. Online ahead of print.
Trimellitic anhydride (TMA) is a chemical agent classified as a low molecular weight (LMW) agent causing occupational rhinitis (OR) or asthma. Although TMA is recognized as a respiratory sensitizer, the direct and non-immunologic effects of TMA remain unclear. Air- liquid interface (ALI) cultured human nasal epithelial cells (HNECs) derived from control subjects were treated with TMA, followed by measurement of the transepithelial electrical resistance (TEER), paracellular permeability of fluorescein isothiocyanate (FITC)-dextran and immunofluorescence of tight junction proteins claudin-1 and zonula occludens-1 (ZO-1). The cytotoxicity of TMA was evaluated by lactate dehydrogenase (LDH) assay. TMA at concentrations of 2 and 4 mg/ml significantly reduced the TEER within 10 minutes (p = 0.0177 on 2 mg/ml; p < 0.0001 on 4 mg/ml). The paracellular permeability of FITC-dextran was significantly increased upon challenge with 4 mg/ml TMA for 3 hours (p = 0.0088) and 6 hours (p = 0.0004). TMA treatment induced a reduction in the fluorescence intensity of claudin-1 and ZO-1 in a dose-dependent manner. LDH assay revealed 4 mg/ml TMA induced cytotoxicity only after 6 hours incubation, while 1 or 2 mg/ml TMA caused no cytotoxicity. Our results suggest that TMA has a potential to penetrate the epithelial barrier by disrupting claudin-1 and ZO-1, indicating an important role for sensitization and OR development.
Microorganisms. 2021 Sep 21;9(9):2001. doi: 10.3390/microorganisms9092001.
A Pseudomonas aeruginosa (P. aeruginosa) airway infection is one of the predominant causes contributing to the high morbidity and mortality rates in cystic fibrosis (CF) patients. The emergence of antibiotic resistant P. aeruginosa strains has led to an urgent need for new therapeutic approaches. Bacteriophages (phages) are viruses that can infect and lyse specific bacteria, providing a potential alternative approach in targeting antibiotic-resistant strains. We aim to isolate and characterise novel P. aeruginosa phages for combination in a cocktail to kill P. aeruginosa. One particular phage, PA4, could lyse 14/20 clinical isolates as observed through spot assays. This phage could significantly reduce the growth of bacteria in vitro, as determined through planktonic adsorption and inhibition assays as well as crystal violet- and LIVE/DEAD-stained biofilm assays. A morphological and genomic analysis revealed that PA4 belongs to the Myoviridae family and contained 66,450 bp. The broad infectivity profile, good stability in various pH and temperature conditions, lytic ability and the absence of the absences of antibiotic resistance, toxic and lysogenic genes suggest that PA4 is a good candidate for clinical grade use. Overall, phage therapy represents a promising alternative treatment option to antibiotics when treating a P. aeruginosa infection.
Curr Opin Otolaryngol Head Neck Surg. 2021 Sep 20. doi: 10.1097/MOO.0000000000000761. Online ahead of print.
PURPOSE OF REVIEW: Allergic fungal rhinosinusitis (AFRS) is a debilitating condition for children. Despite there being several reviews on this topic in the adult population, there is a paucity of reviews of AFRS in the pediatric literature. This article reviews the recent evidence of pediatric AFRS with the aim to optimize outcomes of pediatric patients with this condition.
RECENT FINDINGS: AFRS is clinically characterized by nasal polyposis, a type I hypersensitivity to fungal epitopes, very thick eosinophilic mucin, and peripheral eosinophilia. Pediatric AFRS has similar clinical characteristics to that in adults but is thought to have a more aggressive nature, with higher serum immunoglobulin E and more frequently bone erosion and malformation of facial bones. Diagnosis of pediatric AFRS is made by using the Bent and Kuhn's criteria developed for adult AFRS. The mainstay of treatment is surgery followed by postoperative corticosteroids. Adjunctive therapies, including topical/oral antifungal agents, allergen immunotherapy and biologics may improve outcomes in pediatric AFRS, but to date the current evidence is limited.
SUMMARY: To optimize the outcome of pediatric AFRS, adequate and early diagnosis and treatment are essential. Appropriate and comprehensive endoscopic sinus surgery to open the sinuses, remove the fungal burden of disease and improve access of the sinuses to postoperative topical corticosteroid remains the standard of care.
Pathogens. 2021 Jul 5;10(7):848. doi: 10.3390/pathogens10070848.
Background: Viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) via the spike protein enables endocytosis into host cells using the ACE2 receptor and TMPRSS2. The frequent upper respiratory tract symptoms of COVID-19 and the localization of the virus to the nasopharynx, the most common site of swabbing, indicate that the sinonasal mucosa may play an important role in SARS-CoV2 infection and viral replication. Methods: This paper investigates the presence of ACE2 receptor and TMPRESS2 expression in the primary human nasal epithelial cells (HNECs) from the following: chronic rhinosinusitis without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP) and control (non-CRS) patients, and maps the expression changes when exposed to Th1, Th2, Th17-associated cytokines. Results: We found that ACE2 and TMPRSS2 expression was higher in control HNECs than CRSwNP HNECs, and that both ACE2 and TMPRSS2 were downregulated further by Th2 cytokines in CRSwNP HNECs. Conclusions: This indicates an immune dysregulated state of CRSwNP mucosa, which normally contributes to a chronic inflammatory state, and might support an altered susceptibility to SARS-CoV2 infection and transmission.
Int J Pharm. 2021 Sep 5;606:120927. doi: 10.1016/j.ijpharm.2021.120927. Epub 2021 Jul 23.
Acoustic drug delivery (ADD) is an innovative method for drug delivery to the nose and paranasal sinuses and can be used to treat chronic rhinosinusitis (CRS). The underlying mechanism of ADD is based on the oscillatory exchange of air between the nasal cavity (NC) and the maxillary sinus (MS) through the ostium, which assists with the transfer of the drug particles from the NC to the sinuses. This study aims to examine the efficacy of ADD for drug delivery to the MS using an acoustic wave applied to nebulised aerosols entering the nostril. Here, the effect of acoustic frequency, amplitude, and nebulisation flowrate on the efficiency of ADD to the MS is investigated experimentally. A computational fluid dynamics model was also developed to understand the deposition and transport patterns of the aerosols. The results showed that superimposing an acoustic frequency of 328 Hz, which is the resonance frequency of the selected 3D printed model of the NC-MS combination, on the nebulised aerosols could improve the efficiency of the drug delivery to the MS by 75-fold compared with non-acoustic drug delivery case (p < 0.0001). The experimental data also shows that an increase in the amplitude of excitation, increases the concentration of aerosol deposition in the MS significantly; however, it reaches to a plateau at a sound pressure level of 120 dB re 20 µPa.
Allergy. 2021 May 25. doi: 10.1111/all.14959. Online ahead of print.
BACKGROUND: Chronic rhinosinusitis (CRS) is a common chronic respiratory condition, frequently associated with asthma and affecting the majority of cystic fibrosis (CF) patients. Pseudomonas aeruginosa infections and biofilms have been implicated in recalcitrant CRS. One of the mechanisms of action for bacteria in CRS and CF is mucosal barrier disruption by secreted products that contribute to the inflammation. However, the role of biofilm and planktonic forms of P. aeruginosa in this process is not known. The aim is to determine the effect of P. aeruginosa exoproteins isolated from CF and non-CF CRS patients on the mucosal barrier.
METHODS: Exoproteins from 40 P. aeruginosa isolates were collected in planktonic and biofilm forms and applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs). Mucosal barrier integrity was evaluated by transepithelial electrical resistance (TEER), passage of FITC-dextrans and immunofluorescence of tight junction proteins. Cytotoxicity assays were performed to measure cell viability, and IL-6 ELISA was carried out to evaluate pro-inflammatory effects.
RESULTS: Planktonic exoproteins from 20/40 (50%) clinical isolates had a significant detrimental effect on the barrier and significantly increased IL-6 production. Barrier disruption was characterized by a reduced TEER, increased permeability of FITC-dextrans and discontinuous immunolocalization of tight junction proteins and was significantly more prevalent in isolates harvested from patients with comorbid asthma (P < .05).
CONCLUSION: Exoproteins from planktonic P. aeruginosa clinical isolates from asthmatic CRS patients have detrimental effects on the mucosal barrier and induce IL-6 production potentially contributing to the mucosal inflammation in CRS patients.
Allergy. 2021 Apr 30. doi: 10.1111/all.14883. Online ahead of print.
Staphylococcus aureus is a pathogen of major concern in both acute infections as well as chronic conditions such as chronic rhinosinusitis (CRS). Bacteriophage (phage) therapy has been considered in Western countries as early as the 1920s and has recently regained interest for its potential to treat infections caused by antibiotic resistant strains including Methicillin Resistant Staphylococcus aureus (MRSA). However, bacteria can adapt and become resistant to phages. The ability to overcome phage resistance is considered critically important for phage therapy applications. Here we show that sub-inhibitory concentrations of Protein Synthesis Inhibitor (PSI) antibiotics clindamycin, erythromycin and azithromycin could sensitise phage-resistantS. aureus strains to phages in vitro and in vivo. All 3 antibiotics showed synergy when combined with multiple lytic phages against 9 S. aureus clinicalisolates in planktonic growth and 2 strains forming biofilms. The combination of clindamycin and phages was safe and could eradicate S. aureussinonasal biofilms in a murine model of sinusitis. This data supports the potential use of phage-PSI antibiotic combination therapies in particular for difficult to treat infections with phage-resistantS. aureus and MRSA strains.
Allergy. 2021 Apr 30. doi: 10.1111/all.14883. Online ahead of print.
BACKGROUND: Staphylococcus aureus is a pathogen of major concern in both acute infections and chronic conditions such as chronic rhinosinusitis (CRS). Bacteriophage (phage) therapy has recently regained interest for its potential to treat infections caused by antibiotic resistant strains including Methicillin Resistant Staphylococcus aureus (MRSA). However, bacteria can adapt and become resistant to phages. The aim of this study is to determine the potential for antibiotics to overcome phage resistance.
METHODS: The susceptibility of S. aureus clinical isolates (CIs) to phages J-Sa36, Sa83 and Sa87 alone or in combination with protein synthesis inhibitor (PSI) antibiotics clindamycin, azithromycin and erythromycin was assessed using plaque spot assays, minimum inhibitory concentration (MIC) assays, double layer spot assays and resazurin assays. The safety and efficacy of subinhibitory PSI antibiotics in combination with phage was tested in a Sprague Dawley rat model of sinusitis infected with a phage resistant S. aureus CI.
RESULTS: All three antibiotics at subinhibitory concentrations showed synergy when combined with all 3 phages against S. aureus CIs in planktonic and biofilm form and could sensitize phage-resistant S. aureus to promote phage infection. The combination of topical subinhibitory clindamycin or azithromycin and phage was safe and could eradicate S. aureus sinonasal biofilms in vivo.
CONCLUSION: Subinhibitory concentrations of PSI antibiotics could sensitize phage-resistant S. aureus and MRSA strains to phages in vitro and in vivo. This data supports the potential use of phage-PSI antibiotic combination therapies, in particular for difficult-to-treat infections with phage-resistant S. aureus and MRSA strains.
Colloids Surf B Biointerfaces. 2021 Jun;202:111675. doi: 10.1016/j.colsurfb.2021.111675. Epub 2021 Mar 4.
The emergence of antibiotic resistant bacteria requires for the development of new antimicrobial compounds one of which colloidal silver (CS) having strong bactericidal properties and being the most promising inorganic nanoparticles for the treatment of bacterial infectious diseases. However, their production can be slow and cumbersome. Here, we used Corymbia maculata aqueous leaf extract as a reducing agent to synthesize CS in a single 15-minute process. CS was physico-chemically characterized for shape, size, zeta potential and stability. The Minimal Inhibitory Concentration (MIC) and Minimum Biofilm Eradication Concentration (MBEC) of CS against planktonic and biofilm forms of methicillin-resistant Staphylococcus aureus (MRSA, n = 5), Pseudomonas aeruginosa (n = 5), Haemophilus influenzae (n = 5) and Streptococcus pneumoniae (n = 3) chronic rhinosinusitis clinical isolates were investigated using the microdilution method and resazurin assay, respectively. The in vitro cytotoxicity on bronchial epithelial cells (Nuli-1) was analyzed by the crystal violet proliferation assay. The safety and efficacy of CS was evaluated in an in vivo infection model in Caenorhabditis elegans. CS was spherical in shape with a diameter of between 11-16 nm (TEM analysis) in dried form and 40 nm (NanoSight) in colloidal form and was stable at room temperature and 4 °C for one year. Average MIC and MBEC values varied between 11 and 44 ppm for MRSA, H. influenzae and S. pneumoniae and between 0.2 and 3 ppm for P. aeruginosa. CS was not toxic to Nuli-1 cells or C. elegans at concentrations of 44 ppm and reduced the Colony Forming Units counts by 96.9 % and 99.6 % in C. elegans for MRSA and P. aeruginosa, respectively. In conclusion, a novel, green synthesis of stable CS is demonstrated with good safety and efficacy profiles, particularly against P. aeruginosa in planktonic and biofilm forms. These CS have potential applications against clinical infections, including in the context of CRS.
Pathogens. 2021 Feb 14;10(2):207. doi: 10.3390/pathogens10020207.
Corynebacterium accolens is the predominant species of the healthy human nasal microbiota, and its relative abundance is decreased in the context of chronic rhinosinusitis (CRS). This study aimed to evaluate the antimicrobial potential of C. accolens isolated from a healthy human nasal cavity against planktonic and biofilm growth of Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) clinical isolates (CIs) from CRS patients. Nasal swabs from twenty non-CRS control subjects were screened for the presence of C. accolens using microbiological and molecular techniques. C. accolens CIs and their culture supernatants were tested for their antimicrobial activity against eight S. aureus and eight MRSA 4CIs and S. aureus ATCC25923. The anti-biofilm potential of C. accolens cell-free culture supernatants (CFCSs) on S. aureus biofilms was also assessed. Of the 20 nasal swabs, 10 C. accolens CIs were identified and confirmed with rpoB gene sequencing. All isolates showed variable antimicrobial activity against eight out of 8 S. aureus and seven out of eight MRSA CIs. Culture supernatants from all C. accolens CIs exhibited a significant dose-dependent antibacterial activity (p < 0.05) against five out of five representative S. aureus and MRSA CIs. This inhibition was abolished after proteinase K treatment. C. accolens supernatants induced a significant reduction in metabolic activity and biofilm biomass of S. aureus and MRSA CIs compared to untreated growth control (p < 0.05). C. accolens exhibited antimicrobial activity against S. aureus and MRSA CIs in both planktonic and biofilm forms and holds promise for the development of innovative probiotic therapies to promote sinus health.
Auris Nasus Larynx. 2021 Oct;48(5):890-897. doi: 10.1016/j.anl.2021.01.019. Epub 2021 Jan 30.
OBJECTIVE: Recently, depleted tissue zinc levels were found in nasal mucosa from patients with chronic rhinosinusitis (CRS) in correlation with tissue eosinophilia, however, no clinical biomarkers for tissue zinc levels have been identified. Metallothionein-3 (MT3) is an intracellular zinc chelator and previous data showed MT3 mRNA levels to be reduced in CRS patients with nasal polyps (CRSwNP). In this study, we examined the correlation between MT3 expression and zinc levels in nasal mucosa and primary human nasal epithelial cells (HNECs) to investigate whether MT3 could be a clinical biomarker for tissue zinc levels.
METHOD: Tissue was harvested from 36 patients and mounted on tissue micro-array (TMA) slides. MT3 expression and tissue zinc fluorescence intensity were measured at different areas within the mucosa (surface epithelium and lamina propria) and compared between controls, CRSwNP and CRS without nasal polyps (CRSsNP) patients. MT3 mRNA and protein expression were examined in zinc-depleted HNECs by qPCR and immunofluorescence microscopy.
RESULTS: MT3 expression in CRSwNP was significantly decreased in both surface epithelium (p<0.001 to controls) and lamina propria (p = 0.0491 to controls). There was a significant positive correlation between tissue zinc levels and MT3 expression in nasal mucosa (r = 0.45, p = 0.007). In zinc-deplete HNECs, MT3 expression was significantly decreased at mRNA (p = 0.02) and protein level (p<0.01). There was a significant positive correlation between tissue zinc levels and MT3 expression within individual HNECs (r = 0.59, p<0.001).
CONCLUSIONS: MT3 expression reflects intramucosal zinc levels in both nasal mucosa and HNECs indicating MT3 could be used as a clinical biomarker for monitoring intracellular zinc levels in the nasal mucosa.
Am J Rhinol Allergy. 2021 Sep;35(5):700-712. doi: 10.1177/1945892421989142. Epub 2021 Jan 24.
BACKGROUND: Endoscopic sinus surgery is performed for medically recalcitrant chronic rhinosinusitis. There is no universally accepted strategy regarding post-operative antibiotics despite the high rates of usage worldwide. The aim of this study was to analyse patient-reported and objective outcomes behind antibiotic use following endoscopic sinus surgery.
METHODS: A search of electronic databases was performed. Eligible randomised controlled trials (RCTs) and observational trials were included. The primary outcome was patient reported outcome measures. Secondary outcomes were local infections, endoscopy scores and adverse events. Meta-analysis was performed.
RESULTS: Of 1045 publications identified, 7 were included in the qualitative synthesis and 5 RCTs were included in meta-analysis. Antibiotic regimens varied between studies in terms of antibiotic selection, timing commenced and duration of use. Meta-analysis suggested no significant difference between placebo and antibiotics in patient reported outcome measures (standardised mean difference (SMD) -0.215, 95% confidence interval (CI) -0.637 to 0.207) or endoscopic scores (SMD -2.86, 95% CI -0.846 to 0.273). There was no consistent definition in reporting of infection; therefore, this outcome cannot be comprehensively considered. No severe adverse events were attributable to antibiotics.
CONCLUSIONS: From the studies analysed, there is no level 1 evidence to suggest that antibiotics improved patient outcomes following sinus surgery. However, there was significant heterogeneity in outcome measures and no clear data exists regarding the effects of antibiotics on postoperative infections. The available evidence at present is not enough to make a recommendation in either direction. Further designed larger RCTs are required to investigate these questions in more detail.
PLoS One. 2021 Jan 14;16(1):e0244503. doi: 10.1371/journal.pone.0244503. eCollection 2021.
INTRODUCTION: Adhesions are often considered to be an inevitable consequence of abdominal and pelvic surgery, jeopardizing the medium and long-term success of these procedures. Numerous strategies have been tested to reduce adhesion formation, however, to date, no surgical or medical therapeutic approaches have been successful in its prevention. This study demonstrates the safety and efficacy of Chitogel with Deferiprone and/or antibacterial Gallium Protoporphyrin in different concentrations in preventing adhesion formation after abdominal surgery.
MATERIALS AND METHODS: 112 adult (8-10 week old) male Wistar albino rats were subjected to midline laparotomy and caecal abrasion, with 48 rats having an additional enterotomy and suturing. Kaolin (0.005g/ml) was applied to further accelerate adhesion formation. The abrasion model rats were randomized to receive saline, Chitogel, or Chitogel plus Deferiprone (5, 10 or 20 mM), together with Gallium Protoporphyrin (250μg/mL). The abrasion with enterotomy rats were randomised to receive saline, Chitogel or Chitogel with Deferiprone (1 or 5 mM). At day 21, rats were euthanised, and adhesions graded macroscopically and microscopically; the tensile strength of the repaired caecum was determined by an investigator blinded to the treatment groups.
RESULTS: Chitogel with Deferiprone 5 mM significantly reduced adhesion formation (p<0.01) when pathologically assessed in a rat abrasion model. Chitogel with Deferiprone 5 mM and 1 mM also significantly reduced adhesions (p<0.05) after abrasion with enterotomy. Def-Chitogel 1mM treatment did not weaken the enterotomy site with treated sites having significantly better tensile strength compared to control saline treated enterotomy rats.
CONCLUSIONS: Chitogel with Deferiprone 1 mM constitutes an effective preventative anti-adhesion barrier after abdominal surgery in a rat model. Moreover, this therapeutic combination of agents is safe and does not weaken the healing of the sutured enterotomy site.
Indian J Otolaryngol Head Neck Surg. 2021 Jan 2;73(3):1-3. doi: 10.1007/s12070-020-02298-7. Online ahead of print.
Isolated frontal sinus disease is a rare and highly morbid condition. Although chronic frontal sinusitis has been described in literature, clinically it is quite uncommon in the absence of paranasal sinusitis and rhinitis. Here we examine a case of isolated chronic frontal sinusitis presenting with anosmia-a curious clinical manifestation.
Int Forum Allergy Rhinol. 2020 Nov 24. doi: 10.1002/alr.22741. Online ahead of print.
BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document.
METHODS: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary.
RESULTS: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided.
CONCLUSION: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS. This article is protected by copyright. All rights reserved.
Int Forum Allergy Rhinol. 2021 Mar;11(3):213-739. doi: 10.1002/alr.22741.
EXECUTIVE SUMMARY: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document.
METHODS: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary.
RESULTS: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided.
CONCLUSION: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.
Eur Arch Otorhinolaryngol. 2021 Jun;278(6):1885-1889. doi: 10.1007/s00405-020-06472-z. Epub 2020 Nov 13.
PURPOSE: The distance between the anterior wall of the maxillary sinus and the nasolacrimal duct has been classified into three types by Simmen, in which type I (< 3 mm) is the least feasible for a prelacrimal approach. The aim of our study is to present a surgical technique which overcomes the anatomical limitation of the narrow lacrimal recess (type I) in the management of inverted papilloma in the maxillary sinus.
METHODS: Case series.
RESULTS: Eight patients with type I lacrimal recess underwent surgical resection for inverted papilloma in the maxillary sinus via a prelacrimal approach. The technique is described in detail in the article and essentially involves exposure of the nasolacrimal duct using a diamond burr. Complete tumor excision was achieved in all cases through this access, with no significant intra-operative complications.
CONCLUSIONS: This prelacrimal approach technique is safe and effective for the management of inverted papilloma in maxillary sinuses with a type I lacrimal recess configuration.
Laryngoscope. 2021 Aug;131(8):1697-1703. doi: 10.1002/lary.29261. Epub 2020 Nov 12.
OBJECTIVES/HYPOTHESIS: Lymphoid neogenesis or the development of organised, de novo lymphoid structures has been described increasingly in chronically inflamed tissues. The presence of tertiary lymphoid organs (TLOs) has already been demonstrated to result in significant consequences for disease pathology, severity, prognosis and patient outcomes. Whilst the wider medical community has embraced TLOs as important markers of disease and potential therapeutic targets, the otolaryngology field has only begun turning to these entities in an academic capacity. This review aims to outline the role of tertiary lymphoid organs in disease and summarise key early findings in the ENT field. We also an overview of TLOs, their developmental process and clinicopathological implications.
STUDY DESIGN: Literature review.
METHODS: A literature search for all relevant peer-reviewed publications pertaining to TLOs and ENT diseases. Search was conducted using PubMed, Embase and CINAHL databases.
RESULTS: A total of 24 studies were identified relevant to the topic. The majority of TLO research in ENT fell into the areas of oral squamous cell carcinoma (SCC) and chronic rhinosinusitis (CRS).
CONCLUSIONS: Early research into both oral SCC and CRS suggests that TLOs have significant roles within ear, nose and throat (ENT) diseases. At this point in time, however, TLOs remain somewhat a mystery amongst otolaryngologists. As information in this field increases, we may develop a better understanding of how lymphoid neogenesis can influence disease outcomes amongst our patients and, ultimately, how they can be utilised in an immunotherapeutic manner. Laryngoscope, 131:1697-1703, 2021.
Ear Nose Throat J. 2021 Jun;100(5):295-301. doi: 10.1177/0145561320967727. Epub 2020 Oct 21.
OBJECTIVE: The purpose of this scholarly review is to present an update of the efficacy, safety, and distribution of intranasal corticosteroids (INCS) in the context of treatment for chronic rhinosinusitis (CRS).
MATERIALS AND METHODS: A literature review from 1999 to 2020 of MEDLINE, PubMed, and EMBASE databases was performed, using a comprehensive search strategy. Studies reporting on efficacy, safety, and distribution of all INCS formulations, both Food and Drug Administration (FDA) and non-FDA approved, were reviewed.
RESULTS AND CONCLUSIONS: High-level evidence publications and position papers support the role of INCS in medical treatment for CRS. Significant improvement in disease-specific and general quality of life measures is observed with all formulations of INCS. Overall, the use of both FDA and published non-FDA INCS appears to be safe. Several novel distribution devices might improve penetration to specific areas within the sinuses.
Pathogens. 2020 Oct 10;9(10):828. doi: 10.3390/pathogens9100828.
Chronic Rhinosinusitis (CRS) is a multifactorial disease where microorganisms' innate and adaptive immunity can play a role. This study assessed the total IgG, IgG subclasses, IgE and IgA levels in serum samples from CRS and non-CRS control patients in relation to the disease severity, phenotype, histopathology and comorbidities. Total serum IgG, IgG1, IgG2, IgG3, IgG4 and IgE was determined from 10 non-CRS controls, 10 CRS without nasal polyp (CRSsNP) and 26 CRS with nasal polyp (CRSwNP) patients using ImmunoCap assays. Tissue lysates were analyzed for IgG levels by ELISA. Immunohistochemical analysis was used to measure the expression of IgE and IgG4 in tissue sections. The presence of anti-nuclear antigens (ANAs) against 12 autoantigens in sera and tissue lysates was determined by immunoblot assays. Total serum IgG/IgG1/IgG2 levels were higher in CRS patients vs. controls (p < 0.001), but were not different between CRSwNP and CRSsNP patients (p = 0.57). Serum IgG4/IgE levels were increased in CRSwNP patients compared to controls (p = 0.006), however, this relationship was attenuated by the inclusion of covariates. Serum IgG4 levels were more strongly associated with asthma (p = 0.038, exact median test) and tissue eosinophilia (Spearman's rank rho = 0.51, p = 0.016) than IgE levels. No systemic ANAs were detected in any of the subjects tested. There was a polyclonal increase in serum immunoglobulins in CRS patients with elevated IgG4/IgE levels in CRSwNP patients having tissue eosinophilia and asthma.
J Allergy Clin Immunol. 2021 Jan;147(1):168-178. doi: 10.1016/j.jaci.2020.06.037. Epub 2020 Aug 1.
BACKGROUND: Chronic rhinosinusitis (CRS) has a complex and multifactorial pathogenesis with a heterogeneous inflammatory profile. Proteomic analysis of nasal mucus may enable further understanding of protein abundances and biologic processes present in CRS and its endotypes compared with in healthy patients.
OBJECTIVE: Our aim was to determine differences in the nasal mucus proteome of healthy patients and patients with CRS.
METHODS: Nasal mucus was obtained from healthy patients, patients with CRS without nasal polyps (CRSsNP), and patients with CRS with nasal polyps (CRSwNP) before surgery. Gel electrophoresis was performed to fractionate the complex protein extracts before mass spectrometry analysis. Gene set enrichment analysis was performed on differentially expressed proteins.
RESULTS: A total of 33 patients were included in this study (12 healthy, 10 with CRSsNP, and 11 with CRSwNP). In all, 1142 proteins were identified in mucus samples from healthy patients, 761 in mucus samples from patients with CRSsNP, and 998 in mucus samples from patients with CRSwNP. Dysfunction in immunologic pathways, reduced cellular signaling, and increased cellular metabolism with associated tissue remodeling pathways were present in patients with CRS compared with in healthy patients.
CONCLUSION: Significant downregulation of mucosal immunity and antioxidant pathways with increased tissue modeling processes may account for the clinical manifestations of CRS. Ultimately, the differing proteome and biologic processes provide further insight into CRS pathogenesis and its endotypes.
Rhinology. 2020 Jul 21. doi: 10.4193/Rhin20.055. Online ahead of print.
BACKGROUND: Oral and topical corticosteroids, and antibiotics form the mainstay medical treatment of chronic rhinosinusitis (CRS). Clinical outcomes vary depending on the chosen therapy, resident microbiome and disease phenotype. We conducted a double- blinded, placebo-controlled Randomised Controlled Trial (RCT) to investigate effects of medical therapy on clinical outcomes and associated microbiome shifts.
METHODOLOGY: Fifty eligible patients (CRS with and without polyps) were treated for 3 weeks after randomisation into 3 arms: na- mely oral prednisolone, topical budesonide irrigations and oral doxycycline; each with appropriate placebo. Clinical scoring and microbiome swabs were performed on enrolment, at treatment completion and 3-weeks post treatment completion. Microbiome analysis was performed using the llumina-MiSeq next generation sequencing platform and QIME-2 pipeline.
RESULTS: Significant improvement in clinical scores was observed in prednisolone and budesonide arms at treatment completion but not with antibiotic. Sub-group analysis showed more pronounced effects in patients with polyposis. Corynebacterium and Staphylococcus species predominated, with variable bacterial relative abundance among different treatments at all time-points. The only significant microbiome finding was an increase in bacterial diversity in topical budesonide group immediately after treatment, which returned to baseline 3-weeks post treatment.
CONCLUSION: Clinical improvement was significant with oral and topical steroid but not empirical antibiotic. Although there were some associated microbiome changes with the various treatments, we could not ascertain the consistency of these and whether they do have a clinical significance at all.
Rhinology. 2020 Dec 1;58(6):559-567. doi: 10.4193/Rhin20.055.
BACKGROUND: Oral and topical corticosteroids, and antibiotics form the mainstay medical treatment of chronic rhinosinusitis (CRS). Clinical outcomes vary depending on the chosen therapy, resident microbiome and disease phenotype. We conducted a double- blinded, placebo-controlled Randomised Controlled Trial (RCT) to investigate effects of medical therapy on clinical outcomes and associated microbiome shifts.
METHODOLOGY: Fifty eligible patients (CRS with and without polyps) were treated for 3 weeks after randomisation into 3 arms: na- mely oral prednisolone, topical budesonide irrigations and oral doxycycline; each with appropriate placebo. Clinical scoring and microbiome swabs were performed on enrolment, at treatment completion and 3-weeks post treatment completion. Microbiome analysis was performed using the llumina-MiSeq next generation sequencing platform and QIME-2 pipeline.
RESULTS: Significant improvement in clinical scores was observed in prednisolone and budesonide arms at treatment completion but not with antibiotic. Sub-group analysis showed more pronounced effects in patients with polyposis. Corynebacterium and Staphylococcus species predominated, with variable bacterial relative abundance among different treatments at all time-points. The only significant microbiome finding was an increase in bacterial diversity in topical budesonide group immediately after treatment, which returned to baseline 3-weeks post treatment.
CONCLUSION: Clinical improvement was significant with oral and topical steroid but not empirical antibiotic. Although there were some associated microbiome changes with the various treatments, we could not ascertain the consistency of these and whether they do have a clinical significance at all.
Rhinology. 2020 Oct 1;58(5):451-459. doi: 10.4193/Rhin19.383.
BACKGROUND: Zinc plays an important role in many biological processes. Reduced zinc levels have been found in chronic rhinosinusitis (CRS) patients, however, its role in the pathophysiology of this disease remains unknown. This study examined zinc levels in the serum, mucus and tissue from CRS patients in relation to collagen content and eosinophil infiltration. The effect of zinc depletion on inflammatory cytokine production and collagen synthesis was assessed in vitro.
METHODOLOGY: Zinc levels were determined in serum, mucus and tissue from controls, CRS with (CRSwNP) and without nasal polyps (CRSsNP) patients. Tissue zinc levels, collagen and inflammatory cell infiltration was examined using zinquin assays, immunofluorescence and histology on Tissue Micro Arrays. Cytokine expression and collagen synthesis was evaluated in zinc depleted primary human nasal epithelial cells (HNECs) and primary fibroblasts.
RESULTS: CRSwNP patients showed reduced tissue zinc levels in correlation with a reduction in collagen content, and increased eosinophil numbers. Zinc depletion of HNECs and fibroblasts induced the production of pro-inflammatory cytokines and MUC5AC and reduced collagen secretion.
CONCLUSIONS: These results suggest mucosal zinc depletion associates with tissue eosinophilia and collagen depletion in CRSwNP and induces pro-inflammatory cytokine expression and reduction of collagen synthesis in vitro.
J Laryngol Otol. 2020 Jun;134(6):473-480. doi: 10.1017/S0022215120000882. Epub 2020 Jun 8.
OBJECTIVES: Treatment of inflammatory and neoplastic disease in the maxillary sinus, pterygopalatine and infratemporal fossae requires appropriate surgical exposure. As modern rhinology evolves, so do the techniques available. This paper reviews extended endoscopic approaches to the maxillary sinus and the evidence supporting each technique.
METHODS: A literature search of the Ovid Medline and PubMed databases was performed using appropriate key words relating to endoscopic approaches to the maxillary sinus.
RESULTS: Mega-antrostomy and medial maxillectomy have a role in the surgical treatment of refractory inflammatory disease and sinonasal neoplasms. The pre-lacrimal fossa approach provides excellent access but can be limited because of anatomical variations. Both the transseptal and endoscopic Denker's approaches were reviewed; these appear to be associated with morbidity, without any significant increase in exposure over the afore-described approaches.
CONCLUSION: A range of extended endoscopic approaches to the maxillary sinus exist, each with its own anatomical limitations and potential complications.
Int Forum Allergy Rhinol. 2020 Jul;10(7):871-883. doi: 10.1002/alr.22566. Epub 2020 Jun 7.
BACKGROUND: Chronic rhinosinusitis patients (CRS) suffer from chronic inflammation of the sinus mucosa associated with chronic relapsing infections. Mucosal biofilms, associated with Staphylococcus aureus, have been implicated as a cause. We compared the effect of exoproteins secreted from clinical isolates of S aureus from CRS patients in planktonic and biofilm form on the nasal epithelial barrier.
METHODS: Clinical S aureus isolates from 39 CRS patients were grown in planktonic and biofilm forms and their exoproteins concentrated. These were applied to primary human nasal epithelial cells grown at the air-liquid interface. Transepithelial electrical resistance, permeability of flourescein isothiocyanate-dextrans, and cytotoxicity were measured. Structure and expression of tight junctions zona occludens-1, and claudin-1 proteins were assessed by electron microscopy and immunofluorescence. The Wilcoxon signed rank test was used for statistical analyses.
RESULTS: S aureus biofilm exoproteins showed dose- and time-dependent reduction of transepithelial electrical resistance, increased cell toxicity, and increased permeability (p < 0.001) compared with equal concentrations of planktonic cultures. Discontinuity in zona occludens-1 and claudin-1 immunofluorescence was confirmed as disrupted tight junctions on electron microscopy.
CONCLUSION: S aureus biofilm exoproteins disrupt the mucosal barrier structure in a time- and dose-dependent manner and are toxic. Damage to the mucosal barrier by S aureus biofilm exoproteins may play a major role in CRS etiopathogenesis.
Rhinology. 2020 Oct 1;58(5):418-429. doi: 10.4193/Rhin20.034.
BACKGROUND: Progressive advances in proteomic technology has improved our understanding of the chronic rhinosinusitis (CRS) pathogenesis and endotypes. This scoping review aims to present a comprehensive and descriptive analysis of nasal mucosa and mucus proteome of CRS patients.
METHODOLOGY: Studies investigating the proteome of nasal mucosa and mucus from healthy and CRS patients via mass spectrometry were included. Critical appraisal of methodological quality was conducted with extraction of protein lists. Gene set enrichment analysis (GSEA) was performed on studies including CRS patients.
RESULTS: 2962 proteins were identified in the 21 studies included in this review. Eleven studies investigated the nasal mucus proteome and ten studies investigated the nasal mucosa proteome. Studies demonstrated heterogeneity in patients, sampling and mass spectrometry methodology. Samples from CRS patients suggested a trend in enrichment of immune system and programmed cell death pathways. Increased expression of proteins involved in cellular components including the cytoskeleton and adherens junctions was also present in CRS.
CONCLUSIONS: Alterations in the healthy sinonasal proteome may lead to the increased immunological, metabolic and tissue remodeling processes observed in CRS. However, it is difficult to draw significant conclusions from the GSEA due to the heterogeneity present in the limited literature available. These findings allow us to direct further research to better understand CRS pathogenesis and its endotypes.
Front Surg. 2020 Apr 8;7:12. doi: 10.3389/fsurg.2020.00012. eCollection 2020.
Background: Adhesion formation after abdominal surgery is considered almost inevitable and a major cause of morbidity. Novel treatments have been proposed, however there is a lack of suitable small animal models for pre-clinical evaluation, mainly due to inconsistency in adhesion formation in positive control animals. Here, we propose a new rat model of abdominal adhesions using Kaolin as the adhesion-inducing agent at an optimized dosage for testing newer agents in respect to their anti-adhesive property. Materials and Methods: Twenty-five adult (8-10 week old) male Wistar albino rats underwent midline laparotomy and caecal abrasion and were randomized to receive topical applications of normal saline or different concentrations and volumes of a Kaolin-based formulation. At day 14 rats were humanely killed, and adhesions graded macroscopically by an investigator blinded to the treatment groups, using pre-determined adhesion scores and microscopically using histopathology. Results: Kaolin at 0.005 g/mL caused consistent adhesions without compromising rat viability. At higher doses significant morbidity and mortality was observed in the animals treated. Conclusions: Kaolin induced adhesion in a rat abdominal surgery model is reliable and can be safely used to test the efficacy of novel anti-adhesive formulations to prevent intra-abdominal adhesions.
Front Cell Infect Microbiol. 2020 Apr 8;10:137. doi: 10.3389/fcimb.2020.00137. eCollection 2020.
This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal "microbiotypes" or "states": the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus, suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future.
Front Cell Infect Microbiol. 2020 Mar 19;10:110. doi: 10.3389/fcimb.2020.00110. eCollection 2020.
Introduction: Antibiotics are often administered to patients perioperatively and have been shown to affect ROS production of nasal cells in vitro, but their effect in the setting of active wound healing remains unclear. Reactive oxygen species (ROS) are known to play a significant role in wound healing. This study analyzed a broad array of antibiotics used after sinus surgery to assess their effect on wound healing and ROS production in vitro. It was hypothesized that ROS production would be affected by these antibiotics and there would be a negative relationship between ROS activity and cell migration speed. Methods: Monolayers of primary human nasal epithelial cells (HNEC) and primary fibroblasts were disrupted with a linear wound, treated with 10 different antibiotics or a ROS inhibitor and observed over 36 h in a controlled environment using confocal microscopy. ROS activity and migration speed of the wound edge were measured at regular intervals. The relationship between the two parameters was analyzed using mixed linear modeling. Results: Performing a linear scratch over the cell monolayers produced an immediate increase in ROS production of ~35% compared to unscratched controls in both cell types. Incubation with mitoquinone and the oxazolidinone antibiotic linezolid inhibited ROS activity in both fibroblasts and HNEC in association with slowed fibroblast cell migration (p < 0.05). Fibroblast cell migration was also reduced in the presence of clarithromycin and mupirocin (p < 0.05). A significant correlation was seen between ROS suppression and cell migration rate in fibroblasts for mitoquinone and all antibiotics except for azithromycin and doxycycline, where no clear relationship was seen. Treatments that slowed fibroblast cell migration compared to untreated controls showed a significant correlation with ROS suppression (p < 0.05). Conclusion: Increased ROS production in freshly wounded HNEC and fibroblast cell monolayers was suppressed in the presence of antibiotics, in correlation with reduced fibroblast cell migration. In contrast, HNEC cell migration was not significantly affected by any of the antibiotics tested. This differential effect of antibiotics on fibroblast and HNEC migration might have clinical relevance by reducing adhesion formation without affecting epithelial healing in the postoperative setting.
Int Forum Allergy Rhinol. 2020 Oct;10(10):1141-1148. doi: 10.1002/alr.22575. Epub 2020 Jun 7.
BACKGROUND: Nasal topical treatments can provide an effective method of disease control for patients suffering from chronic rhinosinusitis (CRS). However, some frequently used formulations lack adequate evaluation on their safety. This study investigated the effect of 0.5% povidone-iodine (Nasodine) on the sinonasal epithelial barrier and ciliated human nasal epithelial cells (HNECs) in vitro.
METHODS: Nasodine was applied to air-liquid interface (ALI) cultures of primary HNECs from CRS patients. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER), paracellular permeability, and immunolocalization of the zona occludens-1 (ZO-1) tight junction protein. Toxicity and ciliary beat frequency (CBF) were also studied.
RESULTS: Nasodine was not toxic and did not have detrimental effects on the paracellular permeability or CBF. Nasodine did not show a significant reduction in TEER with a 5-minute exposure; however, with a 30-minute exposure there was a significant reduction in TEER at 1 hour and at 4 hours after exposure.
CONCLUSION: Application of Nasodine to HNEC-ALI cultures in vitro for up to 30 minutes was not toxic and did not affect the paracellular permeability or CBF.
Am J Rhinol Allergy. 2020 Sep;34(5):604-609. doi: 10.1177/1945892420914185. Epub 2020 Mar 19.
BACKGROUND: Published reports on the vascular anatomy of the inferior turbinate (IT) are limited. Historical papers report the IT artery as a tributary off the posterior lateral nasal artery (PLNA), but this has not been our clinical experience.
OBJECTIVE: The purpose of this study was to examine the arterial blood supply to and the branching pattern within the IT. We discuss this is the context of IT surgery and relate it to postoperative bleeding complication rates.
METHODS: Endoscopic dissection was performed on 16 cadaver heads (24 sides) to determine the origin of the IT artery. Intraoperative surgical videos were analyzed in 50 patients to uncover the vascular branching pattern within the IT. A retrospective review of bleeding complications in patients undergoing IT reduction surgery was also conducted.
RESULTS: In 17 of 24 sides (70.8%), the IT artery arose either exclusively (54.2%) or partly (16.6%) off the descending palatine artery (DPA). As a branch off the DPA, the IT artery exited the pterygopalatine fossa through a foramen located 7.7 ± 3.0 mm from posterior edge of the IT, 8.4 ± 3.1 mm above the nasal floor and 1.6 ± 2.1 mm below the insertion of the IT bone onto the lateral nasal wall. The mean number of arteries cascading within the IT was 2.7 ± 0.5. Moreover, 112 patients underwent IT reduction surgery and 2 (1.8%) experienced postoperative epistaxis.
CONCLUSION: The IT artery has major contributions from the DPA. Most commonly 3 arteries branch within the IT. Knowledge of this vascular anatomy may minimize bleeding associated with IT reduction surgery.
Allergy. 2020 Aug;75(8):2037-2049. doi: 10.1111/all.14276. Epub 2020 Mar 30.
The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota.
Rhinology. 2020 Jun 1;58(3):273-283. doi: 10.4193/Rhin19.403.
BACKGROUND: RNA sequencing (RNA-Seq) allows the characterization of a global transcriptomic signature in a least-biased fashion, but few studies have applied this method to investigate the pathophysiology of CRS.
METHODS: We collected mucosal tissue samples from 6 CRS without nasal polyps (CRSsNP), 6 CRS with nasal polyps (CRSwNP), and 6 control patients. Additional matched polyp samples were collected from the 6 CRSwNP patients. RNA was extracted and sequenced on the Illumina HiSeq-2500. Differential gene expression and pathway analyses were performed.
RESULTS: CRSsNP showed evidence of upregulated interferon-mediated immunity, MHC-class-I mediated antigen presentation, CXCR3 binding, neutrophil chemotaxis and degranulation, and potential downregulation of genes related to cilia movement and production. CRSwNP polyp tissue showed upregulation of B-cell mediated immune responses, but reduced expression of genes related to epithelial morphogenesis and haemostasis. Polyps also showed a generalized reduction of positive gene regulation. The sinonasal transcriptomic signature was largely determined by tissue type (polyp versus mucosa) and disease phenotype, with minimal signal originating from the individual patient.
CONCLUSION: RNA-Seq is a useful tool to explore the complex pathophysiology of CRS. Our findings stress the importance of tissue selection in molecular research utilizing sinonasal tissue, and demonstrate the limitation of the sNP/wNP paradigm (and the importance of endotyping). On the other hand, classical CRSsNP/wNP disease phenotypes played some role in determining the global transcriptomic signature, and should not be hastily discarded. The value of RNA-Seq-described transcriptomic signatures in exploring endotypes is yet to be explored in future studies.
Rhinology. 2020 Feb 20;58(Suppl S29):1-464. doi: 10.4193/Rhin20.600.
The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: https://www.rhinologyjournal.com.
Expert Opin Pharmacother. 2020 Mar;21(4):427-433. doi: 10.1080/14656566.2020.1717467. Epub 2020 Jan 23.
Introduction: Rhinosinusitis is an extremely prevalent condition with significant health-care expenditure and socio-economic burden. Although symptomatically patients with acute and chronic rhinosinusitis present similarly, the underlying pathogenesis of these conditions is different.Areas covered: This perspective discusses the various treatment options for both acute and chronic rhinosinusitis and examines some of the challenges in choosing appropriate pharmacotherapy. It examines the evidence supporting the commonly used agents including saline irrigations, topical and oral corticosteroids and antibiotics and makes recommendations based on the highest level of evidence available. Furthermore, the role or precision medicine and emerging therapies such as biologics are discussed.Expert opinion: Despite being commonly prescribed, the evidence supporting the routine use of oral antibiotics for CRS and the majority of ARS is lacking. The authors suggest judicious use of these medications after clear consideration of the indications. Topical intranasal corticosteroids and saline irrigations remain a safe and effective treatment for rhinosinusitis and should be considered as first-line therapy. In patients who fail to respond to appropriate treatment, therapy should be escalated after consultation and review by a specialist.
Exp Biol Med (Maywood). 2020 Jan;245(1):34-41. doi: 10.1177/1535370219896779. Epub 2020 Jan 5.
Staphylococcus aureus and Pseudomonas aeruginosa are primary pathogens in chronic rhinosinusitis (CRS), and the presence of S. aureus and P. aeruginosa biofilms has been associated with negative outcomes after surgery. This study investigated the inhibition effect of cetylpyridinium chloride (CPC)-quatsomes at low concentrations on both S. aureus and P. aeruginosa biofilms in vitro, as well as their toxicities towards cultured human airway epithelial (NuLi-1) cells. S. aureus ATCC 25923 and P. aeruginosa ATCC 15692 were used to establish biofilms. CPC-quatsome and CPC micelle solutions at concentrations of 0.01%, 0.025%, and 0.05% were prepared. AlamarBlue was used to test the viability of both planktonic S. aureus and P. aeruginosa and their biofilms after treatment for 5 min and 2 h, respectively. Confocal laser scanning microscopy (CLSM) was used to investigate the interactions between CPC-quatsomes and S. aureus and P. aeruginosa biofilms. A lactate dehydrogenase (LDH) assay was used to determine the toxicity of CPC-quatsomes on NuLi-1 cells. CPC-quatsome and CPC micelle solutions had significant inhibition effects at all tested concentrations on planktonic S. aureus and P. aeruginosa and their biofilms after 5-min exposure (P < 0.05). In the CLSM study, different interactions between CPC-quatsomes and S. aureus or P. aeruginosa biofilms were observed. After 2-h treatment, the size of S. aureus biofilms decreased, while the number of dead bacteria increased in P. aeruginosa biofilms. Neither CPC-quatsomes nor CPC micelle solutions showed significant toxicity on NuLi-1 cell at all tested CPC concentrations (P < 0.05). CPC-quatsomes at low concentrations inhibited S. aureus and P. aeruginosa in both planktonic form and biofilms. No adverse effects on NuLi-1 cells were observed, indicating their promising potential in the treatment of CRS.
IMPACT STATEMENT: Staphylococcus aureus and Pseudomonas aeruginosa biofilms are significant contributors to chronic rhinosinusitis (CRS), and are associated with poor prognosis. The killing effect of CPC-quatsomes on S. aureus biofilm at or above the CPC concentration of 0.5% (5 mg/mL) has been reported previously. This is the first study that showed the significant inhibition effect of CPC-quatsomes at low concentrations on both S. aureus and P. aeruginosa biofilms in vitro, and no adverse effects towards cultured human airway epithelial (NuLi-1) cells. In our study, CPC-quatsomes at concentrations of 0.01%, 0.025%, and 0.05% had significant inhibition effects on both planktonic and biofilms of S. aureus and P. aeruginosa. The result of this study indicates the promising potential of CPC-quatsome in the treatment of CRS.
Ophthalmic Plast Reconstr Surg. 2020 Jan/Feb;36(1):80-85. doi: 10.1097/IOP.0000000000001473.
PURPOSE: Acquired nasolacrimal duct obstruction (NLDO) is a common problem leading to epiphora, the pathophysiology of which remains unclear. Culture-based studies have found Staphylococcal species to be the most prevalent organisms, reported in 47% to 73% of patients with NLDO. Recently, culture-independent molecular methods of have allowed more comprehensive detailing of local microbiota. This study aims to evaluate the sinonasal and lacrimal microbiome of patients undergoing dacryocystorhinostomy for NLDO using 16S-amplicon sequencing.
METHODS: Guarded intraoperative swabs were taken from the middle meatus (MM), inferior meatus, and the opened lacrimal sac of 14 NLDO patients undergoing dacryocystorhinostomy and from the inferior meatus and MM on the contralateral unaffected side. MM swabs from 12 control patients were compared with NLDO patients.
RESULTS: Comparing microbiota at lacrimal sac to MM and inferior meatus sites reveals that the lacrimal sac microbiome is dominated by Staphylococci (36.3%) and Corynebacterium (35.8%). No significant genus differential abundance between the 3 sites, and between the ipsilateral and contralateral sinonasal swabs, and no convincing evidence of reduced alpha diversity in all comparisons. There was a statistically significant lower relative abundance of Corynebacterium (37.6% vs. 65.1%; p = 0.035) in the MM of NLDO patients compared with controls.
CONCLUSIONS: The lacrimal sac microbiome in acquired NLDO is similar to the sinonasal microbiome. The relative abundance of Corynebacterium was reduced compared with controls. These findings suggest that an altered sinonasal microbiome may be associated with NLDO, either as a consequence or a risk factor, and merits future research.The authors have demonstrated a decreased relative abundance of Corynebacterium at the middle meatus of patients with ipsilateral nasolacrimal duct obstruction (NLDO), compared with controls, and that the lacrimal sac microbiome is similar to the sinonasal microbiome. An altered microbial state may, therefore, be associated with NLDO, either as a consequence or a risk factor, and merits future research.
Curr Opin Otolaryngol Head Neck Surg. 2020 Feb;28(1):25-30. doi: 10.1097/MOO.0000000000000598.
PURPOSE OF REVIEW: Topical therapies play an important role in the management of chronic rhinosinusitis (CRS). A detailed literature review was undertaken to appraise recent evidence surrounding current topical therapies and novel treatments used in the setting of recalcitrant CRS.
RECENT FINDINGS: Effective sinus surgery aids in the delivery of topical therapies. Budesonide nasal rinses delivered by saline irrigation offer clinical and symptomatic improvements pre and postoperatively with a well-proven safety profile. Topical steroids may additionally offer direct antibacterial effects as per in-vitro testing. Topical antibiotics are not recommended in routine practice; however, they may be of benefit for short-term eradication therapy. Novel treatments are under keen investigation and include bacteriophage, colloidal silver and manuka honey. The evidence base for these treatments is not robust enough to recommend their routine use at present.
SUMMARY: Topical steroids delivered in conjunction with saline nasal irrigation offer the best combination of treatments in CRS and should be considered a standard of care. Wide surgical access and aggressive surgical debridement of polyposis facilitates the delivery of steroid irrigations to sinonasal mucosa and is associated with improved long-term outcomes following endoscopic sinus surgery. The use of novel treatments remains within the research setting alone.
J Clin Med. 2019 Oct 4;8(10):1617. doi: 10.3390/jcm8101617.
BACKGROUND: Chronic rhinosinusitis (CRS) is defined as a chronic inflammation of the nose and paranasal sinus mucosa associated with relapsing infections-particularly with S. aureus. Long-term treatments with protein synthesis inhibitor antibiotics have been proposed to reduce inflammation in the context chronic severe inflammatory airway pathologies, including CRS. This study assessed the effect of subinhibitory clindamycin and azithromycin on S. aureus exoprotein induced inflammation, toxicity and invasiveness.
METHODS: S. aureus ATCC51650 and two clinical isolates grown in planktonic and biofilm form were treated with subinhibitory clindamycin and azithromycin. Exoproteins were collected and applied to primary human nasal epithelial cells (HNECs) in monolayers and at air-liquid interface. This was followed by lactate dehydrogenase (LDH), enzyme-linked immunosorbent assay (ELISA), Transepithelial Electrical Resistance (TEER) and paracellular permeability assays to assess the effect on cell toxicity, inflammatory cytokine production and mucosal barrier structure and function, respectively. The effect of these treatments was tested as well on the S. aureus invasiveness of HNECs.
RESULTS: Subinhibitory clindamycin reduced S. aureus exoprotein production in planktonic and biofilm form, thereby blocking exoprotein-induced toxicity, reversing its detrimental effects on mucosal barrier structure and function and modulating its inflammatory properties. Sub-inhibitory azithromycin had similar effects-albeit to a lesser extent. Furthermore, clindamycin-but not azithromycin-treated S. aureus lost its invasive capacity of HNECs.
CONCLUSION: Subinhibitory clindamycin and azithromycin reduce S. aureus exoprotein production, thereby modulating the inflammatory cascade by reducing exoprotein-induced toxicity, inflammation, mucosal barrier disruption and invasiveness.
Int Forum Allergy Rhinol. 2019 Dec;9(12):1470-1477. doi: 10.1002/alr.22423. Epub 2019 Aug 28.
BACKGROUND: Manuka honey (MH) has significant antibiofilm activity in vitro and in vivo against Staphylococcus aureus, methicillin-resistant S aureus (MRSA), and Pseudomonas aeruginosa. This is the first randomized, single-blinded, placebo-controlled phase 1 clinical trial investigating the safety and preliminary efficacy of MH with augmented methylglyoxal (MGO) rinses in recalcitrant chronic rhinosinusitis (CRS).
METHODS: Patients were included after previously undergoing endoscopic sinus surgery and presenting with signs and symptoms of sinus infection with positive bacterial cultures on sinus swabs. Patients were randomized to receive 14 days of twice-daily 16.5% MH + 1.3 mg/mL MGO sinonasal rinses and concurrent 10 days of placebo tablets (MH), or 14 days of twice-daily saline sinonasal rinses and concurrent 10 days of culture-directed antibiotic therapy (CON). Safety observations included the University of Pennsylvania Smell Identification Test (UPSIT) and adverse-event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund-Kennedy scores (LKSs), and symptom scores using the visual analog scale (VAS) and 22-item Sino-Nasal Outcome Test (SNOT-22).
RESULTS: Twenty-five patients completed the study. MH demonstrated a good safety profile with no major AEs and no changes in UPSIT. Six of 10 (60%) MH patients had a reduction in bacterial culture rate with 1 of 10 of those having negative cultures, compared with 12 of 15 (80%) in the control group with 7 of 15 having negative cultures upon completion of the study.
CONCLUSION: This study concludes that twice-daily 16.5% MH augmented with 1.3 mg/mL MGO sinonasal rinses alone for 14 days is safe but not superior to culture-directed oral antibiotics and twice-daily saline rinses.
Int Forum Allergy Rhinol. 2019 Oct;9(10):1220-1226. doi: 10.1002/alr.22401. Epub 2019 Aug 12.
BACKGROUND: The neutrophil serine proteases neutrophil elastase (NE), cathepsin G (CG), and proteinase 3 (PR3) are implicated in the regulation of inflammatory conditions. Pseudomonas aeruginosa elastase (PE), also a serine protease, has been found to behave similarly to NE and has been proposed to assist the pathogen in evading the host immune response. The effect of serine proteases on human nasal epithelial barrier function requires further investigation to better understand the pathophysiology of inflammatory conditions.
METHODS: Purified human neutrophil serine proteases and PE were applied to primary human nasal epithelial cells grown at air-liquid interface (HNEC-ALI) cultures from 6 patients. Barrier integrity and function was assessed via transepithelial electrical resistance (TER), permeability assays, immunofluorescence of Zona occludens-1 (ZO-1), and ciliary beat frequency (CBF) measurements. Cytotoxicity assays were employed to assess cell viability. Interleukin 6 (IL-6) and IL-8 enzyme-linked immunosorbent assay (ELISA) assessed cytokine release from HNEC-ALI.
RESULTS: The application of serine proteases showed detrimental effects on HNEC-ALI barrier integrity. Reduction in TER occurred with NE, CG, and PE with increased paracellular permeability with NE, CG, PR3, and PE. Discontinuous tight junctions with reduction in ZO-1 expression were identified using immunofluorescence. Neutrophil serine proteases were not toxic cells to the HNECs and had no detrimental effects on the CBF.
CONCLUSION: Serine proteases derived from neutrophils and from P. aeruginosa showed detrimental effects on the mucosal barrier integrity with increased permeability, allowing for potential bacterial invasion. This finding may further assist in understanding the pathophysiology present in chronic inflammatory airway diseases.
Rhinology. 2019 Jul 25;57(Suppl S28):1-41. doi: 10.4193/Rhin19.410.
The accurate diagnosis of rhinologic disease depends on the clinical history, examination findings and, in many cases, further investigations. There are a wide variety of diagnostic tests available, the choice of which depends upon the condition being assessed. This position paper is intended to provide an up-to-date comprehensive description of the diagnostic tools available to rhinologists, allergists, general otolaryngologists and other physicians with an interest in sinonasal disease. The literature has been reviewed and evidence-based recommendations are included. The relevant history and examination techniques are described, including endoscopic assessment of the nose. General and disease-specific quality of life instruments are an important tool in assessing the impact of rhinologic disease and the response to treatment. Relevant blood tests are discussed, as well as the various methods of allergy testing. Techniques for collecting microbiological and tissue samples are described, as well as the use of more specialised tests such as nasal nitric oxide and those evaluating ciliary structure and function. Imaging techniques and their indications are included. Chemosensory (smell and taste) testing is explained, and the available techniques for objective measurement of nasal airflow and patency are reviewed. Prompt and accurate diagnosis allows appropriate management to be initiated; an understanding of the currently available diagnostic tools is a vital part of the assessment of rhinologic disease.
Int Forum Allergy Rhinol. 2019 Oct;9(10):1097-1104. doi: 10.1002/alr.22397. Epub 2019 Jul 25.
BACKGROUND: Middle meatal antrostomy (MMA) provides limited access to the anteromedial and inferior aspect of the maxillary sinus (MS) often resulting in residual disease and inflammatory burden. Newer extended procedures, such as mega-antrostomy (Mega-A) and extended modified mega-antrostomy (EMMA), have been developed to address this limitation. This study assesses the effect of varying extent of MS surgery on irrigation penetration and access of instrumentation.
METHODS: The MS of 5 fresh-frozen cadavers were sequentially dissected. Irrigation was evaluated with a squeeze bottle (SB) in different head positions and using different volumes of fluid. Surgical reach and visualization were examined using common sinus instruments and different angled endoscopes. A disease simulation was also performed to check for residual debris after instrumentation and irrigations.
RESULTS: Irrigation penetration improved as antrostomy size increased (p < 0.0001), with a significant difference observed between the extended procedures and MMA. The effect of the volume was significant for SB (p < 0.0001) but head positions appeared irrelevant (p = 0.613). Overall visualization improved for Mega-A and EMMA. A similar trend was seen for the reach of the instruments to all sinus wall subsites. EMMA facilitated the most removal of "sinus disease" in the disease simulation model when compared with both MMA and Mega-A, due to its reach of the anteroinferior aspects of the maxillary sinus.
CONCLUSIONS: High-volume irrigation using SB achieved good sinus penetration, irrespective of head position. Extended MS procedures appear to further increase irrigation penetration as well as surgical access.
J Craniofac Surg. 2019 Jul;30(5):e454-e460. doi: 10.1097/SCS.0000000000005533.
BACKGROUND: Velopharyngeal insufficiency is a feared complication of adenoidectomies in patients with palatal abnormalities. Thus, the benefits of adenoidectomy in this population are less understood. The techniques of partial adenoidectomy aim to preserve velopharyngeal closure while sufficiently debulking the nasal airway to ameliorate obstruction and snoring.
METHODOLOGY: Systematic review of online databases using a combination of search terms including "cleft palate," "submucosal cleft palate," "short palate," "adenoidectomy," "partial adenoidectomy," "subtotal adenoidectomy," and "powered adenoidectomy." Two independent reviewers assessed the eligibility of each study based on predefined inclusion criteria.
RESULTS: From 323 studies identified, 8 were included. All were retrospective case series, except 1 prospective study. Study period ranged from 1.1 to 14 years (median 7.5 years). There were 172 patients with a cleft palate (n = 80), submucous cleft palate (n = 67) or another defined palatal abnormality [short soft palate (n = 14), bifid uvula (n = 4), questionable palatal mobility (n = 4) or incomplete CP (n = 3)] identified. Mean age was 5.5 years and just over half were male (58%). Nearly all patients showed improvement in nasal airway obstruction and snoring. The pooled risk for velopharyngeal insufficiency across all studies was 2 out of 122, which approximates to 1.6% of patients. There were very few complications.
CONCLUSION: This is the first systematic review of partial adenoidectomy in patients with palatal abnormalities. Sub-total adenoidectomy in patients with submucosal cleft palate or repaired cleft palate appears to be a safe and efficacious procedure. There is; however, a need for prospective data collection using a standardized technique in large patient series required to properly assess outcomes.
JAMA Otolaryngol Head Neck Surg. 2019 Aug 1;145(8):723-729. doi: 10.1001/jamaoto.2019.1191.
IMPORTANCE: Staphylococcus aureus infections are associated with recalcitrant chronic rhinosinusitis (CRS). The emerging threat of multidrug-resistant S aureus infections has revived interest in bacteriophage (phage) therapy.
OBJECTIVE: To investigate the safety, tolerability, and preliminary efficacy of ascending multiple intranasal doses of investigational phage cocktail AB-SA01 in patients with recalcitrant CRS due to S aureus.
DESIGN, SETTING, AND PARTICIPANTS: This phase 1, first-in-humans, open-label clinical trial of multiple ascending doses was conducted at a single tertiary referral center from December 1, 2015, through September 30, 2016, with follow-up completed on December 31, 2016. Patients with recalcitrant CRS (aged 18-70 years) in whom surgical and medical treatment had failed and who had positive S aureus cultures sensitive to AB-SA01 were recruited. Findings were analyzed from February 2 through August 31, 2017.
INTERVENTIONS: Three patient cohorts (3 patients/cohort) received serial doses of twice-daily intranasal irrigations with AB-SA01 at a concentration of 3 × 108 plaque-forming units (PFU) for 7 days (cohort 1), 3 × 108 PFU for 14 days (cohort 2), and 3 × 109 PFU for 14 days (cohort 3).
MAIN OUTCOMES AND MEASURES: The primary study outcome was the safety and tolerability of intranasal AB-SA01. Safety observations included vital signs, physical examinations, clinical laboratory test results, and adverse events. The secondary outcome was preliminary efficacy assessed by comparing pretreatment and posttreatment microbiology results, disease-relevant endoscopic Lund-Kennedy Scores, and symptom scores using a visual analog scale and Sino-Nasal Outcome Test-22.
RESULTS: All 9 participants (4 men and 5 women; median age, 45 years [interquartile range, 41.0-71.5 years]) completed the trial. Intranasal phage treatment was well tolerated, with no serious adverse events or deaths reported in any of the 3 cohorts. No change in vital signs occurred before and 0.5 and 2.0 hours after administration of AB-SA01 and at the exit visit. No changes in biochemistry were found except for 1 participant in cohort 3 who showed a decrease in blood bicarbonate levels on exit visit, with normal results of physical examination and vital signs. All biochemistry values were normalized 8 days later. No changes in temperature were recorded before, during, or after treatment. Six adverse effects were reported in 6 participants; all were classified as mild treatment-emergent adverse effects and resolved by the end of the study. Preliminary efficacy results indicated favorable outcomes across all cohorts, with 2 of 9 patients showing clinical and microbiological evidence of eradication of infection.
CONCLUSIONS AND RELEVANCE: Intranasal irrigation with AB-SA01 of doses to 3 × 109 PFU for 14 days was safe and well tolerated, with promising preliminary efficacy observations. Phage therapy could be an alternative to antibiotics for patients with CRS.
TRIAL REGISTRATION: https://anzctr.org.au identifier: ACTRN12616000002482.
Int Forum Allergy Rhinol. 2019 Aug;9(8):918-925. doi: 10.1002/alr.22360. Epub 2019 Jun 4.
BACKGROUND: Chronic rhinosinusitis (CRS) is a common disease, often refractory to conventional antimicrobial treatment. In this study we investigate the antimicrobial and anti-inflammatory effects of adding kappa-carrageenan to a commercially available sinus rinse.
METHODS: Kappa-carrageenan was added to Flo CRS and Flo Sinus Care sinus rinses and applied directly to air-liquid interface cultured primary human nasal epithelial cells (HNECs) from 10 CRS patients. Inflammatory markers were measured using enzyme-linked immunosorbent assay. Kappa-carrageenan-supplemented sinus rinses were applied to human bronchial epithelial cells (HBEs) in the presence of different Staphylococcus aureus strains to observe the effect on intracellular infection rates.
RESULTS: Flo Sinus Care with kappa-carrageenan rinse solutions resulted in a marked reduction of interleukin-6 (IL-6) production by HNECs from CRS patients (p = 0.007). Both Flo CRS and Flo Sinus Care rinses significantly reduced the S aureus intracellular infection of HBEs (p < 0.0001). The addition of kappa-carrageenan to both Flo CRS and Flo Sinus Care rinses further reduced the intracellular infection rate by an average of 2%.
CONCLUSIONS: The commonly used sinus irrigation product Flo Sinus Care with added kappa-carrageenan reduces IL-6 production by HNECs in vitro. Flo CRS and Flo Sinus Care rinses significantly reduced S aureus intracellular infection rates of HBE cells. Our findings may have clinical relevance for CRS patient management.
Ann Anat. 2019 Jul;224:28-32. doi: 10.1016/j.aanat.2019.03.010. Epub 2019 Apr 3.
PURPOSE: To provide a review of the anatomy of the lacrimal drainage system and lateral wall of the nose pertaining to endoscopic dacryocystorhinostomy.
METHODS: The authors performed a PubMed search of articles published pertaining to the anatomy of the lateral wall of the nose and the anatomy of endonasal and external dacryocystorhinostomy surgery.
RESULTS: The article covers the regional surface and surgical anatomy for endoscopic dacryocystorhinostomy (DCR), including the maxillary line, middle turbinate, agger nasi air cell, lacrimal sac and fossa and the upper portion of the nasolacrimal drainage system. It also explores the dimensions and location of bony ostium formation to ensure full exposure and marsupialisation of the lacrimal sac. Finally, it covers the anatomy of potential complications of endoscopic DCR surgery including penetration of the skull base and orbit, inadvertent entry to the maxillary sinus and breach of the skin.
CONCLUSION: A good understanding of the anatomy of the lacrimal drainage system and the lateral wall of the nose will increase the likelihood of successful surgery and minimize the risk of complications and damage to neighbouring structures such as the orbit and skull base.
Orbit. 2020 Feb;39(1):1-4. doi: 10.1080/01676830.2019.1582072. Epub 2019 Mar 20.
Purpose: To evaluate the outcomes of powered endoscopic dacryocystorhinostomy (DCR) in syndromic individuals with congenital nasolacrimal duct obstruction (CNLDO).Methods: A retrospective multicenter case series of patients who required a primary powered endoscopic DCR for refractory CNLDO associated with syndromes or congenital craniofacial abnormalities was performed. A minimum follow-up of more than 6 months was considered for final analysis. Main outcome measures were anatomical and functional success at the last follow up.Results: Twenty primary powered endoscopic DCR's were performed in 12 patients (7 males, 5 females) with syndromic anomalies. The mean age at the time of surgery was 7.6 years (range: 2-22 years). The associated systemic anomalies were Down syndrome (42%, 5/12), ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome (17%, 2/12), gross craniofacial dysgenesis (25%, 3/12) Tessier cleft type 3 (8%, 1/12) and velocardiacfacial syndrome (8%, 1/12). Proximal system agenesis of the upper or lower canaliculus was present in 42% of patients (5 patients, 9 eyes). Adjunctive treatment in the form of Mitomycin C and/or intubation was performed in 55% (11/20) eyes. At a mean postoperative follow-up of 20 months, successful outcomes were noted in 95% of the eyes (19/20). The one eye with an anatomical failure was secondary to a complete cicatricial closure of the ostium and was successfully treated subsequently with a revision endoscopic DCR.Conclusion: Primary powered endoscopic DCR has good outcomes in patients with a CNLDO associated with craniofacial syndromes.
Front Cell Infect Microbiol. 2019 Feb 27;9:38. doi: 10.3389/fcimb.2019.00038. eCollection 2019.
Background: Pseudomonas aeruginosa causes severe chronic respiratory diseases and is associated with recalcitrant chronic rhinosinusitis (CRS). P. aeruginosa exoproteins contain virulence factors and play important roles in the pathogenicity of P. aeruginosa, however their role in CRS pathophysiology remains unknown. Methods: We isolated P. aeruginosa clinical isolates (CIs) and obtained clinical information from 21 CRS patients. Elastase activity of the CIs was measured at different phases of growth. Primary human nasal epithelial cells (HNECs) were cultured at air-liquid interface (ALI) and challenged with P. aeruginosa exoproteins or purified elastase, followed by measuring Transepithelial Electrical Resistance (TEER), permeability of FITC-dextrans, western blot, and immunofluorescence. Results: 14/21 CIs had a significant increase in elastase activity in stationary phase of growth. There was a highly significant strong correlation between the in vitro elastase activity of P. aeruginosa CIs with mucosal barrier disruption evidenced by increased permeability of FITC-dextrans (r = 0.95, p = 0.0004) and decreased TEER (r = -0.9333, P < 0.01) after 4 h of challenge. Western blot showed a significant degradation of ZO-1, Occludin and β-actin in relation to the elastase activity of the exoproteins. There was a highly significant correlation between the in vitro elastase activity of P. aeruginosa CIs and CRS disease severity (for log phase, r = 0.5631, p = 0.0097; for stationary phase, r = 0.66, p = 0.0013) assessed by CT imaging of the paranasal sinuses. Conclusion: Our results implicate P. aeruginosa exoproteins as playing a major role in the pathophysiology of P. aeruginosa associated CRS by severely compromising mucosal barrier structure and function.
Sci Rep. 2019 Feb 20;9(1):2378. doi: 10.1038/s41598-019-38902-2.
Normal wound healing is a highly regulated and coordinated process. However, tissue injury often results in inflammation with excessive scar tissue formation after 40-70% of operations. Here, we evaluated the effect of the iron chelator deferiprone on inflammation and the migration of primary nasal fibroblasts and primary human nasal epithelial cells (HNECs) in vitro. The cytotoxicity of deferiprone was examined by the lactate dehydrogenase assay on primary nasal fibroblasts and air-liquid interface (ALI) cultures of HNECs. Wound closure was observed in scratch assays by using time-lapse confocal scanning laser microscopy. Interleukin-6 (IL-6) and type I and III collagen protein levels were determined by ELISA. Intracellular Reactive Oxygen Species (ROS) activity was measured by utilizing the fluorescent probe H2DCFDA. Deferiprone at 10 mM concentration was non-toxic to primary fibroblasts and HNECs for up to 48 hours application. Deferiprone had significant dose-dependent inhibitory effects on the migration, secreted collagen production and ROS release by primary nasal fibroblasts. Deferiprone blocked Poly (I:C)-induced IL-6 production by HNECs but did not alter their migration in scratch assays. Deferiprone has the potential to limit scar tissue formation and should be considered in future clinical applications.
Am J Rhinol Allergy. 2019 May;33(3):323-330. doi: 10.1177/1945892419826228. Epub 2019 Feb 13.
BACKGROUND: To date, there are numerous studies documenting the prevalence of frontal recess cells, but only 1 study using the newly developed International Frontal Sinus Anatomical Classification (IFAC) system. The identification of the frontal cells and their influence on the frontal drainage pathway plays an important role in endoscopic frontal sinus surgery.
OBJECTIVE: The aim of this study is to document the radiological prevalence of various types of frontal cells, as classified by IFAC and the most common frontal sinus drainage pathways based on its anatomic relationships with these cells.
METHODS: Using a novel preoperative virtual planning software (Scopis Building Blocks), consecutive computerized tomography scans of the sinuses of patients were analyzed for the prevalence of frontal cells, as classified by the by IFAC, and the frontal sinus drainage pathways at the Ear Nose Throat Hospital of Ho Chi Minh City, Vietnam.
RESULTS: In this study, 208 computed tomography scans of consecutively selected frontal sinuses of 114 patients were included for analysis. The agger nasi cell was present in 95.7% of reviewed scans. The frontal cells prevalence was as follows: supra agger cell (SAC): 16.3%, supra agger frontal cell (SAFC): 13%, supra bulla cell (SBC): 46.2%, supra bulla frontal cell (SBFC): 4.3%, supra orbital ethmoid cell: 17.3%, and frontal septal cell: 10.6%. The most common frontal sinus pathway type in relation to frontal cells was medial to SAC (70.6%), medial to SAFC (81.5%), anterior to SBC (88.5%), and anterior to SBFC (100%). In cases that had 2 frontal cells group, the drainage pathway was medial to SAC/SAFC and anterior to SBC/SBFC in most cases.
CONCLUSION: This study documents the prevalence of frontal cells (classified by IFAC) using a novel preoperative virtual planning software in the Vietnamese population. It demonstrates predominantly medial anteromedial frontal drainage pathways as related to these frontal cells.
Int Forum Allergy Rhinol. 2019 Jul;9(7):766-775. doi: 10.1002/alr.22312. Epub 2019 Feb 12.
BACKGROUND: Topical budesonide (Pulmicort; AstraZeneca AB, Sodertalje, Sweden) is commonly used in the management of chronic rhinosinusitis (CRS). Although its use is due to its perceived anti-inflammatory effect, studies have suggested that it may also have antibacterial properties. To make the hydrophobic steroid molecule suitable for topical administration, pharmaceutical excipients are used in commercial steroid formulations. Herein we investigated the antibacterial action of commercial budesonide and its excipients.
METHODS: Planktonic and biofilm forms of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) were treated with Pulmicort or its excipients at clinically relevant concentrations. Bacterial growth was determined by optical density, resazurin assays, colony-forming unit counts, and Giemsa staining. Minimum inhibitory concentration (MIC) studies assessed excipients' potentiation of antibiotics. Experiments were conducted in triplicate and results analyzed using one-way analysis of variance.
RESULTS: There was significant reduction in planktonic and biofilm growth of S aureus and MRSA on exposure to budesonide (p < 0.0001) and its excipients (p < 0.0001). Excipient ethylene diamine-tetraactic acid (EDTA) demonstrated an antibacterial property even at the low concentrations used in topical preparations (p < 0.0001). With amoxicillin, excipients exhibited a potential additive/synergistic effect on MIC, whereas erythromycin and aminoglycosides showed an antagonistic action.
CONCLUSION: The commercial product Pulmicort has a direct antibacterial effect on the planktonic and biofilm forms of S aureus and MRSA. This effect is at least in part mediated through the excipient EDTA in the product. Excipients also influenced the antimicrobial activity of antibiotics depending on the bacterial strain and antibiotic tested.
Curr Protoc Toxicol. 2019 Jun;80(1):e69. doi: 10.1002/cptx.69. Epub 2019 Feb 4.
Here we use the toll-like receptor (TLR) 3 agonist poly I:C (LMW) to induce an inflammatory response in cells of submerged and/or air-liquid interface (ALI) cultures of human nasal epithelial cells (HNECs). The inflammatory response is determined by measuring interleukin-6 (IL-6) protein levels by enzyme-linked immunosorbent assay (ELISA). The mucosal barrier integrity is determined by measuring transepithelial electrical resistance (TEER) and passage of fluorescently labeled dextrans. Stimulation with poly (I:C) LMW induces a 15- to 17-fold increase in IL-6 production by HNEC-ALI cells. © 2019 by John Wiley & Sons, Inc.
Laryngoscope. 2019 Jun;129(6):1265-1273. doi: 10.1002/lary.27726. Epub 2019 Jan 22.
OBJECTIVE: The role of the microbiome in the etiology of chronic rhinosinusitis (CRS) is still in debate. Reductions in richness and diversity have been implicated in CRS; however, limited knowledge exists regarding the impact of the severity of disease on the microbiome. The associations between constituents of the microbiome and the degree of mucosal inflammation and tissue eosinophilia are described.
METHODS: A cross-sectional study of CRS and non-CRS patients who underwent endoscopic sinus surgery was performed. Sinus mucosal biopsies were assessed for the degree of inflammation and tissue eosinophilia. Middle-meatal swabs were subjected to 16S rRNA gene sequencing, which quantified the prevalence, mean relative abundance, richness, and diversity. Comparisons between the microbiome at the genus level and degree of inflammation (absent, mild, moderate, severe) and tissue eosinophilia (absent, < 10, 10-100, > 100 per high-powered field) were performed.
RESULTS: Eight-nine patients (52.8 ± 14.21 years, 64.0% male) were assessed. Of those, 52 had CRS and 37 were controls. Corynebacterium and Staphylococcus were the most abundant genera in both the CRS (29% and 16%) and non-CRS groups (40% and 20%). Richness decreased in more severely inflamed patients (23.2 ± 13.9 vs. 18.1 ± 16.1 vs. 16.8 ± 12.3 vs. 14.7 ± 10.9; P < 0.01), as did diversity (1.4 ± 0.7 vs. 1.2 ± 1.0 vs. 1.2 ± 0.8 vs. 0.9 ± 0.7; P = 0.05). Richness was associated with higher tissue eosinophilia (23.2 ± 13.9 vs. 19.3 ± 17.2 vs. 15.9 ± 11.6 vs. 13.4 ± 6.6; P < 0.01).
CONCLUSION: The loss of richness and diversity seen in the CRS microbiome appears to be a product of severity of inflammation and tissue eosinophilia. Whether this dysbiosis is causative or a result of the disease with impaired epithelial integrity requires ongoing research.
LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1265-1273, 2019.
Int Forum Allergy Rhinol. 2019 Apr;9(4):378-387. doi: 10.1002/alr.22288. Epub 2019 Jan 15.
BACKGROUND: Chronic rhinosinusitis (CRS) patients who fail medical management have few treatment options other than endoscopic sinus surgery (ESS). A novel biodegradable mometasone furoate drug delivery system (LYR-210) providing continuous topical steroid therapy to sinonasal mucosa over 24 weeks was developed to treat unoperated CRS patients who have failed medical management prior to ESS. LYR-210 was designed to slowly expand in the middle meatus, ensuring efficient drug delivery as mucosal swelling reduces.
METHODS: A prospective, multicenter, open-label study was conducted in 20 CRS subjects who were determined to be candidates for ESS. Under endoscopic guidance and topical anesthesia, LYR-210 was placed in both middle meatuses. The primary endpoint was product-related serious adverse events (SAEs) at 4 weeks. Additional assessments included plasma drug concentration, morning serum cortisol levels, intraocular pressures (IOPs), and Sino-Nasal Outcome Test (SNOT-22) scores.
RESULTS: LYR-210 was successfully placed bilaterally in 20 subjects (12 without nasal polyps and 8 with polyps) in an office setting. There were no product-related SAEs through 24 weeks, at which point 86% of LYR-210 depots were still retained in the middle meatus. Serum cortisol, IOP, and plasma drug concentrations supported systemic safety at all time points tested. Subjects experienced significant reductions in their SNOT-22 scores as early as week 1, and this reduction persisted through week 24 (p < 0.01). Significant symptom improvement was achieved in the SNOT-22 rhinologic, extranasal rhinologic, ear-facial, psychological, and sleep dysfunction subdomains at 24 weeks (p < 0.05).
CONCLUSION: LYR-210 is safe and well-tolerated in ESS-naive CRS patients and leads to sustained symptom improvement in patients.
Transl Res. 2019 Apr;206:41-56. doi: 10.1016/j.trsl.2018.12.002. Epub 2018 Dec 19.
Pseudomonas aeruginosa (PA) is a bacterial pathogen that frequently displays antibiotic resistance. Its presence within the sinuses of chronic rhinosinusitis sufferers is associated with poorer quality of life. Obligately lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death. The aims of this study were to assess the safety and efficacy of a PA phage cocktail (CT-PA) in a sheep model of rhinosinusitis. The sheep rhinosinusitis model was adapted to simulate PA infection in sheep frontal sinuses. To assess efficacy, after a 7-day biofilm formation period, sheep received twice-daily frontal trephine flushes of CT-PA or saline for 1 week. Biofilm quantitation on frontal sinus mucosa was performed using LIVE/DEAD BacLight staining. To assess safety, sheep received twice-daily frontal trephine flushes of CT-PA or vehicle control for 3 weeks. Blood and fecal samples were collected throughout treatment. Histopathology of frontal sinus, lung, heart, liver, spleen, and kidney tissue was performed. Sinus cilia were visualized using scanning electron microscopy (SEM). The Efficacy arm showed a statistically significant reduction in biofilm biomass with all concentrations of CT-PA tested (P < 0.05). Phage presence in sinuses was maintained for at least 16hours after the final flush. All Safety arm sheep completed 3 weeks of treatment. Phage was detected consistently in feces and sporadically in blood and organ samples. Histology and SEM of tissues revealed no treatment-related damage. In conclusion, CT-PA was able to decrease sinus PA biofilm at concentrations of 108-1010 PFU/mL. No safety concerns were noted.
Int Forum Allergy Rhinol. 2019 Feb;9(2):187-196. doi: 10.1002/alr.22232. Epub 2018 Nov 15.
BACKGROUND: Staphylococcus aureus is a major contributor to the pathophysiology of chronic rhinosinusitis (CRS). Previous research has shown that S. aureus-secreted products disrupt the airway barrier.
METHODS: S. aureus ATCC 13565 and 25923 strains were grown at exponential, postexponential, and stationary phases. Microbial conditioned media (CM) was collected from the cultures and ultrafiltered (UF). Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was performed on the UF-CM. UF-CM was subjected to heat and protease treatment, size fractionation, and ultracentrifugation (UC) separation. Human nasal epithelial cells grown at air-liquid interface (HNEC-ALI) cultures were exposed to purified alpha hemolysin (Hla), staphylococcal enterotoxin A (SEA), lipoteichoic acid (LTA), and UF-CM. Barrier function outcomes were measured by transepithelial electrical resistance (TEER) and apparent permeability (Papp). UC fraction exposed cultures were subjected to immunofluorescence microscopy for tight junction (TJ) protein zonula occludens-1 (ZO-1).
RESULTS: LC-ESI-MS/MS identified 107 proteins, with Hla being most abundant. Hla, SEA, and LTA did not alter the HNEC-ALI barrier as measured by TEER or Papp. Barrier disruption caused by UF-CM peaked in the postexponential phase, was sensitive to heat and protease treatment, >30-kDa in size, and enriched in the UC fraction. HNEC-ALI exposed to UF-CM and UC demonstrated loss of ZO-1 localization.
CONCLUSION: These results suggest that the S. aureus factor responsible for TJ disruption in HNEC-ALI cultures is either a protein-macromolecule or a combination of secreted factors. The product is enriched in the UC fraction, suggesting it is associated with large structures such as membrane components or vesicles.
BMC Ear Nose Throat Disord. 2018 Oct 16;18:16. doi: 10.1186/s12901-018-0064-1. eCollection 2018.
BACKGROUND: Staphylococcus aureus has a high prevalence in chronic rhinosinusitis (CRS) patients and is suggested to play a more etiopathogenic role in CRS patients with nasal polyps (CRSwNP), a severe form of the CRS spectrum with poorer surgical outcomes. We performed a microbial genome-wide association study (mGWAS) to investigate whether S. aureus isolates from CRS patients have particular genetic markers associated with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP).
METHODS: Whole genome sequencing was performed on S. aureus isolates collected from 28 CRSsNP and 30 CRSwNP patients. A mGWAS approach was employed using large-scale comparative genomics to identify genetic variation within our dataset.
RESULTS: Considerable genetic variation was observed, with > 90,000 single nucleotide polymorphisms (SNPs) sites identified. There was little correlation with CRS subtype based on SNPs and Insertion/Delection (Indels). One indel was found to significantly correlate with CRSwNP and occurred in the promoter region of a bacitracin transport system ATP-binding protein. Additionally, two variants of the highly variable superantigen-like (SSL) proteins were found to significantly correlate with each CRS phenotype. No significant association with other virulence or antibiotic resistance genes were observed, consistent with previous studies.
CONCLUSION: To our knowledge this study is the first to use mGWAS to investigate the contribution of microbial genetic variation to CRS presentations. Utilising the most comprehensive genome-wide analysis methods available, our results suggest that CRS phenotype may be influenced by genetic factors other than specific virulence mechanisms within the S. aureus genome.
Front Cell Infect Microbiol. 2018 Sep 19;8:334. doi: 10.3389/fcimb.2018.00334. eCollection 2018.
Background: With the emergence of the microbiome as an important factor in health and disease in the respiratory tract standardised, validated techniques are required for its accurate characterisation. No standardised technique has been reported specifically for viral sampling in the sinonasal passages. Aim: To optimise viral sampling techniques from the sinonasal cavity. Methods: Sterile cytology brushes were used under endoscopic guidance to sample the sinonasal mucosa at time of endoscopic sinus surgery at both the middle and inferior meatuses (MM and IM). DNA and RNA were extracted from the samples and underwent PCR or RT-PCR testing, respectively, for a panel of 15 common upper respiratory tract viruses. Results: Twenty-four adult patients were recruited for this study. 18/24 (75%) patients were positive for virus in at least one site, while 8/24 (33%) were positive for virus at both sites. The mean number of viruses identified at the two sites were similar (0.875 ± 0.899 at the MM vs. 0.750 ± 1.032 at the IM). 6/24 (25%) of patients showed no virus at either site, while 3/24 (12.5%) demonstrated the same viral species at both sites. Conclusion: Although the number of viruses present at different sites with the nasal cavity are similar, discord exists in the viral species between sites. It is therefore recommended that both sites are sampled in the clinical and research setting better to characterise the viral species within the nasal cavity.
Orbit. 2019 Aug;38(4):308-312. doi: 10.1080/01676830.2018.1518464. Epub 2018 Sep 20.
Purpose: To report a case of a lacrimal sac tumour and describe a prelacrimal approach to the maxillary sinus to excise the nasolacrimal duct in its management. To our knowledge, this approach has not been adapted to remove the nasolacrimal duct for the management of pathological processes involving the nasolacrimal system. Methods: A 58-year-old female patient presented with a 6-month history of epiphora. A lacrimal sac mass was identified, and a biopsy revealed squamous cell carcinoma. Surgical excision was performed via a combined external and endoscopic prelacrimal approach. Results: A prelacrimal approach to the maxillary sinus to excise the nasolacrimal duct in combination with an external approach facilitated an en-bloc excision of the nasolacrimal apparatus. This allowed preservation on the entire inferior turbinate following reconstitution of the lateral nasal wall at the completion of the procedure. Conclusion: The endoscopic endonasal prelacrimal approach to the maxillary sinus is a useful method to approach and excise the nasolacrimal duct in the management of nasolacrimal pathology.
Am J Rhinol Allergy. 2018 Nov;32(6):526-532. doi: 10.1177/1945892418801264. Epub 2018 Sep 19.
BACKGROUND: The Frontal Sinus Masterclass (FSMC) is an effective method for teaching frontal sinus anatomy. A third party developed new software using the same 3-dimensional building block concept. The authors sought to determine whether the use of the software for the educational module yielded similar results to the original FSMC, which used wooden blocks.
METHODS: The study was performed at a sinus course for residents. A precourse test assessed the ability to decipher frontal sinus anatomy prior to the course. Computed tomography (CT) scans of the sinuses were evaluated in triplanar view, and participants attempted to reconstruct the anatomy using the new software. Subsequently, the course instructor explained the anatomy and showed a short corresponding surgical video of the frontal sinusotomy. Cases progressed in anatomical difficulty and inflammatory load. A postcourse test determined knowledge after the course.
RESULTS: In sum, 50 residents completed the pre- and postcourse tests. Overall scores increased from 60.5% to 65.2% ( P = .004). Subanalysis also demonstrated improved ability to locate the frontal drainage pathway from 32.5% to 46% ( P = .011) and label the frontal recess cell structures from 64% to 67.6% ( P = .045).
CONCLUSION: There is minimal literature on proven methods for teaching frontal sinus anatomy. Objectively, participants of the modified FSMC simulation training using new software improved their ability to recognize cells of the frontal recess on CT scans. They especially exhibited better localization of the frontal sinus drainage pathway. Subjectively, participants reported benefit from the course and felt they would be better surgeons.
Sci Rep. 2018 Jul 27;8(1):11325. doi: 10.1038/s41598-018-29765-0.
Infection plays a significant role in the relapse of chronic rhinosinusitis (CRS), however, the role of primary human nasal epithelial cells (HNECs) in this process is largely unknown. Here, we determined the effect of Toll-like receptor (TLR) agonists and inflammatory cytokines on mucosal barrier integrity and immune response of HNECs. TLR 1-9 agonists and inflammatory cytokines were applied to submerged and/or air-liquid interface (ALI) cultures of HNECs from CRS patients and controls for 24 hours. Interleukin-6 (IL-6) protein levels were determined by ELISA. Mucosal barrier integrity was measured via Transepithelial Electrical Resistance and passage of fluorescently-labelled dextrans. IL-1β and IFN- γ significantly increased IL-6 production in HNECs derived from CRS patients and controls, however, a dose-dependent effect was observed in CRS-derived HNECs only. Stimulation with Poly (I:C) LMW induced a 15 to 17 fold increase in IL-6 production by HNEC-ALI control cells (p < 0.05) and HNEC-ALI-CRS cells (p = 0.004) whilst a 2.5 fold increase was observed in CRS HNEC submerged cultures. Priming of cells with Poly (I:C) LMW reduced subsequent IL-6 secretion upon stimulation with TLR 2-4 agonists. Poly (I:C) LMW exerts a potent pro-inflammatory effect on HNECs and reduces a subsequent immune activation by TLR agonists.
Front Microbiol. 2018 May 11;9:917. doi: 10.3389/fmicb.2018.00917. eCollection 2018.
Objectives: Increasing antimicrobial resistance has presented new challenges to the treatment of recalcitrant chronic rhinosinusitis fuelling a continuous search for novel antibiofilm agents. This study aimed to assess the safety and efficacy of Chitogel (Chitogel®, Wellington New Zealand) combined with novel antibiofilm agents Deferiprone and Gallium Protoporphyrin (CG-DG) as a topical treatment against S. aureus biofilms in vivo. Methods: To assess safety, 8 sheep were divided into two groups of 7 day treatments (n = 8 sinuses per treatment); (1) Chitogel (CG) with twice daily saline flush, and (2) CG-DG gel with twice daily saline flush. Tissue morphology was analyzed using histology and scanning electron microscopy (SEM). To assess efficacy we used a S. aureus sheep sinusitis model. Fifteen sheep were divided into three groups of 7 day treatments (n = 10 sinuses per treatment); (1) twice daily saline flush (NT), (2) Chitogel (CG) with twice daily saline flush, and (3) CG-DG gel with twice daily saline flush. Biofilm biomass across all groups was compared using LIVE/DEAD BacLight stain and confocal scanning laser microscopy. Results: Safety study showed no cilia denudation on scanning electron microscopy and no change in sinus mucosa histopathology when comparing CG-DG to CG treated sheep. COMSTAT2 assessment of biofilm biomass showed a significant reduction in CG-DG treated sheep compared to NT controls. Conclusion: Results indicate that CG-DG is safe and effective against S. aureus biofilms in a sheep sinusitis model and could represent a viable treatment option in the clinical setting.
Am J Respir Cell Mol Biol. 2018 Oct;59(4):500-510. doi: 10.1165/rcmb.2017-0415OC.
Matrix metalloproteinase (MMP)-9 is thought to be involved in the etiopathogenesis of chronic rhinosinusitis (CRS) with nasal polyps and cleaves collagen IV, causing hyperpermeability of the basement membrane within mucosal tissue. It is known that MMP-9 expression is negatively affected by sirtuin (SIRT)-1 in human monocytotic cells, retinal endothelial cells, and epithelial carcinoma cells. However, it is unknown which factors affect MMP-9 expression and activity in human nasal epithelial cells (HNECs). To examine factors affecting MMP-9 expression and activity in HNECs, HNECs were stimulated with Toll-like receptor (TLR) agonists, followed by quantitative PCR, immunofluorescence, and zymography to examine MMP-9 expression and activity. MMP-9 expression was evaluated in sinonasal tissue of control subjects without CRS, and patients with CRS without nasal polyps and those with CRS with nasal polyps, in relation to the expression of SIRT1 using a tissue microarray. The effect of SIRT1 stimulation/inhibition on MMP-9 expression in HNECs was also tested. TLR3 agonists increased MMP-9 mRNA expression (473 fold, P = 0.0198) and activity (20.4-fold, P < 0.05). SIRT1 activation or inhibition reciprocally affected MMP-9 expression in the presence of TLR3 agonists. MMP-9 and SIRT1 expression within the epithelial layer of sinonasal tissue was inversely correlated only in patients with CRS but not in control subjects. TLR3 agonists increased MMP-9 expression and activity in HNECs, and the effect was abolished in the presence of SIRT1 activation. SIRT1 and MMP-9 expression was inversely correlated in CRS tissue, supporting SIRT1 as a possible therapeutic target for nasal polyp formation.
Front Microbiol. 2018 Apr 11;9:720. doi: 10.3389/fmicb.2018.00720. eCollection 2018.
Background: The management of recalcitrant chronic rhinosinusitis (CRS) is challenged by difficult-to-treat polymicrobial biofilms and multidrug resistant bacteria. This has led to the search for broad-spectrum non-antibiotic antimicrobial therapies. Colloidal silver (CS) has significant antibiofilm activity in vitro and in vivo against S. aureus, MRSA, and P. aeruginosa. However, due to the lack of scientific efficacy, it is only currently used as an alternative medicine. This is the first study looking at the safety and efficacy of CS in recalcitrant CRS. Methods: Patients were included when they had previously undergone endoscopic sinus surgery and presented with signs and symptoms of sinus infection with positive bacterial cultures. Twenty-two patients completed the study. Patients were allocated to 10-14 days of culture directed oral antibiotics with twice daily saline rinses (n = 11) or 10 days of twice daily 0.015 mg/mL CS rinses (n = 11). Safety observations included pre- and post-treatment serum silver levels, University of Pennsylvania Smell Identification Test (UPSIT) and adverse event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund Kennedy Scores (LKS) and symptom scores using Visual Analog Scale (VAS) and Sino-Nasal Outcome Test (SNOT-22). Results: CS demonstrated good safety profile with no major adverse events, no changes in UPSIT and transient serum silver level changes in 4 patients. CS patients had 1/11 (9.09%) negative cultures, compared to 2/11 (18.18%) in the control group upon completion of the study. Whilst not statistically significant, both groups showed similar improvement in symptoms and endoscopic scores. Conclusion: This study concludes that twice daily CS (0.015 mg/mL) sinonasal rinses for 10 days is safe but not superior to culture-directed oral antibiotics. Further studies including more patients and looking at longer treatment or improving the tonicity of the solution for better tolerability should be explored.
Int Forum Allergy Rhinol. 2018 Apr 6. doi: 10.1002/alr.22127. Online ahead of print.
BACKGROUND: The treatment of the middle turbinate (MT) during endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) remains a contentious issue with arguments both for and against its resection. The purpose of this study was to examine the clinical impact of partial MT resection (PMTR) during ESS, paying particular attention to the risk of developing empty nose syndrome (ENS) and alteration to olfaction.
METHODS: This cohort study was performed on prospectively collected data. A total of 177 patients underwent ESS for CRS; 93 had PMTR and 84 MT preservation (MTP). Preoperative data collection included subjective symptom scores as per the Adelaide Disease Severity Score (ADSS), Lund-Mackay scores, and nasal polyp status. The Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) was administered by telephone consultation and analyzed alongside postoperative symptom scores.
RESULTS: There was no difference in ENS6Q scores in patients who underwent PMTR vs those who had MTP. Patients who underwent PMTR had a higher baseline disease on Lund-Mackay scoring, and were more likely to be nasal polyp patients and be undergoing revision surgery. ADSS scores demonstrated significant improvements in all rhinologic symptoms, with no difference between the cohorts.
CONCLUSION: PMTR is an adjunctive procedure to ESS. This study has established that PMTR as performed by the senior author carries no additional risk of developing ENS symptoms as defined by the ENS6Q, and that it carries no additional risk to olfaction or other rhinologic symptoms. PMTR can be safely considered at time of ESS, especially in patients at risk of lateralization of the MT.
Am J Rhinol Allergy. 2018 Jan 1;32(1):3-6. doi: 10.2500/ajra.2018.32.4496.
BACKGROUND: Recent studies demonstrated that B cells and their chemoattractants are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP). However, the presence of naive B cells and of plasmablasts and memory B-cell subsets in the mucosa and periphery of the same patient with CRS is yet to be characterized.
OBJECTIVE: Here we sought to quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP), and control patients.
METHODS: Polyps, mucosa, and peripheral blood samples were prospectively collected from the patients with CRS and from the non-CRS controls. We used flow cytometry to distinguish among naive, plasmablast, and memory B cells in sinus tissue and peripheral blood.
RESULTS: A total of 45 patients were recruited for the study. The patients with CRSwNP had significantly increased mucosal B-cell numbers versus the controls (3.39 ± 4.05% versus 0.39 ± 1.05% of live cells; p < 0.01, Kruskal-Wallis test), which included naive B cells (0.61 ± 0.94 versus 0.11 ± 0.24% of live cells; p < 0.03, Kruskal-Wallis test), plasmablasts (0.06 ± 0.26 versus 0.00 ± 0.00% of live cells; p < 0.055, Kruskal-Wallis test), and memory B cells (0.62 ± 1.26 versus 0.05 ± 0.15% of live cells; p < 0.02, Kruskal-Wallis test).
CONCLUSION: Our study identified increased frequencies of different B-cell subtypes in the mucosa of patients with CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP had significantly increased B-cell subtypes compared with the patients with CRSsNP and the controls. These results implied a potential role for mucosal B cells in the ongoing inflammation in patients with CRSwNP.
Front Physiol. 2017 Dec 19;8:898. doi: 10.3389/fphys.2017.00898. eCollection 2017.
Background: Recent studies have implied a role for Th17 cells in CRS with nasal polyps (CRSwNP) patients. However, the capacity of these cells to produce Th17 cytokines is still unknown. Here we sought to quantify IL-17A, IL-17F, IL-21, and IL-22 cytokines produced by Th17 cells in mucosal tissue and peripheral blood of CRSwNP, CRS without nasal polyps (CRSsNP) and control patients. Methods: Samples were prospectively collected from CRS patients and non-CRS controls. We used flow cytometry to characterize the Th17 cells and their cytokines in sinonasal tissue and peripheral blood. Results: A total of 36 patients were recruited to the study. CRSwNP patients had significantly more tissue IL-17A (9.53 ± 2.71 vs. 1.11 ± 0.43 vs. 0.77 ± 0.07), IL-17F (4.96 ± 1.48 vs. 0.88 ± 0.31 vs. 0.56 ± 0.04), IL-21 (5.55 ± 2.01 vs. 1.60 ± 0.71 vs. 1.53 ± 0.55) and IL-22 (4.73 ± 1.58 vs. 0.70 ± 0.28 vs. 0.88 ± 0.26) producing Th17 cells compared to CRSsNP and control mucosa per mg of tissue, respectively. Allergic CRSwNP patients had decreased numbers of IL-21 producing Th17 cells compared to non-Allergic CRSwNP. (1.69 ± 0.57 vs. 9.41 ± 3.23) per mg of tissue, respectively (Kruskal-Wallis p < 0.05). Conclusion: In summary our study identified increased numbers of IL-17A, IL-17F, IL-21 and IL-22 positive Th17 cells in CRSwNP patient polyps and peripheral blood suggesting an altered activation state of those cells both locally and systemically. Atopic CRSwNP had decreased amounts of tissue Th17 cell derived IL-21 implying a potential protective role for IL-21 in CRSwNP allergic inflammation.
Am J Rhinol Allergy. 2017 Nov 1;31(6):382-388. doi: 10.2500/ajra.2017.31.4481.
BACKGROUND: A novel, bioabsorbable, fibrinogen-based implant has been developed as a mucosal dressing after endoscopic sinus surgery (ESS). This implant can be formulated with fluticasone propionate (FP) for local elution of corticosteroid to reduce postoperative inflammation and promote mucosal healing.
OBJECTIVE: This study investigated the biocompatibility and pharmacokinetics of the implant in a rabbit model.
METHODS: Implants with and without FP were placed on both intact and demucosalized maxillary sinuses of 33 New Zealand White rabbits. Sinuses with either intact or denuded bone without implants acted as controls. Histopathologic assessments were carried out at 5, 15, and 28 days. Concentrations of FP in the maxillary sinus mucosa, nasal cavity mucosa, and plasma were measured for up to 44 days.
RESULTS: Implants placed on intact mucosa or denuded bone were grossly integrated within 15 days. Minimal foreign body reaction was seen with negligible differences for inflammation, fibrosis, or bone remodeling among controls, sinuses with the implant, or sinuses with the implant plus FP, at all time points. All samples also showed complete or near-complete percentage reepithelialization at 28 days, although the denuded bone controls demonstrated greater percentage reepithelialization at 5 days compared with denuded bone with the implant or implant plus FP (p < 0.0001). The maxillary sinus mucosa demonstrated levels of FP of >140 ng/g up to 44 days. Plasma concentrations of FP were generally very low and were undetectable after day 7.
CONCLUSIONS: The implant and the implant plus FP seemed to be biocompatible in rabbits. The implant plus FP effectively eluted steroid locally over at least 44 days, with negligible plasma concentrations. Further studies are warranted regarding potential therapeutic applications in patients undergoing ESS for chronic rhinosinusitis.
Oral Maxillofac Surg. 2017 Dec;21(4):471-473. doi: 10.1007/s10006-017-0658-6. Epub 2017 Nov 4.
A 53-year-old Afghan man presented with a 12-month history of left proptosis, diplopia and facial swelling 20 years after a bomb blast injury. Magnetic resonance and computed tomography imaging revealed a well-circumscribed lesion centred within the left inferior orbit/superior maxillary sinus along with left orbital fracture. Histopathology and immunostaining of the debulked lesion were consistent with traumatic neuroma of the infraorbital nerve. Infraorbital neuromas have developed following orbital decompression surgeries but have not been reported previously following non-surgical trauma.
Allergy Rhinol (Providence). 2017 Oct 1;8(3):109-117. doi: 10.2500/ar.2017.8.0221.
BACKGROUND: Barosinusitis, or sinus barotrauma, may arise from changes in ambient pressure that are not compensated by force equalization mechanisms within the paranasal sinuses. Barosinusitis is most commonly seen with barometric changes during flight or diving. Understanding and better classifying the pathophysiology, clinical presentation, and management of barosinusitis are essential to improve patient care.
OBJECTIVES: To perform a comprehensive review of the available literature regarding sinus barotrauma.
METHODS: A comprehensive literature search that used the terms "barosinusitis," "sinus barotrauma," and "aerosinusitis" was conducted, and all identified titles were reviewed for relevance to the upper airway and paranasal sinuses. All case reports, series, and review articles that were identified from this search were included. Selected cases of sinus barotrauma from our institution were included to illustrate classic signs and symptoms.
RESULTS: Fifty-one articles were identified as specifically relevant to, or referencing, barosinusitis and were incorporated into this review. The majority of articles focused on barosinusitis in the context of a single specific etiology rather than independent of etiology. From analysis of all the publications combined with clinical experience, we proposed that barosinusitis seemed to fall within three distinct subtypes: (1) acute, isolated barosinusitis; (2) recurrent acute barosinusitis; and (3) chronic barosinusitis. We introduced this terminology and suggested independent treatment recommendations for each subtype.
CONCLUSION: Barosinusitis is a common but potentially overlooked condition that is primed by shifts in the ambient pressure within the paranasal sinuses. The pathophysiology of barosinusitis has disparate causes, which likely contribute to its misdiagnosis and underdiagnosis. Available literature compelled our proposed modifications to existing classification schemes, which may allow for improved awareness and management strategies for barosinusitis.
Int Forum Allergy Rhinol. 2017 Dec;7(12):1170-1177. doi: 10.1002/alr.22021. Epub 2017 Oct 12.
BACKGROUND: Carrageenans have shown to reduce the viral load in nasal secretions and lower the incidence of secondary infections in children with common cold. Despite the widespread use of carrageenans in topical applications, the effect of carrageenans on the sinonasal epithelial barrier has not been elucidated. We investigate the effect of different carrageenans on the sinonasal epithelial barrier and inflammatory response in vitro.
METHODS: Iota and Kappa carrageenan delivered in saline irrigation solutions applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells from chronic rhinosinusitis patients and controls. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER) and immunolocalization of F actin. Ciliary beat frequency (CBF), toxicity, and inflammatory response was studied.
RESULTS: Kappa or Iota carrageenan in the different solutions was not toxic, did not have detrimental effects on epithelial barrier structure and CBF. Rather, application of Kappa carrageenan significantly increased TEER and suppressed interleukin 6 (IL-6) secretion in ALI cultures from CRS patients.
CONCLUSION: Kappa or Iota carrageenan solution was safe and did not negatively affect epithelial barrier function. Kappa carrageenan increased TEER and decreased IL-6 production in CRS patients, indicating positive effects on epithelial barrier function in vitro.
Front Cell Infect Microbiol. 2017 Sep 22;7:418. doi: 10.3389/fcimb.2017.00418. eCollection 2017.
Introduction:Pseudomonas aeruginosa infections are prevalent amongst chronic rhinosinusitis (CRS) sufferers. Many P. aeruginosa strains form biofilms, leading to treatment failure. Lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death. Aim: To assess the activity of a phage cocktail in eradicating biofilms of ex vivo P.aeruginosa isolates from CRS patients. Methods: P. aeruginosa isolates from CRS patients with and without cystic fibrosis (CF) across three continents were multi-locus sequence typed and tested for antibiotic resistance. Biofilms grown in vitro were treated with a cocktail of four phages (CT-PA). Biofilm biomass was measured after 24 and 48 h, using a crystal violet assay. Phage titrations were performed to confirm replication of the phages. A linear mixed effects model was applied to assess the effects of treatment, time, CF status, and multidrug resistance on the biomass of the biofilm. Results: The isolates included 44 strain types. CT-PA treatment significantly reduced biofilm biomass at both 24 and 48 h post-treatment (p < 0.0001), regardless of CF status or antibiotic resistance. Biomass was decreased by a median of 76% at 48 h. Decrease in biofilm was accompanied by a rise in phage titres for all except one strain. Conclusion: A single dose of phages is able to significantly reduce biofilms formed in vitro by a range of P.aeruginosa isolates from CRS patients. This represents an exciting potential and novel targeted treatment for P. aeruginosa biofilm infections and multidrug resistant bacteria.
Laryngoscope. 2018 Jan;128(1):E8-E15. doi: 10.1002/lary.26949. Epub 2017 Oct 10.
OBJECTIVE: Staphylococcus aureus (S. aureus) infection is known to contribute to the severity and recalcitrance of chronic rhinosinusitis (CRS), and its secreted products have been shown to alter the airway barrier. Extracellular proteases secreted by S. aureus are thought to be important in epithelial infection and immune evasion; however, their effect on airway mucosal barrier function is not known.
METHODS: To investigate the impact of extracellular proteases on airway epithelial integrity, the purified S. aureus proteases V8 protease, Staphopain A, Staphopain B, Exfoliative toxin A, and serine protease-like A-F were applied to human nasal epithelial cell air-liquid interface (HNEC-ALI) cultures. Transepithelial electrical resistance (TEER), permeability (Papp) measurements, and immuno-localization of the tight junction proteins claudin-1 and ZO-1 were used to assess barrier integrity. Effects of the proteases on inflammation and cell viability were measured using interleukin-6 (IL-6) ELISA and a lactate dehydrogenase assay.
RESULTS: Application of V8 protease to HNEC-ALI cultures caused a significant concentration and time-dependent decrease in TEER (22.67%, P < 0.0001), a reciprocal Papp increase (20.14-fold, P < 0.05), and a discontinuous ZO-1 immuno-localization compared to control. IL-6 production was significantly reduced in V8 protease-treated cells (153.5 pg/mL, P = 0.0069) compared to control (548.3 pg/mL), whereas no difference in cell viability was observed.
CONCLUSION: S. aureus V8 protease causes dysfunction of mucosal barrier structure and function indicative of a leaky barrier. A reduction in IL-6 levels suggests that the mucosal immunity is impaired by this protease and thus has the potential to contribute to CRS recalcitrance.
LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E8-E15, 2018.
Front Cell Infect Microbiol. 2017 Aug 2;7:344. doi: 10.3389/fcimb.2017.00344. eCollection 2017.
Otitis media with effusion (OME) is a biofilm driven disease and commonly accepted otopathogens, such as Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis, have been demonstrated to form polymicrobial biofilms within the middle ear cleft. However, Alloiococcus otitidis (A. otitidis), which is one of the most commonly found bacteria within middle ear aspirates of children with OME, has not been described to form biofilms. The aim of this study was to investigate whether A. otitidis can form biofilms and investigate the impact on antibiotic susceptibility and survivability in polymicrobial biofilms with H. influenzae in vitro. The ability of A. otitidis to form single-species and polymicrobial biofilms with H. influenzae was explored. Clinical and commercial strains of A. otitidis and H. influenzae were incubated in brain heart infusion with and without supplementation. Biofilm was imaged using confocal laser scanning microscopy and scanning electron microscopy. Quantification of biofilm biomass and viable bacterial number was assessed using crystal violet assays and viable cell counting in both optimal growth conditions and in adverse growth conditions (depleted media and sub-optimal growth temperature). Antimicrobial susceptibility and changes in antibiotic resistance of single-species and multi-species co-culture were assessed using a microdilution method to assess minimal bactericidal concentration and E-test for amoxicillin and ciprofloxacin. A. otitidis formed single-species and polymicrobial biofilms with H. influenzae. Additionally, whilst strain dependent, combinations of polymicrobial biofilms decreased antimicrobial susceptibility, albeit a small magnitude, in both planktonic and polymicrobial biofilms. Moreover, A. otitidis promoted H. influenzae survival by increasing biofilm production in depleted media and at suboptimal growth temperature. Our findings suggest that A. otitidis may play an indirect pathogenic role in otitis media by altering H. influenzae antibiotic susceptibility and enhancing growth under adverse conditions.
Curr Allergy Asthma Rep. 2017 Sep;17(9):59. doi: 10.1007/s11882-017-0726-x.
PURPOSE OF REVIEW: Perturbations in local microbiota have been demonstrated in many chronic inflammatory diseases including chronic rhinosinusitis (CRS). The purpose of this paper is to review the latest microbiome research as it pertains to CRS and establish whether there is any evidence supporting the microbiome hypothesis for CRS. Treatment factors that may influence the sinonasal microbiome as well as the role of probiotics are also discussed.
RECENT FINDINGS: Despite significant heterogeneity in study design, tissue sampling, processing and bioinformatics analysis, consistent findings have emerged from the recent literature. Healthy individuals and CRS patients have similar overall bacterial burden of disease and share many common phylum. CRS patients, however, routinely show reductions in markers of biodiversity. Both medical and surgical treatments appear to influence the sinonasal microbiome, with certain bacterial strains associated with better treatment outcomes. The presence of microbial dysbiosis in CRS is now supported by numerous studies. Whether this dysbiosis is a cause or rather an association of the disease process still remains unclear. Although probiotic therapies show early promise, much larger studies are required to establish their real role as a treatment for CRS.
Rhinology. 2017 Dec 1;55(4):305-311. doi: 10.4193/Rhin16.218.
BACKGROUND: Staphylococcus aureus (S. aureus) can reside within the sinonasal mucosa in chronic rhinosinusitis patients and causes recurrent infections. Within the host cell, S. aureus can evade host immune detection enabling its own survival. We hypothesise that S. aureus can persist within the sinonasal epithelium for a prolonged period without immune activation.
METHODOLOGY: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) undergoing two sinus surgeries were included. Immunohistochemistry and Haematoxylin and Eosin stains were used to determine intracellular S. aureus (ICSA) status and inflammatory cell count, respectively. One-way ANOVA and paired t-tests were performed for comparison between ICSA subgroups and within each subgroup, respectively.
RESULTS: Histopathological specimens from 34 patients (68 procedures) were included. ICSA positivity (ICSA+) was seen in 43 specimens (63.2%) from 26 (76%) patients. 18 (52.9%) of those were ICSA+ in both operations while 8 (23.5%) patients were ICSA+ in only one of the operations. 8 (23.5%) patients were ICSA negative in both operations. There was no difference in the number of eosinophils, lymphocyte and neutrophils between ICSA subgroups.
CONCLUSIONS: This study demonstrated that S. aureus is found intracellularly within CRSwNP tissue at multiple time points without an increase in the number of eosinophils, lymphocytes and neutrophils. This finding supports our hypothesis that ICSA is able to escape from host detection and resides within the sinonasal mucosa despite intense treatment.
Laryngoscope. 2018 Jan;128(1):16-22. doi: 10.1002/lary.26702. Epub 2017 Jul 4.
OBJECTIVE: Next-generation sequencing increases the sensitivity of fungal identification and may improve our understanding of the role that fungi play in sinus health and disease, which remains incompletely understood. We sequenced the internal transcribed spacer (ITS) amplicon to explore the role of the mycobiome in chronic rhinosinusitis (CRS).
METHODS: Swabs were collected intraoperatively from the middle meatus of 90 patients (63 with CRS; 27 controls). DNA was extracted, and ITS amplicon concentration was measured using fluorometry. Internal transcribed spacer amplicons were sequenced on the Illumina MiSeq (Illumina Inc San Diego CA). Sequencing data were analyzed using QIIME.
RESULTS: Using conventional detection techniques of culture and histology, fungi only were identified in nine of 63 (14.3%) CRS patients (fungus-identified group); the remaining 54 CRS patients and all controls did not have fungus identified using the traditional techniques. This fungus-identified group had a significantly higher average ITS concentration and a significantly lower Shannon's diversity index compared to the other two groups. The most abundant organism sequenced was Aspergillus (35.22% of all sequences). Multivariate analysis showed that positive fungal detection using traditional techniques and computed tomography (CT) double densities were the most important clinical predictors of a high fungal biomass, whereas Lund-Mackay score, polyps, eosinophilia, and eosinophilic mucus were not significant in comparison.
CONCLUSION: Fungal biomass estimated through ITS amplicon concentration correlated with traditional fungal detection techniques and CT double densities. Our results suggest that fungal dysbiosis only occurs in the sinuses of a selected subset of patients, and therefore could not be a universal determinant of sinus disease pathogenesis in all CRS patients.
LEVEL OF EVIDENCE: NA. Laryngoscope, 128:16-22, 2018.
Int Forum Allergy Rhinol. 2017 Sep;7(9):916-919. doi: 10.1002/alr.21977. Epub 2017 Jun 28.
BACKGROUND: Crushed autologous muscle is used in skull base surgery in the acute phase of major arterial hemorrhage to stop bleeding. The mechanism of this is not yet clear, but is thought to involve the formation of a platelet plug, which seals the vessel wall defect but still allows ongoing blood flow to the brain.
METHODS: In this study we use flow cytometry to replicate the in-vivo actions of crushed muscle on platelets in whole blood. We compare the ratio of activation of platelets exposed to crushed and uncrushed muscle supernatant in control patients and in patients on antiplatelet agents.
RESULTS: Crushed muscle activated platelets to a higher degree than uncrushed muscle: 5.18-fold greater in control blood (p = 0.002); 6.53-fold greater in aspirin-exposed blood (p < 0.0001); and 9.4-fold greater in clopidogrel-exposed blood (p < 0.0001).
CONCLUSION: Crushed muscle caused a consistently increased ratio of platelet activation when compared with uncrushed muscle across all groups, adding to the evidence that at least part of its clinical effect is the result of platelet activation.
J Neurol Surg B Skull Base. 2017 Jun;78(3):215-221. doi: 10.1055/s-0036-1597277. Epub 2016 Dec 12.
Nano-hemostats are synthetic amino acid chains that self-assemble into a scaffold under certain conditions. These have been shown to be effective in stopping bleeding in small animal models of hemorrhage. Proposed mechanisms for their effect are that they form a mesh analogous to the fibrin plug in native hemostasis and that they may potentiate both platelet activation and the coagulation cascade. These may potentially become valuable adjuncts to endoscopic skull base surgery where there is the potential for both major vessel injury and smaller perforator injury to eloquent areas where bipolar cautery may not be suitable. We present a summary of the clinical studies to date and a small pilot study of nano-hemostat in an endoscopic sheep model of major vessel hemorrhage to determine its efficacy in stopping bleeding in this potentially catastrophic complication.
Int Forum Allergy Rhinol. 2017 Jun;7(6):576-583. doi: 10.1002/alr.21941. Epub 2017 May 8.
BACKGROUND: Major vessel hemorrhage in endoscopic, endonasal skull-base surgery is a rare but potentially fatal event. Surgical simulation models have been developed to train surgeons in the techniques required to manage this complication. This mixed-methods study aims to quantify the stress responses the model induces, determine how realistic the experience is, and how it changes the confidence levels of surgeons in their ability to deal with major vascular injury in an endoscopic setting.
METHODS: Forty consultant surgeons and surgeons in training underwent training on an endoscopic sheep model of jugular vein and carotid artery injury. Pre-course and post-course questionnaires providing demographics, experience level, confidence, and realism scores were taken, based on a 5-point Likert scale. Objective markers of stress response including blood pressure, heart rate, and salivary alpha-amylase levels were measured.
RESULTS: Mean "realism" score assessed posttraining showed the model to be perceived as highly realistic by the participants (score 4.02). Difference in participant self-rated pre-course and post-course confidence levels was significant (p < 0.0001): mean pre-course confidence level 1.66 (95% confidence interval [CI], 1.43 to 1.90); mean post-course confidence level 3.42 (95% CI, 3.19 to 3.65). Differences in subjects' heart rates (HRs) and mean arterial blood pressures (MAPs) were significant between injury models (p = 0.0008, p = 0.0387, respectively). No statistically significant difference in salivary alpha-amylase levels pretraining and posttraining was observed.
CONCLUSION: Results from this study indicate that this highly realistic simulation model provides surgeons with an increased level of confidence in their ability to deal with the rare but potentially catastrophic event of major vessel injury in endoscopic skull-base surgery.
Int Forum Allergy Rhinol. 2017 Jun;7(6):609-614. doi: 10.1002/alr.21924. Epub 2017 Feb 25.
BACKGROUND: The unconventional toll-like receptor (TLR) CD180 is implicated in chronic inflammatory diseases; however, its role in chronic rhinosinusitis (CRS) has yet to be investigated. Here we study the expression of CD180, its homologue TLR4 and myeloid differentiation factor 1 (MD1) on mucosal and systemic immune cell populations in relation to serum immunoglobulin G (IgG) levels.
METHODS: A total of 70 patients were recruited to the study. Mucosal and peripheral blood samples were prospectively collected from CRS patients and non-CRS controls without evidence of sinus disease. The expression of TLR4, MD1, and CD180 was investigated using qualitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and flow cytometry. Serum IgG levels were determined using enzyme-linked immunosorbent assay (ELISA).
RESULTS: CRS with nasal polyps (CRSwNP) patients had significantly increased messenger RNA (mRNA) expression of CD180 and MD1 compared to controls (5.54-fold and 2.1-fold, respectively, p < 0.01). B cells lacking CD180 were lower in CRSwNP tissue compared to CRS without nasal polyps (CRSsNP) and controls (21.07 ± 6.41 vs 41.61 ± 7.82 vs 40.06 ± 8.06; p < 0.01) but higher in blood (39.18 ± 8.3 vs 17.95 ± 7.82 and 12.49 ± 4.92; p ≤ 0.05).
CONCLUSION: Changes in mucosal and peripheral CD180-expressing B cells were identified in CRSwNP patients compared to CRSsNP and controls. This suggests a role for these cells in the dysregulated immune response in these patients.
Case Rep Otolaryngol. 2017;2017:6384586. doi: 10.1155/2017/6384586. Epub 2017 Jan 4.
Klippel-Feil syndrome (KFS) is associated with numerous craniofacial abnormalities but rarely with skull base tumor formation. We report an unusual and dramatic case of a symptomatic, mature skull base teratoma in an adult patient with KFS, with extension through the basisphenoid to obstruct the nasopharynx. This benign lesion was associated with midline palatal and cerebral defects, most notably pituitary and vertebrobasilar arteriolar duplications. A multidisciplinary workup and a complete endoscopic, transnasal surgical approach between otolaryngology and neurosurgery were undertaken. Out of concern for vascular control of the fibrofatty dense tumor stalk at the skull base and need for complete teratoma resection, we successfully employed a tissue resection tool with combined ultrasonic and bipolar diathermy to the tumor pedicle at the sphenoid/clivus junction. No CSF leak or major hemorrhage was noted using this endonasal approach, and no concerning postoperative sequelae were encountered. The patient continues to do well now 3 years after tumor extirpation, with resolution of all preoperative symptoms and absence of teratoma recurrence. KFS, teratoma biology, endocrine gland duplication, and the complex considerations required for successfully addressing this type of advanced skull base pathology are all reviewed herein.
Front Cell Infect Microbiol. 2016 Dec 26;6:187. doi: 10.3389/fcimb.2016.00187. eCollection 2016.
Background:Staphylococcus aureus (S. aureus) small colony variants (SCVs) can survive within the host intracellular milieu and are associated with chronic relapsing infections. However, it is unknown whether host invasion rates and immune responses differ between SCVs and their wild-type counterparts. This study used a stable S. aureus SCV (WCH-SK2SCV) developed from a clinical isolate (WCH-SK2WT) in inflammation-relevant conditions. Intracellular infection rates as well as host immune responses to WCH-SK2WT and WCH-SK2SCV infections were investigated. Method: NuLi-1 cells were infected with either WCH-SK2WT or WCH-SK2SCV, and the intracellular infection rate was determined over time. mRNA expression of cells infected with each strain intra- and extra-cellularly was analyzed using a microfluidic qPCR array to generate an expression profile of thirty-nine genes involved in the host immune response. Results: No difference was found in the intracellular infection rate between WCH-SK2WT and WCH-SK2SCV. Whereas, extracellular infection induced a robust pro-inflammatory response, intracellular infection elicited a modest response. Intracellular WCH-SK2WT infection induced mRNA expression of TLR2, pro-inflammatory cytokines (IL1B, IL6, and IL12) and tissue remodeling factors (MMP9). In contrast, intracellular WCH-SK2SCV infection induced up regulation of only TLR2. Conclusions: Whereas, host intracellular infection rates of WCH-SK2SCV and WCH-SK2WT were similar, WCH-SK2SCV intracellular infection induced a less widespread up regulation of pro-inflammatory and tissue remodeling factors in comparison to intracellular WCH-SK2WT infection. These findings support the current view that SCVs are able to evade host immune detection to allow their own survival.
Int Forum Allergy Rhinol. 2017 Apr;7(4):332-337. doi: 10.1002/alr.21893. Epub 2016 Dec 5.
BACKGROUND: The frontal sinus is considered the most challenging sinus to address surgically. There are no current classifications of the degree of surgical complexity of different frontal sinus configurations. The aim of this study is to develop a classification system of the degree of complexity of frontal recess surgery based on preoperative computed tomography (CT) scans.
METHODS: Authors were asked to submit a classification system. These were circulated to all authors. Selection of the final 3 classifications was based on a majority consensus. These classifications were compared further for time-taken, ease-of-use, and interrater agreement. These were assessed by the authors on 10 CT scans representing a range of anticipated surgical difficulty.
RESULTS: Out of 3 compared classifications, classification A was the quickest to score (1.44 minutes vs 1.57 minutes and 2.25 minutes), subjectively easiest (3.23 vs 4.07 and 5 on a visual analogue scale [VAS]), and had a moderate interrater agreement (0.52 vs 0.42 and 0.79). In addition, the grading of complexity was as good whether measurements were taken on the CT scans or whether size of the frontal ostium was visually estimated.
CONCLUSION: We propose a fast, easy classification to anticipate the complexity of surgery in the frontal sinus and recess, for patients undergoing primary surgery.
JAMA Otolaryngol Head Neck Surg. 2017 Feb 1;143(2):155-161. doi: 10.1001/jamaoto.2016.3105.
IMPORTANCE: The adenoid pad has long been considered a reservoir for bacteria in the pathogenesis of otitis media with effusion (OME). However, bacteria more reminiscent of external auditory canal (EAC) commensals are often demonstrated within middle ear aspirates.
OBJECTIVE: To compare the microbiota of the EAC, the middle ear with OME, and the adenoid pad to further clarify the true source of middle ear bacteria.
DESIGN, SETTING, AND PARTICIPANTS: Middle ear fluid (MEF) aspirates and EAC lavages were collected from 18 children with OME undergoing ventilation tube insertion from June 1, 2014, to August 31, 2015, at Women and Children's Hospital, Adelaide, Australia. Adenoid pad and MEF samples were included from a previous study. Samples were analyzed using sequencing of the 16S ribosomal RNA gene. Previously collected microbiota data from the adenoid pad were collated for analysis.
MAIN OUTCOME MEASURES: Mean relative abundance of top bacterial genera for the MEF, EAC, and adenoid pad samples.
RESULTS: Eighteen pediatric patients with chronic OME (6 female; 12 male; mean [SD] age, 48  months) were recruited prospectively, with 34 paired MEF and EAC samples. The MEF microbiota (mean relative abundance [SD]) consisted of Alloiococcus otitidis (37.5% [40.0%]), Haemophilus (14.4% [29.1%]), Moraxella (10.0% [26.4%]), Staphylococcus (8.2% [21.9%]), and Streptococcus (3.8% [13.1%]). The mean relative abundance (SD) microbiota of the EAC demonstrated a sparsity of classic otopathogens, including Haemophilus (0.3% [0.8%]), Moraxella (0.3% [0.7%]), and Streptococcus (0.2% [0.6%]), but had a high abundance of Alloiococcus (58.0% [44.1%]), Staphylococcus (20.8% [34.0%]), and Pseudomonas (3.2% [17.1%]). In contrast, based on previously collected data, the microbiota of the adenoid pad showed a high abundance of the classic otopathogens with a sparsity of EAC genera for Alloiococcus (0.1% vs 28.9%, respectively; P < .001), Haemophilus (25.2% vs 18.2%, respectively; P = .002), Staphylococcus (0.2% vs 10.8%, respectively; P = .02), Streptococcus (12.7% vs 4.2%, respectively; P < .001), and Pseudomonas (0 vs 2.1% respectively; P < .001). The microbiota of the MEF collected during 2 consecutive years were similar (Alloiococcus, 22.7% vs 37.5%; Haemophilus, 22.5% vs 14.0%; Staphylococcus, 10.9% vs 10.7%; Moraxella, 5.0% vs 9.7%; Corynebacteria, 6.2% vs 3.1%; Streptococcus, 4.8% vs 3.7%; and Pseudomonas, 1.1% vs 3.0%; P ≥ .05).
CONCLUSIONS AND RELEVANCE: The EAC and the nasopharynx could serve as reservoirs for microbiota of the middle ear. Furthermore, the microbiota of the middle ear with effusion appear to be relatively stable over time and between populations with OME.
Int Forum Allergy Rhinol. 2017 Jan;7(1):80-86. doi: 10.1002/alr.21845. Epub 2016 Aug 31.
BACKGROUND: The impact of failed cerebrospinal fluid leak (CSF) leak repair in endoscopic skull base surgery has not been adequately studied.
METHODS: In this investigation we reviewed patients who had undergone endoscopic skull base surgery between 2002 and 2014 at 7 international centers. Demographic variables, comorbidities, tumor characteristics, and repair techniques were evaluated to determine association with successful repair of CSF leak. Postoperative complications and length of stay were compared among groups.
RESULTS: Data were collected on 2097 patients who were divided into 3 groups: (1) those with no intraoperative leak (n = 1533); (2) those with successful repair of their intraoperative leak (n = 452); and (3) those with failed repair (n = 112). Compared with successful repair, failed repair was associated with an increased risk of intracranial infection (odds ratio [OR], 5.6; 95% confidence interval [CI], 5.3-13.15), pneumocephalus (OR, 16; 95% CI, 5.8-44.4), 30-day readmission (OR, 8.4; 95% CI, 5.3-13.5), reoperation (OR, 115.4; 95% CI, 56.3-236.8), and prolonged hospital stay (14.9 vs 7.0 days, p < 0.01). Outcomes in patients who had successful repairs of intraoperative leaks were similar to those who never had leakage. Intraoperative use of pedicled nasoseptal flaps was associated with successful repair (OR, 0.60; 95% CI, 0.34-0.92).
CONCLUSION: Intraoperative CSF leaks are a frequent and expected occurrence during endoscopic skull base surgery. Failed CSF leak repair has a significant impact on patient outcomes, with increased rates of postoperative pneumocephalus, intracranial infections, reoperation, deep vein thrombosis, readmission, and prolonged hospital stay. Recognition and repair of intraoperative CSF leaks reduces postoperative complications. Use of pedicled nasoseptal flaps improves outcomes in reconstructing defects at higher risk for postoperative leak.
Int Forum Allergy Rhinol. 2016 Nov;6(11):1117-1125. doi: 10.1002/alr.21783. Epub 2016 Aug 23.
BACKGROUND: In patients undergoing transnasal endoscopic sellar surgery, an analysis of risk factors and predictors of intraoperative and postoperative cerebrospinal fluid leak (CSF) would provide important prognostic information.
METHODS: A retrospective review of patients undergoing endoscopic sellar surgery for pituitary adenomas or craniopharyngiomas between 2002 and 2014 at 7 international centers was performed. Demographic, comorbidity, and tumor characteristics were evaluated to determine the associations between intraoperative and postoperative CSF leaks. Correlations between reconstructive and CSF diversion techniques were associated with postoperative CSF leak rates. Odds ratios (OR) were identified using a multivariate logistic regression model.
RESULTS: Data were collected on 1108 pituitary adenomas and 53 craniopharyngiomas. Overall, 30.1% of patients had an intraoperative leak and 5.9% had a postoperative leak. Preoperative factors associated with increased intraoperative leaks were mild liver disease, craniopharyngioma, and extension into the anterior cranial fossa. In patients with intraoperative CSF leaks, postoperative leaks occurred in 10.3%, with a higher postoperative leak rate in craniopharyngiomas (20.8% vs 5.1% in pituitary adenomas). Once an intraoperative leak occurred, craniopharyngioma (OR = 4.255, p = 0.010) and higher body mass index (BMI) predicted postoperative leak (OR = 1.055, p = 0.010). In patients with an intraoperative leak, the use of septal flaps reduced the occurrence of postoperative leak (OR = 0.431, p = 0.027). Rigid reconstruction and CSF diversion techniques did not impact postoperative leak rates.
CONCLUSION: Intraoperative CSF leaks can occur during endoscopic sellar surgery, especially in larger tumors or craniopharyngiomas. Once an intraoperative leak occurs, risk factors for postoperative leaks include craniopharyngiomas and higher BMI. Use of septal flaps decreases this risk.
Laryngoscope. 2016 Dec;126(12):2844-2851. doi: 10.1002/lary.26128. Epub 2016 Jun 23.
OBJECTIVES/HYPOTHESIS: The adenoid pad has been considered a reservoir for bacteria in the pathogenesis of otitis media with effusion. This study aimed to characterize the middle ear microbiota in children with otitis media with effusion and establish whether a correlation exists between the middle ear and adenoid microbiota.
STUDY DESIGN: Prospective, controlled study.
METHODS: Middle ear aspirates adenoid pad swabs were collected from 23 children undergoing ventilation tube insertion. Adenoid swabs from patients without ear disease were controls. Samples were analyzed using 16S rRNA sequencing on the Illumina MiSeq platform.
RESULTS: Thirty-five middle ear samples were collected. The middle ear effusion microbiota was dominated by Alloiococcus otitidis (23% mean relative abundance), Haemophilus (22%), Moraxella (5%), and Streptococcus (5%). Alloiococcus shared an inverse correlation with Haemophilus (P = .049) and was found in greater relative abundance in unilateral effusion (P = .004). The microbiota of bilateral effusions from the same patient were similar (P < .001). However, the otitis media with effusion microbiota were found to be dissimilar to that of the adenoid (P = .01), whereas the adenoid microbiota of otitis media with effusion and control patients were similar (P > .05) (permutational multivariate analysis of the variance).
CONCLUSIONS: Dissimilarities between the local microbiota of the adenoid and the middle ear question the theory that the adenoid pad is a significant reservoir to the middle ear in children with otitis media with effusion. A otitidis had the greatest cumulative relative abundance, particularly in unilateral effusions, and shares an inverse correlation with the relative abundance of Haemophilus.
LEVEL OF EVIDENCE: NA Laryngoscope, 126:2844-2851, 2016.
Allergy Rhinol (Providence). 2016 Jan;7(1):50-4. doi: 10.2500/ar.2016.7.0142.
OBJECTIVE: In this report, we present a rare case of avascular necrosis (AVN) in an otherwise healthy 42-year-old male patient treated with low dose oral corticosteroids for his bronchitis. A systematic review of the literature related to AVN and corticosteroids was performed.
CASE REPORT: Forty-two-year-old male with no underlying conditions predisposing him to AVN who had been treated four years before for chronic bronchitis with two courses of oral prednisone therapy presented with bilateral AVN of the hips.
METHODS: An OVID database search of the terms "low total dose," "corticosteroids," and "avascular necrosis" was performed. Two PubMed searches of various permutations of "low-dose," "corticosteroids," "avascular necrosis," and "osteonecrosis" were also performed. Results were then narrowed to relevant articles.
RESULTS: Median total dose of oral corticosteroids in patients with AVN in reviewed articles was 981 mg, with lowest reported association at 105 mg. Median duration of therapy was 16 days with shortest course of six days.
CONCLUSION: There is emerging data linking AVN with corticosteroid doses previously thought to be safe. After reviewing the relevant literature, it is our consensus to inform all patients regarding AVN before oral corticosteroid use.
Int Forum Allergy Rhinol. 2016 Aug;6(8):792-9. doi: 10.1002/alr.21758. Epub 2016 Apr 15.
BACKGROUND: Staphylococcus aureus (S. aureus) has been shown to exist within nasal epithelial cells in chronic rhinosinusitis (CRS) patients. This study investigates the localization of intracellular S. aureus (ICSA) in CRS patients, the associated histopathology changes, and their effect on long-term postoperative outcomes.
METHODS: A prospective study of patients with CRS with and without polyps and control patients (n = 25, 15, and 8, respectively) undergoing endoscopic sinus surgery was performed. Validated patient reported symptom scores and objective endoscopic scores were collected preoperatively and 12 months postoperatively. Mucosal tissue samples were collected and examined for the presence of ICSA using immunohistochemical analysis. Tissue also underwent routine hematoxylin and eosin and Sirius Red staining to evaluate the inflammatory cell load and extent of fibrosis.
RESULTS: ICSA appeared to localize to the perinuclear region of the pseudostratified columnar respiratory epithelium. ICSA was more prevalent in CRS without nasal polyps (CRSsNP) than in CRS with nasal polyps (CRSwNP) or controls (80% vs 56% vs 38%, respectively). ICSA positive status did not appear to influence symptom or endoscopic scores at the time of surgery nor 12 months postoperatively. Lymphocytes and total inflammatory cells were significantly increased in ICSA(+) group than ICSA(-) groups (36.4 vs 22.4 cells/area and 53.8 vs 29.1 cells/area, respectively). There was no difference found in fibrosis.
CONCLUSION: This study indicated that ICSA was most prevalent in CRSsNP patients and was associated with increased lymphocytia and total inflammatory cells but not with worse symptomatology, endoscopy results, or basement membrane (BM) thickening.
Ann Otol Rhinol Laryngol. 2016 Aug;125(8):613-21. doi: 10.1177/0003489416641429. Epub 2016 Apr 7.
OBJECTIVE: Microbiomics in chronic diseases, including chronic rhinosinusitis (CRS), have undergone rapid advances in recent times. The introduction of Next Generation Sequencing (NGS) technology has produced significant clinical insights regarding the bacteriology of these conditions. We review studies that have used 16S rRNA sequencing to specifically investigate the microbiota profiles of patients with CRS in a variety of contexts.
METHODS: Literature review using the CINAHL, MEDLINE, PUBMED, and the Cochrane databases. Papers utilizing 16S-sequencing technology on CRS specimens published between January 1, 1995, and October 31, 2015, were included. Studies limited to only healthy controls were excluded.
RESULTS: Consistent with published studies using non-NGS techniques, the main genera commonly identified from the sinuses of CRS patients included Staphylococcus, Propionibacterium, and Corynebacterium. The microbiome of CRS patients had lower bacterial diversity compared to controls in a number of studies. Also consistent with non-NGS-based studies, Staphylococcus was implicated as an important genus, with highly colonized patients having worse surgical outcomes. Conflicting reports of antibiotic effects on the CRS microbiome were observed. Sampling methods were well investigated, many of the studies reviewed failed to include important methodological detail.
CONCLUSION: While 16S sequencing is a novel microbiological laboratory method, current studies have confirmed our existing understanding of bacteriology of CRS without providing significant additional clinical insight. Complementing 16S studies with more complex NGS methods while developing robust clinical studies aimed at shifting the disrupted CRS microbiome will provide researches with the opportunity to derive further clinical insight and develop new therapeutic targets.
Int Forum Allergy Rhinol. 2016 Aug;6(8):826-34. doi: 10.1002/alr.21742. Epub 2016 Mar 25.
BACKGROUND: Chronic rhinosinusitis (CRS) is categorized into 2 types based on the absence (CRSsNP) and presence of nasal polyps (CRSwNP). Although CRSsNP patients lack nasal polyps, the mucosa may show variable degrees of polypoid change. This raises the question of whether or not the classification system is an over simplification and that CRSsNP and CRSwNP only represent 2 phenotypic extremes along a broader spectrum of immunologically different disease processes. To investigate this, adaptive and innate immune cells were compared in the different tissue types within CRSsNP and CRSwNP patients.
METHODS: Tissue from 15 CRSwNP, 6 CRSsNP, and 8 healthy control patients was obtained prospectively. Nonpolypoid mucosa, polypoid tissues, and polyps were obtained at the time of endoscopic sinus surgery and analyzed using flow cytometry for various adaptive and innate immune cell subsets.
RESULTS: In the polyps from CRSwNP patients there were significantly more T regulatory (Treg) cells (12.86 ± 12.60 vs 2.83 ± 4.68) and Th17 cells (16.12 ± 11.75 vs 2.31 ± 2.13) compared to the polypoid tissue from CRSsNP patients. Cellular infiltrates in the nonpolypoid or polypoid mucosa of the different patient categories showed no difference in CRSwNP, CRSsNP and control groups.
CONCLUSION: This observational study identified an increase in Treg and Th17 cells in CRSwNP patients implying that these cells may be implicated in polyp development. Importantly it also identified a similar inflammatory infiltrate in nonpolyp or polypoid mucosa across control, CRSsNP, and CRSwNP groups inferring that polyps should be sampled when studying CRSwNP.
Int Forum Allergy Rhinol. 2016 Aug;6(8):820-5. doi: 10.1002/alr.21739. Epub 2016 Mar 14.
BACKGROUND: Patients with aspirin-exacerbated respiratory disease (AERD) and chronic rhinosinusitis with nasal polyps (CRSwNP) are often reported to be recalcitrant to standard medical and surgical intervention. Failure rates of standard endoscopic sinus surgery in these patients are reported to be as high as 90%. We review the outcomes for our cohort of AERD patients undergoing endoscopic sinus surgery and endoscopic modified Lothrop procedure (EMLP).
METHODS: Data was collected prospectively between January 2001 and December 2013. Information including demographics, asthma status, aspirin sensitivity, 22-item Sino-Nasal Outcome Test (SNOT-22), Lund-Mackay scores, and endoscopic ostium assessment were collected for up to 5 years. Minimum follow-up was 6 months.
RESULTS: A total of 31 AERD patients underwent complete sphenoethmoidectomy, maxillary antrostomy and EMLP during the study period with an average follow-up of 36 months. Polyp recurrence was seen in a total of 18 patients (58%). Seven patients required revision EMLP following initial surgery demonstrating a failure rate of 22.5%. AERD patients had a statistically significant increased risk of both nasal polyps recurrence and need for revision surgery. Revision EMLP was needed due to recurrence of nasal polyps in 6 cases and frontal ostium stenosis in a single case. Time to revision EMLP was similar between the groups.
CONCLUSION: Complete sphenoethmoidectomy, maxillary antrostomy, and EMLP is successful in a significant majority of patients with AERD and CRSwNP. It is well tolerated with a low complication rate and facilitates successful ongoing medical management of the condition in patients with AERD.
Int Forum Allergy Rhinol. 2016 Jul;6(7):677-96. doi: 10.1002/alr.21738. Epub 2016 Mar 14.
The frontal recess and frontal sinus anatomy can vary from simple to complex. The variations in the anatomy of the frontal recess and frontal sinus are considerable but almost all variations can be classified if the various cell patterns are analyzed. This consensus document was developed to improve the ability of the surgeon to understand these possible variations, plan the surgery, and communicate these complexities when teaching or reporting outcomes. Once the surgeon understands the anatomical pattern of the frontal sinus and recess cells, the extent of surgery can be planned. This document presents a classification of the extent of surgery based on the anatomical classification.
Ear Nose Throat J. 2016 Mar;95(3):E19-27.
Respiratory epithelial adenomatoid hamartoma (REAH) is a rare benign lesion that affects the nasal cavity and paranasal sinuses. We present 4 cases of REAH that involved the olfactory clefts; 1 case was bilateral. Each of the cases was treated surgically, and no recurrence was observed. Most reports have indicated that REAH occurs in the presence of sinonasal inflammation, particularly nasal polyposis, yet all 4 of our cases occurred in the absence of concurrent rhinosinusitis. This suggests that the etiology of REAH is multifactorial. In addition, we review the literature on REAH, and we discuss its presentation, differential diagnosis, radiology, histopathology, and underlying treatment principles.
Int Forum Allergy Rhinol. 2016 Feb;6 Suppl 1:S22-209. doi: 10.1002/alr.21695.
BACKGROUND: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS).
METHODS: Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus.
RESULTS: The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS.
CONCLUSION: As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.
Int Forum Allergy Rhinol. 2016 May;6(5):518-22. doi: 10.1002/alr.21715. Epub 2016 Feb 16.
BACKGROUND: Endoscopic modified Lothrop procedure (EMLP) is used to treat patients who fail conventional sinus surgery. The failure rate of a primary EMLP is reported to be between 5% and 32%. The failure rate of revision EMLP has not been reported. We present our institutions data regarding the outcome of patients requiring revision EMLP.
METHODS: Data was collected prospectively. Patients undergoing primary EMLP between January 2001 and December 2013 with a minimum follow-up of 6 months were included. Information related to demographics, asthma status, aspirin sensitivity, 22-item Sino-Nasal Outcome Test (SNOT-22) score, Lund-Mackay scores, intraoperative findings, and endoscopic ostium assessment were collected.
RESULTS: There were 213 primary EMLPs completed with average follow-up of 36 months. The failure rate of primary EMLP was 8.9% (19/213), whereas the failure rate of revision EMLP was 21% (4/19). Risk factors for failure of primary EMLP included the presence of intraoperative pus, more than 5 previous sinus operations and aspirin-exacerbated respiratory disease (AERD). Revision of EMLP was undertaken primarily due to recurrence of nasal polyps or ostium stenosis. Those patients who underwent revision EMLP experienced symptomatic improvement and no major complications following the procedure.
CONCLUSION: The failure rate of revision EMLP is 21% in our series. The majority of revisions were for nasal polyp recurrence. Revision EMLP is a safe and well-tolerated procedure in the small group of patients that require further surgery. Patients with intraoperative pus present at their initial EMLP, more than 5 previous sinus operations, or AERD are at increased risk of failure.
Curr Opin Otolaryngol Head Neck Surg. 2016 Feb;24(1):26-30. doi: 10.1097/MOO.0000000000000222.
PURPOSE OF REVIEW: Optimization of the surgical field involves a complex interplay of many factors. Although it is agreed that hemostasis is critical to safe, efficient, and successful sinus surgery, a lack of consensus exists as to the best way to achieve it. This review examines the current body of evidence supporting many of the practices surgeons believe to influence hemostasis.
RECENT FINDINGS: Although many of the practices discussed in this article have long been considered to influence hemostasis, it is not until recently that high-level evidence supporting their use has been available. Well designed studies now exist supporting the preoperative use of oral steroids in polyp patients, the importance of adequate reverse trendelenburg positioning, the use of flexible laryngeal mask ventilation during general anesthesia, and the increased safety and comparable efficacy of topical epinephrine over other topical and injectable agents. Controversy still exists as to the ideal method of achieving controlled hypotensive anesthesia, although new evidence has emerged as to what hemodynamic parameters should be adhered to, to reduce the risk of cerebral hypoperfusion.
SUMMARY: Numerous factors influence hemostasis and so it is important that ENT surgeons have a sound understanding of the evidence supporting their everyday surgical practice. Improved standardization of scoring and reporting of bleeding may increase the power of research studies to draw more definitive conclusions about the role that certain factors have on hemostasis.
J Midwifery Womens Health. 2015 Nov-Dec;60(6):674-81. doi: 10.1111/jmwh.12350. Epub 2015 Nov 30.
This article examines the history and present state of the midwife as laborist. The role of the midwife and obstetrician laborist/hospitalist is rapidly evolving due to the need to improve patient safety and provide direct care due to reduced resident work hours, as well as practice demands experienced by community providers and other factors. Models under development are customized to meet the needs of different communities and hospitals. Midwives are playing a prominent role in many laborist/hospitalist practices as the first-line hospital provider or as part of a team with physicians. Some models incorporate certified nurse-midwives/certified midwives as faculty to residents and medical students. The midwifery laborist/hospitalist practices at Baystate Medical Center in Springfield, Massachusetts, are presented as an example of how midwives are functioning as laborists. Essential components of a successful midwife laborist program include interdisciplinary planning, delineation of problems the model should solve, establishment of program metrics, clear practice guidelines and role definitions, and a plan for sustained funding. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health.
Int Forum Allergy Rhinol. 2016 Jan;6(1):101-7. doi: 10.1002/alr.21622. Epub 2015 Aug 6.
BACKGROUND: The goal of this study was to identify preoperative risk factors associated with increased perioperative morbidity after endoscopic pituitary surgery.
METHODS: A retrospective review of patients undergoing endoscopic pituitary adenoma surgery between 2002 and 2014 at 6 international centers was performed. Standard demographic and comorbidity data, as well as information regarding tumor extent and treatment were collected. Logistic regression was used to examine risk factors for the following 30-day outcomes: systemic complications, intracranial complications, postoperative cerebrospinal fluid (CSF) leaks, length of hospital stay, readmission, and reoperation.
RESULTS: Data was collected on 982 patients with a mean age of 52 years. The median body mass index (BMI) for all patients was 30.9 kg/m(2) with 56% female. The median hospital stay was 5 days and 23.8% of patients suffered a postoperative adverse event. Systemic complications occurred in 3.2% of patients and intraventricular extension was a risk factor (odds ratio [OR] 8.9). Intracranial complications occurred in 7.3% of patients and risk factors included previous radiation (OR 8.6) and intraventricular extension (OR 7.9). Reoperation occurred in 6.5% of patients and intraventricular extension (OR 7.3) and age (<40 years, OR 3.5; 40 to 64 years, OR 3.2) were risk factors. Postoperative CSF leaks occurred in 5.5% of patients and risk factors included female gender (OR 2.4), BMI ≥ 30 (OR 2.1), age (<40 years, OR 5.3; 40 to 64 years, OR, 7.9), and intraventricular extension (OR, 9.5).
CONCLUSION: Postoperative endoscopic pituitary adenoma surgery complications are associated with tumors with intraventricular extension, preoperative radiation, as well as common patient comorbidities. Identification of these factors may permit implementation of strategies to reduce postoperative complications.
Int Forum Allergy Rhinol. 2015 Aug;5(8):667-73. doi: 10.1002/alr.21533. Epub 2015 May 7.
BACKGROUND: Treatment indications for recurrent acute rhinosinusitis (RARS) remain poorly defined. We studied outcomes of medical vs surgical treatment of RARS, anatomic variants associated with RARS, and factors predicting crossover from medical to surgical treatment.
METHODS: A total of 220 RARS patients treated between 2006 and 2014 were retrospectively divided into 3 cohorts: medical only (MED); surgical only (SURG); or medical crossing over into surgical (CROSS). Twenty-two item Sino-Nasal Outcome Test (SNOT-22) scores, modified Lund-Kennedy endoscopy scores, and prevalence of anatomic variants by computed tomography (CT) were compared. A total of 220 CT scans obtained for non-sinus indications served as controls. A logistic regression model was used for analysis.
RESULTS: The mean baseline SNOT-22 scores for all cohorts were similar (MED = 48, SURG = 49, CROSS = 45, p < 0.0001). The SURG cohort showed greater reduction of SNOT-22 scores compared to the MED cohort at 3, 6, and 12 months follow-up (p < 0.0001). The crossover cohort converted to surgery after escalation of SNOT-22 score by a mean of 15 points (p < 0.03), and showed significant reduction postoperatively (p < 0.0001). Haller cell (odds ratio [OR] 3.9; p < 0.0001), concha bullosa (OR 3.7; p < 0.003), and accessory ostium (OR 2.2; p < 0.01) were more common in the entire RARS group vs controls; however, there were no inter-cohort differences in prevalence.
CONCLUSION: RARS patients can benefit from both medical and surgical treatment strategies, but surgical treatment results in greater symptomatic improvement compared to medical treatment. Patients cross over from medical to surgical treatment when SNOT-22 scores escalate by a mean of 15 points. Haller cell, concha bullosa, and accessory ostium are associated with RARS but are equally common in medical, surgical, and crossover cohorts.
Orbit. 2015 Jun;34(3):142-5. doi: 10.3109/01676830.2015.1014509. Epub 2015 Apr 22.
PURPOSE: To assess the frequency of concomitant adjunctive nasal procedures performed in powered endoscopic dacryocystorhinostomy (DCR).
METHODS: Retrospective review of 269 consecutive powered endoscopic DCR's performed in 202 patients over a period of 10 years from 2003 to 2013. Patient records were reviewed for demographic data, clinical profiles and surgical notes. Concomitant adjunctive procedures were studied with relation to number of patients, indications, types of procedures (septoplasty, middle turbinoplasty and functional endoscopic sinus surgery or FESS) and complications.
RESULTS: 269 powered endoscopic DCR's were performed on 202 patients. The mean age at surgery was 58.4 years (range 20-91 years). Adjunctive nasal procedures were performed in 53.4% (108/202) of the patients. 47% (95/202) required a septoplasty. Among the 95 septoplasty patients, 85 required solo septoplasty and 10 had additional sinus procedure. Middle turbinoplasty was performed in 5.9% (12/202) and septal papilloma excision was performed in 0.49% (1/202). No additional morbidity was noticed with adjunctive procedures. Successful outcomes of DCR were achieved in 96.5% of patients.
CONCLUSION: Simultaneous adjunctive nasal procedures were commonly required with powered endoscopic DCR. Septoplasty and middle turbinoplasty when performed as needed, provides an additional access to lacrimal region and may facilitate successful outcomes.
Orbit. 2015 Jun;34(3):146-51. doi: 10.3109/01676830.2015.1014510. Epub 2015 Apr 22.
AIM: Ostium granulomas following dacryocystorhinostomy (DCR) have not been studied in detail previously. This study aims to classify the DCR-related granulomas based on their ostial locations and to assess the outcomes of their management.
METHODS: A retrospective consecutive case series of 47 ostial granulomas evaluated over a period of 2 years were included in this study. All patients underwent detailed endoscopic examination to assess the granuloma locations and their response to initial topical steroids treatment. Persistent granulomas either underwent further management with excision or intralesional steroids based on their location. Patients were followed up for a minimum of 6 months. The primary outcome measure was resolution of granuloma.
RESULTS: The mean age at presentation was 45 years with a female preponderance (68%). 70% (33/47) of granulomas were following external DCR and 30% (14/47) occurred in the setting of endonasal DCR. The most common location was an edge granuloma in 46.8% (22/47) followed by a combined granuloma in 21.2% (10/47). 91.4% (43/47) underwent initial treatment with topical nasal steroids. The remaining 4 (8.5%) underwent primary excision. Among those treated with topical steroids (n = 43), 9.3% (4/43) underwent further treatment with intralesional triamcinolone. Overall, 4.2% (2/47) recurred in 6 weeks following resolution and were treated with excision.
CONCLUSION: We recommend routine endoscopic evaluation of all the DCR ostia. Detection of granulomas in early stages and appropriate management as per guidelines proposed may aid in better outcomes.
JAMA Otolaryngol Head Neck Surg. 2015 Jun;141(6):562-5. doi: 10.1001/jamaoto.2015.0524.
IMPORTANCE: Orbital compartment syndrome is an acute rise in intraorbital volume resulting in increased intraorbital pressure and possible ischemic compromise of the optic nerve. Tonometric pressure measurement of intraocular pressure can aid surgeons in the diagnosis of this condition and in choosing the need to proceed with emergent surgical intervention. In addition, we present an unexpected cause of orbital compartment syndrome following routine frontal sinus irrigation.
OBSERVATIONS: An emergent lateral canthotomy and cantholysis followed by endoscopic medial wall decompression were performed, with intraocular pressure measurements performed throughout the evolution of this successful, and vision sparing, set of procedures. The techniques and continuous improvements in intraocular pressure measurements are described.
CONCLUSIONS AND RELEVANCE: There are only rare reports of the progression of intraocular pressure prior to, and concurrent with, surgical orbital decompression. While no absolute threshold for intraocular pressure exists for when surgical decompression should be performed, the decision of when and which decompression procedures to undertake should be based on clinical judgment and experience. Availability of tonometry in the operating room serves to measure response to management in these rare but challenging settings where intervention may be required to prevent irreversible visual loss.
PLoS One. 2015 Apr 14;10(4):e0123216. doi: 10.1371/journal.pone.0123216. eCollection 2015.
BACKGROUND: The role of the sino-nasal microbiome in CRS remains unclear. We hypothesized that the bacteria within mucosal-associated biofilms may be different from the more superficial-lying, free-floating bacteria in the sinuses and that this may impact on the microbiome results obtained. This study investigates whether there is a significant difference in the microbiota of a sinonasal mucosal tissue sample versus a swab sample.
METHODS: Cross-sectional study with paired design. Mucosal biopsy and swab samples were obtained intra-operatively from the ethmoid sinuses of 6 patients with CRS. Extracted DNA was sequenced on a Roche-454 sequencer using 16S-rRNA gene targeted primers. Data were analyzed using QIIME 1.8 software package.
RESULTS: At a maximum subsampling depth of 1,100 reads, the mean observed species richness was 33.3 species (30.6 for swab, versus 36 for mucosa; p > 0.05). There was no significant difference in phylogenetic and non-phylogenetic alpha diversity metrics (Faith's PD_Whole_Tree and Shannon's index) between the two sampling methods (p > 0.05). The type of sample also had no significant effect on phylogenetic and non-phylogenetic beta diversity metrics (Unifrac and Bray-Curtis; p > 0.05).
CONCLUSION: We observed no significant difference between the microbiota of mucosal tissue and swab samples. This suggests that less invasive swab samples are representative of the sinonasal mucosa microbiome and can be used for future sinonasal microbiome studies.
J Laryngol Otol. 2015 Jul;129 Suppl 3:S35-40. doi: 10.1017/S0022215115000778. Epub 2015 Apr 8.
OBJECTIVES: To analyse the radiological features of the bony nasolacrimal duct before and after functional endoscopic sinus surgery, and document the incidence of surgically induced dehiscence.
METHODS: A retrospective case series analysis was conducted of 63 consecutive patients who underwent uncinectomy as a part of 118 functional endoscopic sinus surgical procedures. All patients underwent pre- and post-operative computed tomography scans. Axial computed tomography images at the level of maxillary sinus were evaluated for the presence of bony nasolacrimal duct dehiscence, osteitis and completeness of uncinectomy.
RESULTS: The rate of nasolacrimal duct dehiscence prior to surgery was 6.8 per cent (8 out of 118 cases). Nasolacrimal duct dehiscence as a consequence of surgery was observed in 3.3 per cent of cases (4 out of 118), with a further 4.2 per cent (5 out of 118) showing post-operative reactive bony change of the nasolacrimal duct in the absence of dehiscence.
CONCLUSION: The incidence of nasolacrimal duct injury observed was much lower than that previously reported in the literature.
Int Forum Allergy Rhinol. 2015 Apr;5(4):344-52. doi: 10.1002/alr.21457. Epub 2014 Dec 22.
BACKGROUND: The objective of this work was to report success rates as well as potential obstacles in transnasal endoscopic resection of anterior skull base meningiomas.
METHODS: The study design was a case series with chart review at tertiary referral centers in South Australia and New Zealand. The patients were 37 consecutive patients who underwent endoscopic resection of skull-base meningiomas between 2004 and 2013. Review of patient charts and operative details were performed. Outcomes including complications are reported.
RESULTS: Eighty-four percent of patients were women. There were 28 primary and 9 revision cases. Tumor locations were as follows: 14 olfactory groove/subfrontal; 12 planum/jugum sphenoidale; 7 tuberculum sellae; 3 clinoidal; and 1 clival. Vision change was the most common presenting symptom. Mean tumor volume was 33.68 cm(3) , mean diameter was 2.78 cm. Average operating times decreased with an initial learning curve and then plateaued. Primary tumors larger than 60 cm(3) took an average of 10 hours to resect. Gross total removal was achieved in 29 patients. There were no perioperative deaths. Two deaths occurred within 1 year of surgery. Postoperative cerebrospinal fluid (CSF) leaks occurred in 13 patients. Seventy-five percent of patients presenting with visual loss reported visual improvement. Of the 29 patients considered to have had complete resection at surgery, one was found to have residual disease on a postoperative magnetic resonance imaging (MRI) and another one later developed radiological evidence of recurrence.
CONCLUSION: Using a 2-team approach, meningiomas of the skull base were successfully removed via an intranasal endoscopic technique. Although complete resection is typically possible even with large tumors, the lengthy resection required time for tumors larger than 60 cm(3) (diameter ≥4 cm) may obviate some of the advantages of this approach. The rate of postoperative CSF leak decreases when a synthetic dural substitute is added but does not approach zero.
Clin Ophthalmol. 2014 Dec 9;8:2491-9. doi: 10.2147/OPTH.S73998. eCollection 2014.
AIM: This study aims to provide a systematic protocol for the evaluation of a dacryocystorhinostomy (DCR) ostium and to propose a scoring system to standardize the assessment.
METHODS: Retrospective evaluation of 125 consecutive lacrimal ostia post-DCR was performed. Medical records were screened, and photographs and videos were assessed to note the details of various ostial parameters. The major time points in evaluation were 4 weeks, 6 weeks, 3 months, and 6 months post-DCR. The ostia were defined and parameters like shape, size, location, and evolution of ostium were noted. Evaluation parameters were defined for internal common opening (ICO), ostium stents, and ostium granulomas. Ostium cicatrix and synechiae were graded based on their significance. Surgical success rates were computed and ostium characteristics in failed cases were studied.
RESULTS: A total of 125 ostia were evaluated on the aforementioned ostium parameters. Because five ostia showed a complete cicatricial closure with no recognizable features, the remaining 120 ostia were studied. The ostium location was anterior to the axilla of middle turbinate in 85.8% (103/120) of the cases. Moreover, 76.6% (92/120) of the ostia were circular to oval in shape, with a shallow base. The ostium size was >8×5 mm in 78.3% (94/120) of the cases. The ICO was found to be located in the central or paracentral basal area in 75.8% (91/120). The anatomical and functional success rates achieved were 96% and 93.6%, respectively. All the five cases with anatomical failures showed a complete cicatrization and the ICO movements were poor in all the three cases of functional failure.
CONCLUSION: The article attempts to standardize the postoperative evaluation of a DCR ostium and provides a systematic protocol and scoring system for possible use by surgeons and researchers alike.
Am J Rhinol Allergy. 2014 Nov-Dec;28(6):514-6. doi: 10.2500/ajra.2014.28.4096.
BACKGROUND: This study compares the anatomic and functional outcomes of primary powered endoscopic dacryocystorhinostomy (DCR) in surgeons of differing levels of experience.
METHODS: A retrospective interventional study was performed of all consecutive powered endoscopic DCRs performed at a tertiary institution over a period of 10 years from 2002 to 2012. All patients completed a minimum of 3 months follow-up after stent removal. Patient records were reviewed for demographic data, clinical and surgical profiles, adjunctive procedures, complications, and success rates at last follow-up. The level of surgeon's experience performing the DCR was also documented. Anatomic success was defined as patent ostium on irrigation and functional success as free flow of dye into ostium on functional endoscopic dye test and resolution of epiphora.
RESULTS: Among the 160 DCRs performed by the consultant, all except four underwent intubation; 54.4% (68/125) of these patients required adjunctive procedures. There were no major complications in this group and at a long-term mean follow-up of 14.2 months, the anatomic and functional success rates were 98.1 and 95.6%, respectively. Among the 100 DCRs performed by the fellows, all underwent intubation and 40.8% (29/71) of the patients required adjunctive procedures. The complications include three cases of ostium granulomas and two patients each with postoperative bleeding, stent prolapse, and turbinoseptal synechiae. At the mean follow-up of 10.9 months, the final anatomic success was achieved in 95% of the cases and functional success in 89% of the cases.
CONCLUSION: Powered endoscopic dacryocystorhinostomy is an effective procedure and offers excellent results in the hands of experienced surgeons. A good transfer of knowledge and skills along with supervision when required ensures a good surgical success rate, even when the training fellows operate.
Clin Exp Ophthalmol. 2015 Jul;43(5):405-8. doi: 10.1111/ceo.12483. Epub 2015 Jan 15.
BACKGROUND: This study aims to assess the effects and outcomes of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA) in patients who have undergone endoscopic dacryocystorhinostomy (DCR).
DESIGN: Retrospective series in a university setting.
PARTICIPANTS: A total of 205 consecutive patients were included in this study.
METHODS: A 10-year retrospective review was performed of 205 consecutive patients who had undergone powered endoscopic DCR for nasolacrimal duct obstruction. Patient notes were reviewed for demographic, clinical and surgical information. In addition, all patients were contacted and asked to complete a standardized telephone survey relating to OSA, CPAP use and associated symptoms.
MAIN OUTCOME MEASURE: Effects of CPAP following DCR.
RESULTS: Ten of the 205 patients undergoing DCR were identified to use CPAP for obstructive sleep apnoea. Eight patients were initiated on a nasal device, while two used a full-face mask. The mean CPAP pressures were 8 cm H20 (range: 6-10 cm H20). Eighty percent (8/10) of patients complained of symptoms from the use of their CPAP following DCR. The most commonly described symptom was that of air regurgitation in 70% of patients followed by ophthalmic symptoms in 60% (6/10). 50% (5/10) of patients discontinued their CPAP as a consequence of their symptoms with 20% (2/10) discontinuing because of intolerable ophthalmic symptoms.
CONCLUSION: Symptoms from CPAP use post-endoscopic DCR are a common occurrence and may contribute to poor compliance with CPAP therapy. Detailed preoperative counseling with regards to CPAP use and its effects should be mandatory in known or at risk OSA patients undergoing DCR.
Ophthalmic Plast Reconstr Surg. 2015 Sep-Oct;31(5):396-400. doi: 10.1097/IOP.0000000000000361.
PURPOSE: Biofilms are now recognized as potential factors in the pathogenesis of chronic inflammatory and infective diseases. The aim of this study was to examine the presence of biofilms and quantify their biomass on silastic nasolacrimal duct stents inserted after dacryocystorhinostomy (DCR).
METHODS: A prospective study was performed on a series of patients undergoing DCR with O'Donoghue stent insertion. After removal, the stents were subjected to biofilm analysis using standard protocols of confocal laser scanning microscopy (CLSM) and scanning electron microscopy. These stents were compared against negative controls and positive in vitro ones established using Staphylococcus aureus strain ATCC 25923. Biofilm quantification was performed using the COMSTAT2 software and the total biofilm biomass was calculated.
RESULTS: A total of nine consecutive patient samples were included in this prospective study. None of the patients had any evidence of postoperative infection. All the stents demonstrated evidence of biofilm formation using both imaging modalities. The presence of various different sized organisms within a common exopolysaccharide matrix on CLSM suggested the existence of polymicrobial communities. The mean biomass of patient samples was 0.9385 μm³/μm² (range: 0.3901-1.9511 μm³/μm²).
CONCLUSIONS: This is the first study to report the quantification of biomass on lacrimal stents. The presence of biofilms on lacrimal stents after DCR is a common finding but this need not necessarily translate to postoperative clinical infection.
Int Forum Allergy Rhinol. 2014 Dec;4(12):986-94. doi: 10.1002/alr.21373. Epub 2014 Nov 14.
BACKGROUND: Olfactory dysfunction is common among patients with chronic rhinosinusitis and has a negative impact upon quality of life. Olfactory dysfunction can be both subjective and objective and appears to be more predominant in patients with concomitant nasal polyposis. The efficacy of medical interventions on olfaction among patients with CRS with nasal polyposis (CRSwNP) is not well known. Our aim was to perform a systematic review with meta-analysis of the efficacy of medical therapies on objective and subjective hyposmia among patients with CRSwNP.
METHODS: Olfaction specific outcomes from randomized controlled trials evaluating medical interventions on patients with CRSwNP were evaluated. Interventions included corticosteroids, antibacterials, antifungals, diuretics, herbals and anti-immunoglobulin E (IgE) medications.
RESULTS: A total of 28 randomized control trials evaluation olfaction in CRSwNP was identified and systematically reviewed. Sufficient data for meta-analysis was retrieved for 5 trials. In the meta-analysis, oral steroids showed significant improvement in subjective olfaction scores compared to placebo (standardized mean difference [SMD] -2.22; 95% confidence interval [CI], -3.94 to -0.49). Oral steroids also showed significant improvement in objective olfaction scores compared to placebo (SMD 0.65; 95% CI, 0.28 to 1.01). In the systematic review, both topical steroids and combined topical and oral steroid groups showed overall improvement in subjective olfaction outcomes. Antibacterials, antifungals, herbals, and anti-IgE medications had no impact on overall olfaction scores.
CONCLUSION: The results of this meta-analysis demonstrated that oral and topical steroids significantly improve olfaction in patients suffering from CRSwNP.
Int Forum Allergy Rhinol. 2015 Jan;5(1):60-5. doi: 10.1002/alr.21407. Epub 2014 Oct 13.
BACKGROUND: Endoscopic maxillary mega-antrostomy (EMMA) is a revision surgical procedure for recalcitrant maxillary sinusitis in which medical therapy and endoscopic antrostomy have been unsuccessful. In 2008 our group published favorable outcomes of EMMA in 28 patients with relatively short follow-up and nonvalidated outcome measures. This study reports an update of long-term outcomes of this same cohort, as well as outcomes of an interval cohort of 94 patients using validated outcome measures.
METHODS: Retrospective review was performed for 122 patients (163 sides) who underwent EMMA between 2005 and 2013. For the original 2008 cohort, the original questionnaire from 2008 was readministered by telephone interview. For the interval cohort, preoperative and postoperative SNOT-22 symptom scores and modified Lund-Kennedy endoscopic scores were compared.
RESULTS: The original 2008 cohort of 28 patients, now with a mean follow-up period of 6.9 years, demonstrated sustained improvement of symptoms. The outcomes were statistically comparable to the 2008 study, with 72.4% reporting complete or significant improvement, 27.6% reporting partial improvement, and 0% reporting worsening.
Int Forum Allergy Rhinol. 2014 Dec;4(12):953-60. doi: 10.1002/alr.21423. Epub 2014 Oct 1.
BACKGROUND: Staphylococcus aureus infection is known to play a role in recalcitrant chronic rhinosinusitis (CRS). However, it is unknown if recurrent S. aureus infections are caused by the same strain or are due to independent acquisitions of different strains.
METHODS: Samples were collected from patients with CRS from July 2011 to August 2012. S. aureus was isolated from mucosal swabs and tissue specimens from patients who underwent surgery during the study period, or from swabs of areas of purulence taken in the postoperative period under endoscopic guidance. Pulsed-field gel electrophoresis was used to characterize S. aureus isolates.
RESULTS: Thirty-four patients were included in the study; 79% showed persistence of the same S. aureus strain in their paranasal sinuses (p = 0.001; H1 ≠ 50%). Furthermore, a significantly high frequency of patients with known biofilm status were positive for S. aureus biofilm (p = 0.002; H1 ≠ 50%). When patients were stratified according to disease evolution postsurgery, certain strains appeared to be more commonly associated with symptom persistence.
CONCLUSION: The same S. aureus strain appears to persist in the paranasal sinuses of CRS patients despite multiple courses of culture-directed antibiotics. This suggests that conventional antimicrobial therapies in patients with CRS may not eliminate the organism. This may be partly explained by the formation of biofilms in the paranasal sinus region.
Am J Rhinol Allergy. 2014 Sep-Oct;28(5):438-42. doi: 10.2500/ajra.2014.28.4073.
BACKGROUND: The impact of intraoperative hydrodebrider sinus irrigation (HSI) during endoscopic sinus surgery (ESS) on postoperative inflammation, endoscopy, and patient-reported outcomes has not been studied.
METHODS: A clinical trial of 12 patients with symmetric chronic rhinosinusitis were prospectively randomized to HSI on one side after undergoing bilateral ESS. The contralateral side was not treated with any irrigation and served as an internal control. Preoperative computed tomography, endoscopic, 22-item Sino-Nasal Outcome Test (SNOT-22), and symptom visual analog scale (VAS) scores for each side were obtained. At 1 and 3 months postsurgery, endoscopy, SNOT-22, and sinus VAS were recorded. Sinonasal mucus levels of interleukin (IL)-6, IL-10, IL-17a, and tumor necrosis factor (TNF) alpha were measured at the time of surgery, 1 and 3 months, postoperatively, from each side.
RESULTS: VAS scores improved on both sides (p < 0.05) and SNOT-22 improved at all postoperative time points (p < 0.05). Endoscopic scores of HSI-treated sides did not improve compared with baseline. HSI had no additional significant impact on postoperative VAS at any time point. HSI significantly decreased IL-17a levels when compared with the control side at 1 month (p = 0.034) and 3 months (p = 0.031). No significant change was seen in TNF-alpha, IL-6, or IL-10 on either side at any time point.
CONCLUSION: Intraoperative HSI at the time of ESS failed to establish any improvement in postoperative endoscopy or most local cytokine levels after ESS.
Int Forum Allergy Rhinol. 2014 Dec;4(12):1016-9. doi: 10.1002/alr.21398. Epub 2014 Aug 31.
BACKGROUND: Long-term outcomes of revision dacryocystorhinostomy are less known. The aim of this study was to assess the long-term outcomes of revision powered endoscopic dacryocystorhinostomy (DCR).
METHODS: Retrospective review of all consecutive revision powered endoscopic DCRs performed over a period of 10 years from 2003 to 2012 were included. All patients completed a minimum of 12 months follow-up following stent removal. Patient records were reviewed for demographic data, type of past surgery, causes of failure, clinical and surgical profiles, adjunctive procedures, complications, and success rates at last follow-up.
RESULTS: Twenty-three revision powered endoscopic DCRs were performed on 18 patients who had failed primary DCR. The mean age at surgery was 61 years (range, 28-84 years). All patients presented with epiphora. Nearly 67% (66.7%; 12/18) were failed endoscopic DCRs and 33.3% (6/18) were failed external DCRs. The most common cause of failure was from cicatricial closure of ostium in 55.5% (10/18) of the cases. Over 44% (44.4%; 8/18) of patients underwent adjunctive endonasal procedures at the time of revision endoscopic DCR. The mean follow-up was 26.4 months (range, 12-66 months). A complication of ostium granuloma in 1 patient was noted, which was successfully managed. At the last follow-up, anatomical success was achieved in 91.3% of the cases and functional success in 86.9%.
CONCLUSION: Powered endoscopic DCR is a suitable option for revising failed DCRs and offers good long-term results. Meticulous evaluation to identify causative factors of failure and addressing them is crucial for successful outcomes.
Ophthalmic Plast Reconstr Surg. 2015 May-Jun;31(3):219-21. doi: 10.1097/IOP.0000000000000261.
PURPOSE: To report a decade long experience with powered endoscopic dacryocystorhinostomy (DCR).
METHODS: A retrospective review of all consecutive patients undergoing powered endoscopic DCR was performed at this institution over a period of 11 years from 2002 to 2013. All patients completed a minimum of 3 months follow up following stent removal. Patient records were reviewed for demographic data, clinical and surgical profiles, adjunctive procedures, complications, and success rates at the last follow up. Anatomical success was defined as patent ostium on irrigation and functional success as free flow of dye into ostium on functional endoscopic dye test and resolution of epiphora.
RESULTS: Two hundred eighty-three powered endoscopic DCRs were performed on 214 patients. The mean age at surgery was 59.5 years (range, 3-95 years). All patients presented with epiphora. A total of 91.6% patients (196/214) had a primary DCR and 8.4% (18/214) had a revision DCR. In all, 50.4% patients (108/214) underwent adjunctive endonasal procedures. The mean follow up was 17.1 months (range, 3-103 months). At the last follow up, the final anatomical success was achieved in 96.9% cases of primary DCRs and 91.3% cases of revision DCRs. Functional success was achieved in 93% cases of primary DCRs and 86.9% cases of revision DCRs.
CONCLUSIONS: Powered endoscopic DCR is a safe procedure and offers excellent results both in primary and revision DCRs. The threshold to perform adjunctive endonasal procedures should be very low when indicated.
Otolaryngol Head Neck Surg. 2014 Oct;151(4):575-81. doi: 10.1177/0194599814545750. Epub 2014 Aug 12.
OBJECTIVE: This study aimed to assess sinonasal outcomes in patients with aspirin exacerbated respiratory disease (AERD) undergoing aspirin desensitization following endoscopic sinus surgery (ESS).
STUDY DESIGN: Case series with chart review.
SETTING: University hospital.
SUBJECTS AND METHODS: A retrospective review of sinonasal outcomes was conducted for 30 AERD patients undergoing aspirin desensitization and maintenance therapy following ESS. Sinonasal outcomes were prospectively assessed by the Sinonasal Outcomes Test-22 (SNOT-22) and endoscopic polyp grading system. Data were collected preoperatively, 1 and 4 weeks postsurgery (before desensitization), and 1, 6, 12, 18, 24, and 30 months after aspirin desensitization.
RESULTS: Twenty-eight of 30 patients (93.3%) successfully completed aspirin desensitization, whereas 2 of 30 (6.7%) were unable to complete desensitization due to respiratory intolerance. Of the 21 patients who successfully completed a minimum of 24 weeks of follow-up, 20 (95.2%) patients demonstrated sustained endoscopic and symptomatic improvement for a median follow-up period of 33 months. After surgical treatment but before desensitization, patients experienced significant reductions in SNOT-22 and polyp grade scores. In the first 6 months after aspirin desensitization, patients experienced further significant reductions in SNOT-22 scores, whereas polyp grade remained stable. The improvements in symptom endoscopic scores were preserved throughout the follow-up period after desensitization. No patients required additional sinus surgery. One patient had to discontinue aspirin therapy due to gastrointestinal side effects. No other adverse reactions to aspirin were noted.
CONCLUSION: Aspirin desensitization following ESS appears to be a well-tolerated and effective adjunctive therapy for long-term control of nasal polyposis in patients with AERD.
Laryngoscope. 2015 Jan;125(1):80-5. doi: 10.1002/lary.24863. Epub 2014 Aug 11.
OBJECTIVES/HYPOTHESIS: To analyze complications associated with nasoseptal flap elevation and reconstruction in endoscopic skull base surgery.
STUDY DESIGN: Case series.
METHODS: Retrospective chart review of all patients who underwent nasoseptal flap procedure in our institution between 2008 and 2013.
RESULTS: A total of 121 patients were identified with a mean follow-up time of 10.4 months. Complications associated with this procedure occurred in 33 patients (27%). The majority of complications were related to the septal donor site and included septal perforation, cartilage necrosis, and prolonged crusting. Other complications included intraoperative injury to the flap pedicle (n = 4) or recurrent/persistent cerebrospinal fluid leak occurring in the early postoperative period (n = 7). Long-term quality-of-life data assessed via Sinonasal Outcome Test-22 questionnaires did not reveal notable differences when compared to preoperative scores.
CONCLUSION: The complication rate associated with nasoseptal flap elevation and inset is higher than previously described. The majority of complications became manifest beyond the immediate postoperative period and were associated with the septal donor site, including septal perforation, prolonged crusting, and cartilage necrosis. We hypothesize that donor site morbidity may be related to compromise of the contralateral septal vascular supply during the procedure. The range and frequency of complications of nasal septal flap surgery should be considered in counseling patients who may receive a nasoseptal flap for skull base reconstruction.
Br J Ophthalmol. 2014 Dec;98(12):1678-80. doi: 10.1136/bjophthalmol-2014-305510. Epub 2014 Jul 4.
AIM: To assess the long-term anatomical and functional outcomes of primary powered endoscopic dacryocystorhinostomy (DCR).
METHODS: Retrospective review of all primary powered endoscopic DCR's performed over a 10-year period from 2003 to 2012. A minimum of 12 months follow-up after stent removal was required for inclusion into this study. Patient records were reviewed for demographic data, clinical and surgical profiles, adjunctive procedures, complications and success rates at last follow-up. Anatomical success was defined as a patent ostium on irrigation, and functional success as free flow of dye into ostium, and resolution of epiphora.
RESULTS: Ninety powered endoscopic DCRs were performed on 69 patients. The mean age at surgery was 58.7 years (range 4-91 years). All patients presented with epiphora. 50.7% (35/69) patients underwent adjunctive endonasal procedures. The mean follow up was 21.8 months (range: 12-103 months). No intraoperative complications were noted. Postoperative complications noted included postoperative bleeding, ostium granuloma and membrane over internal common opening in one patient each. At last follow-up, the final anatomical success was achieved in 97.7% and functional success in 95.5% of the cases.
CONCLUSIONS: Powered endoscopic DCR is a safe procedure and offers excellent long-term results. Adjunctive endonasal procedures should be performed where indicated.
Clin Exp Ophthalmol. 2015 Mar;43(2):152-5. doi: 10.1111/ceo.12383. Epub 2014 Aug 12.
BACKGROUND: This study aims to assess the shrinkage of dacryocystorhinostomy (DCR) ostium beyond 4 weeks.
DESIGN: Prospective series in a University setting.
PARTICIPANTS: Sixty consecutive patients.
METHODS: Prospectively collected data of 60 consecutive powered endoscopic DCRs performed in 57 patients over a period of 10 years from 2002 to 2011. All patients had regular follow-up of 2 years post-surgery. The ostium size at 4 weeks, 6 months, 1 year and 2 years were evaluated. Analysis of variance was used to compare the differences.
MAIN OUTCOME MEASURE: Changes in ostium measurements.
RESULTS: The ostium measured 11.25 mm (standard deviation [SD] = 1.7; 95% confidence intervals [CI] = 10.80-11.69) × 7.07 (SD = 1.4; 95% CI = 6.71-7.42) at 4 weeks. It measured 10.48 mm (SD = 1.6; 95% CI = 10.06-10.90) × 6.65 mm (SD = 1.2; 95% CI = 6.34-6.95) at 6 months, 10.22 mm (SD = 1.5; 95% CI = 9.81-10.61) × 6.52 mm (SD = 1.2; 95% CI = 6.20-6.80) at 1 year and 10.15 mm (SD = 1.5; 95% CI = 9.76-10.53) × 6.45 mm (SD = 1.2; 95% CI = 6.14-6.75). There was no statistically significant decrease in either the ostium size or the area up to 2 years following surgery.
CONCLUSION: The ostium achieved using the powered endoscopic DCR technique remains stable in size from 4 weeks to 2 years post-surgery. This likely reflects the advantages of this technique which facilitates healing by primary intention.
Ophthalmic Plast Reconstr Surg. 2014 Jul-Aug;30(4):346-51. doi: 10.1097/IOP.0000000000000206.
PURPOSE: To evaluate the safety and efficacy of a new technique of medial wall cruciate marsupialization of large intranasal cysts associated with dacryocele and to evaluate the outcomes.
METHODS: A prospective, interventional consecutive case series of 7 patients with large intranasal cysts were included in this study. All patients underwent endoscopic marsupialization by a single surgeon (MJA) using a new technique involving a medial wall cruciate incision. Patients were followed up for a minimum of 6 months and analyzed for the resolution of dacryocele and intranasal cysts and anatomical and functional success.
RESULTS: The mean age at presentation was 5.9 weeks with a female preponderance (71.4%). All patients presented with a subcutaneous swelling in lacrimal sac region. Acute dacryocystitis was noted in 42.8% (3/7). Associated lacrimal anomalies were noted in 28.5% (2/7), and associated respiratory distress was noted in 57.1% (4/7) of the patients. At a mean follow up of 10.8 months, anatomical patency and resolution of intranasal cyst were achieved in all cases, and functional success was noted in all except 1 patient.
CONCLUSIONS: Endoscopic evaluation of all dacryoceles is recommended. Medial wall cruciate marsupialization is a safe and effective modality in the management of large intranasal cysts. Early diagnosis and appropriate quick referral are likely to prevent acute dacryocystitis, progression of dacryocele, and may aid in better outcomes.
Am J Rhinol Allergy. 2014 Jul-Aug;28(4):308-11. doi: 10.2500/ajra.2014.28.4066. Epub 2014 May 22.
BACKGROUND: This study was designed to determine if the addition of large-volume, low-positive pressure nasal irrigations delivered with isotonic sodium chloride (hereinafter "saline") added to intranasal corticosteroid therapy improves quality of life and objective measures of nasal breathing in patients with allergic rhinitis when compared with intranasal corticosteroid alone.
METHODS: A prospective, unblinded, single-arm pilot study was performed of patients with allergic rhinitis already on intranasal corticosteroid pharmacotherapy. Patients added large-volume low-pressure saline irrigation twice daily for 8 weeks to their ongoing regiment of nasal corticosteroid. Mini-Rhinoconjunctivitis Quality of life Questionnaire (mRQLQ) assessment and nasal peak inspiratory flow (NPIF) were performed at baseline and at 4 and 8 weeks.
RESULTS: A total of 40 patients were enrolled. Twice-daily nasal irrigation with isotonic saline significantly (p < 0.001) reduced mRQLQ scores, from 36.7 ± 20.48 (baseline) to 14.9 ± 11.03 (4 weeks) to 10.10 ± 10.65 (8 weeks). No significant changes were seen in NPIF, pattern use of nasal steroid use, or adverse events.
CONCLUSION: Large-volume, low-positive pressure nasal irrigation with isotonic saline is an effective adjunctive therapy to improve quality of life in patients with allergic rhinitis already on intranasal corticosteroid therapy. This study was a part of the clinical trial NCT01030146 registered at clinicaltrials.gov.
Int Forum Allergy Rhinol. 2014 Aug;4(8):684-8. doi: 10.1002/alr.21345. Epub 2014 May 20.
BACKGROUND: Detailed knowledge of the surgical anatomic landmarks of the lateral nasal wall is important for safe and successful endoscopic sinonasal surgery. We sought to determine the relationship of major landmarks to the nasolacrimal duct (NLD).
METHODS: Twenty mid-sagittal head sections of 10 fresh frozen cadavers were studied after removal of the nasal septum. The insertion of the alar cartilage into the maxilla was taken as a fixed point and all measurements were performed in a defined axial plane at the level of the maxillary sinus natural ostium. Two surgeons independently recorded each measurement 3 times with an average of the readings used for statistical analysis.
RESULTS: The overall agreement index was excellent (r = 0.84) between the observers. At the level of maxillary ostium, the mean distance from the alar rim to the NLD was 43.05 ± 4.76 mm on the right and 41.25 ± 4.56 mm on the left. The most anterior projection of the middle turbinate head was noted to be anterior to the NLD in 70% of specimens. In positional relationship, the maxillary line was posterior to the NLD in 55%, whereas the bulla ethmoidalis and the free edge of uncinate process were uniformly posterior to the NLD in all the specimens.
CONCLUSION: This study provides useful anatomic and positional relationships between the NLD and major lateral wall landmarks. Although the maxillary line and the head of the middle turbinate are often considered useful guides to the position of the ipsilateral NLD, their spatial relationship to the NLD is not consistent. These landmarks, therefore, cannot be solely relied upon during surgery to avoid injury to the NLD.
Am J Rhinol Allergy. 2014 Jan-Feb;28(1):e73-9. doi: 10.2500/ajra.2014.28.4002.
BACKGROUND: This study was designed to determine if differences in overall skull base thickness exist in patients with spontaneous cerebrospinal fluid (SCSF) leaks and to compare our institution's 10-year experience with the endoscopic repair of these leaks to the existing literature. A retrospective cohort study was performed in a tertiary rhinologic practice.
METHODS: A retrospective study by two blinded independent reviewers compared the skull base thickness on computerized tomography (CT) imaging in our SCSF leak patients to nonleaking controls and patients with traumatic CSF leaks. Surgical outcomes were compared with a pooled analysis of the published literature.
RESULTS: SCSF leaks were seen most commonly in obese, middle-aged women of African American descent. SCSF leak patients were shown to have thinner skull bases in the region of the ethmoid roof, lateral lamella, and anterior face of the sella (p < 0.05) compared with patients with traumatic leaks and nonleaking controls. No racial difference in skull base thickness was observed when patients were matched according to leak type. The success rate of primary endoscopic intervention in our patients was high at 94% and comparable with the published literature.
CONCLUSION: Differences in skull base thickness exist in SCSF patients, but whether this predisposes to such leaks or is a consequence of the underlying pathophysiology remains unknown. The endoscopic endonasal approach provides a highly effective means of repairing such leaks with success rates comparable with the endoscopic repair of other leak types. Adjuvant measures including weight reduction, lumbar drain, and acetazolamide use may increase success rates and should be considered in their management.
Laryngoscope. 2014 Oct;124(10):2216-23. doi: 10.1002/lary.24654. Epub 2014 Apr 2.
OBJECTIVES/HYPOTHESIS: To compare three existing endoscopic scoring systems and a newly proposed modified scoring system for the assessment of patients with chronic rhinosinusitis (CRS).
STUDY DESIGN: Blinded, prospective cohort study.
METHODS: CRS patients completed two patient-reported outcome measures (PROMs)-the visual analogue scale (VAS) symptom score and the Sino-Nasal Outcome Test-22 (SNOT-22)-and then underwent a standardized, recorded sinonasal endoscopy. Videos were scored by three blinded rhinologists using three scoring systems: the Lund-Kennedy (LK) endoscopic score; the Discharge, Inflammation, Polyp (DIP) score; and the Perioperative Sinonasal Endoscopic score. The videos were further scored using a modified Lund-Kennedy (MLK) endoscopic scoring system, which retains the LK subscores of polyps, edema, and discharge but eliminates the scoring of scarring and crusting. The systems were compared for test-retest and inter-rater reliability as well as for their correlation with PROMs.
RESULTS: One hundred two CRS patients were enrolled. The MLK system showed the highest inter-rater and test-retest reliability of all scoring systems. All systems except for the DIP correlated with total VAS scores. The MLK was the only system that correlated with the symptom subscore of the SNOT-22 in both unoperated and postoperative patients.
CONCLUSIONS: Modification of the LK system by excluding the subscores of scarring and crusting improves its reliability and its correlation with PROMs. In addition, the MLK system retains the familiarity of the widely used LK system and is applicable to any patient irrespective of surgical status. The MLK system may be a more suitable and reliable endoscopic scoring system for clinical practice and outcomes research.
JAMA Otolaryngol Head Neck Surg. 2014 Mar;140(3):253-8. doi: 10.1001/jamaoto.2013.6335.
IMPORTANCE: Bilateral anterior nasal packing is used after septoplasty with the goals of decreasing the risk of postoperative bleeding and adhesions. However, multiple studies caution against the use of nasal packing because of the risk of cardiopulmonary complications.
OBJECTIVE: To evaluate the cardiopulmonary risks associated with bilateral anterior nasal packing after septoplasty.
EVIDENCE REVIEW: A literature review was conducted by 2 independent reviewers using EMBASE, Ovid, Medline, PubMed, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and reference list review from January 1966 to September 2012 to identify studies assessing nasal packing after septoplasty. The studies were reviewed and assigned an Oxford level of evidence grade, Detsky score, and Methodological Index for Nonrandomized Studies (MINORS) score. Data were extracted for arterial blood gases, oxygen desaturations, oxygen saturations, and adverse outcomes. Pooled estimates for randomized studies were performed when possible.
FINDINGS: Fourteen studies conducted between 1973 and 2011 were included: 2 randomized clinical trials (RCTs) with a total of 119 patients and 12 prospective observational studies with a total of 356 patients. Nine studies showed a significant change within 1 of the cardiopulmonary parameters investigated. However, there was no consistency in changes across both observational and randomized studies. Furthermore, pooled estimates for cardiopulmonary parameters were all nonsignificant: standard mean differences of the pooled results of the RCTs were 0.05 (95% CI, -0.31 to 0.41) for arterial pH, 0.08 (95% CI, -0.30 to 0.46) for Paco2, and -0.32 (95% CI, -1.28 to 0.63) for Pao2. There were no major cardiopulmonary complications after nasal packing.
CONCLUSIONS AND RELEVANCE: Bilateral anterior nasal packing does not seem to cause adverse cardiopulmonary changes after septoplasty.
Laryngoscope. 2013 Dec;123(12):E72-8. doi: 10.1002/lary.24305. Epub 2013 Aug 6.
OBJECTIVES/HYPOTHESIS: Compare cytokine levels in sinus tissue to sinus secretions from controls and chronic rhinosinusitis patients.
STUDY DESIGN: In vitro.
METHODS: Polyurethane foam sponges were placed into middle meati of patients with chronic rhinosinusitis without nasal polyps (CRSsNP), with polyps (CRSwNP), and controls. Sinus biopsies were then taken from the same location. Protein levels of tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ), and interleukins (IL) 2, 4, 6, 8, 10, and 17A were measured via cytometric bead assay for each sample. Protein values from sinus tissue and secretions were compared with Pearson's correlation between samples as well as one-way ANOVA with posthoc t test between groups.
RESULTS: Samples from 43 patients in total were examined. Mucus was measured from 10 controls, 11 CRSsNP and 10 CRSwNP, and sinus tissue was measured from 10 controls, 15 CRSsNP and 10 CRSwNP. IL-8 and IFN-γ levels were outside of the detectable range of the assay. Levels of secreted IL-2, 4, 6, 10, and 17A correlated with tissue levels (P < 0.05 for all, r > 0.49) while TNF-α did not (P = 0.71). CRSsNP had elevated mucus levels of IL-2, 4, 6, 10, and 17A compared to controls. CRSwNP had elevated mucus levels of IL-4, 6, 10, 17A, and TNF-α compared to controls.
CONCLUSIONS: Cytokine levels in sinus secretions correlate with levels in sinus tissue and are elevated in CRS versus control based on Th1/Th2 skewing.
Int Forum Allergy Rhinol. 2013 Aug;3(8):621-9. doi: 10.1002/alr.21173. Epub 2013 May 2.
BACKGROUND: Recent research suggest that B and plasma cells may play an important role in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). The purpose of this study was to subcharacterize the B cell response in the sinus mucosa of control and CRS patients.
METHODS: Representative tissue samples and peripheral blood samples were obtained from controls, CRS without nasal polyps (CRSsNP) and CRSwNP. Using single-cell suspension flow cytometry these samples were analyzed for overall and stage-specific B and plasma cell percentages.
RESULTS: Both atopic and nonatopic CRSwNP patients showed an increase in local numbers of naive, active, and memory B cells compared to controls. CRSsNP patients only showed local elevations of naive B cells. Plasma cells were only significantly elevated in the sinus tissue of atopic CRSwNP patients. These local tissue increases did not correlate with increased numbers of circulating B cells.
CONCLUSION: This study provides further evidence of an important role of B cells in CRSwNP patients. The local increase appears to be independent of a systemic response.
Int Forum Allergy Rhinol. 2013 May;3(5):418-24. doi: 10.1002/alr.21110. Epub 2012 Nov 7.
BACKGROUND: Nasal packing is routinely used after septoplasty because it is believed to decrease risk of postoperative bleeding, hematomas, and adhesions. Multiple studies have shown, however, that there are numerous complications associated with nasal packing. The purpose of this work was to perform a meta-analysis on the existing literature to evaluate the role of nasal packing after septoplasty.
METHODS: Two independent reviewers conducted a literature search using EMBASE, OVID, Medline, PubMed, Google scholar, Cochrane Library, and reference list review from 1966 to August 2010 to identify studies assessing nasal packing after septoplasty. All papers were reviewed for study design, results, and were assigned an Oxford level of evidence grade, Detsky score, and Methodological Index for Nonrandomized Studies (MINORS) score.
RESULTS: Sixteen papers were identified that met the inclusion criteria. Eleven papers were randomized control trials, 3 were prospective, and 2 were retrospective studies. Nasal packing did not show benefit in reducing postoperative bleeding, hematomas, septal perforations, adhesions, or residual deviated nasal septum. There was, however, an increase in postoperative infections. Two studies using fibrin products as nasal packing showed a decreased bleeding rate.
CONCLUSION: Nasal packing after septoplasty does not show any postoperative benefits. Fibrin products show a possibility of decreasing postoperative bleeding. Routine use of nasal packing after septoplasty is not warranted. This is the first meta-analysis conducted on this topic.
Laryngoscope. 2012 Oct;122(10):2148-53. doi: 10.1002/lary.23486. Epub 2012 Aug 2.
OBJECTIVES/HYPOTHESIS: Chronic rhinosinusitis (CRS) recalcitrant to surgery is a frustrating clinical entity. Recently, mupirocin sinonasal rinses have been suggested as an efficacious treatment alternative in these patients where Staphylococcus aureus infection is demonstrated. To our knowledge, how best to treat this S aureus reservoir has not been previously evaluated in a double-blinded, randomized, placebo-controlled trial.
STUDY DESIGN: Prospective, double-blinded, placebo-controlled study.
METHODS: Twenty-five S aureus-positive CRS patients with persistent sinonasal infection despite endoscopic sinus surgery received either a 1-month, twice-daily treatment course of mupirocin sinonasal rinses (MUP) or saline rinses (CON). The primary outcome was S aureus-culture negativity at the conclusion of treatment; secondary rhinological outcomes included subjective and objective measures of rhinosinusitis.
RESULTS: Twenty-two patients satisfactorily completed the treatment period. Of CON patients, 0/13 (0.0%) returned an S aureus-negative sinonasal culture at 1 month, compared to 8/9 (88.9%) of MUP patients (P < .01). Improvements in rhinological outcomes observed in MUP patients following treatment were not subsequently evident when these patients were followed up at a delayed assessment 2 to 6 months after completing treatment.
CONCLUSIONS: Mupirocin sinonasal rinses are an effective short-term anti-S aureus treatment in surgically recalcitrant CRS as assessed by microbiological and selected rhinological outcomes, although the latter improvements may not be durable with time.
Laryngoscope. 2012 Oct;122(10):2132-6. doi: 10.1002/lary.23437. Epub 2012 Jul 9.
OBJECTIVES/HYPOTHESIS: To examine the frequency of safe surgical practices specific to endoscopic sinus surgery (ESS) before and after implementation of a checklist at four institutions across North America.
STUDY DESIGN: Prospective, multi-institutional, observational study.
METHODS: Consecutive surgeries were observed at four institutions before (n = 100) and after (n = 100) implementation of the ESS Checklist. A passive observer documented whether 10 specific tasks were performed by the surgical team during the course of each case. The frequency with which each item was performed was tabulated, and differences across institutions were evaluated using the Pearson χ(2) test. Improvement in the frequency of each single item between pre- and postintervention time periods was assessed by the McNemar χ(2) test.
RESULTS: Successful performance of all 10 tasks in the prechecklist period was not observed for any ESS case at any of the four study sites. As might be expected, performance of any individual task was highly variable, ranging from 14% to 95%. After implementation of the ESS Checklist, successful performance of all 10 tasks during an individual surgery increased from 0% to 87% across all institutions, a change that was highly significant (P < .001). Significant increases in the performance of individual tasks was observed for nine of 10 items across all institutions (P ≤ .031 for all).
CONCLUSIONS: Significant heterogeneity exists with regard to performance of specific tasks aimed at minimizing error during ESS. Utilization of the ESS Checklist standardized practice across four institutions and significantly increased the likelihood that individual safety tasks were performed during the course of sinus surgery.
Otolaryngol Head Neck Surg. 2012 Aug;147(2):196-203. doi: 10.1177/0194599812451090. Epub 2012 Jun 15.
OBJECTIVES: To provide an up-to-date review of the literature on the safety and efficacy of the endoscopic technique for cerebrospinal (CSF) leak repairs.
DATA SOURCES: PubMed, Medline/Old Medline, and Cochrane Central databases.
REVIEW METHODS: Using the above outlined data sources, studies involving the endoscopic repair of CSF leaks were reviewed independently by 2 researchers. Studies included met the following criteria: full-text article written in the English language, at least 5 human patients undergoing purely endoscopic surgical repair of a CSF leak, and documented follow-up. Data extracted included leak etiology, presentation and location, the use of imaging, intrathecal fluorescein, and adjunctive measures as well as the success rate of the repair.
RESULTS: Fifty-five studies, involving 1778 fistulae repairs, were included for analysis. Spontaneous leaks were most prevalent, with the ethmoid roof and sphenoid the most common sites involved. The overall success rate of repair was high at 90% for primary and 97% for secondary repairs. A low complication rate of less than 0.03% was reported.
CONCLUSION: The endoscopic repair of CSF fistula is both safe and effective and should be considered the standard of care for most cases. Evidence supporting adjunctive measures such as lumbar drains and antibiotics remains limited despite their common use.
Am J Rhinol Allergy. 2012 May-Jun;26(3):201-3. doi: 10.2500/ajra.2012.26.3747.
BACKGROUND: The use of saline and topical medications in the treatment of chronic rhinosinusitis (CRS) is now common practice among otolaryngologists. Although high-level studies have consistently shown the benefit of saline in symptom improvement of CRS patients, to date, only lower-level evidence exists advocating a benefit of other topical medications.
METHODS: Recently, increased interest has emerged surrounding the devices used to deliver such therapies with mounting evidence consistently showing contamination with pathogenic organisms such as Staphylococcus aureus and Pseudomonas aeruginosa.
RESULTS: In addition, the potential for such contamination to cross-infect sinus cavities and lead to postoperative infections is also of concern.
CONCLUSION: This review examines the current evidence available concerning the issue of contamination and its clinical relevance and offers the otolaryngologist advice on patient education when dispensing such devices.
Int Forum Allergy Rhinol. 2012 Sep-Oct;2(5):357-61. doi: 10.1002/alr.21036. Epub 2012 Mar 23.
BACKGROUND: Sinus surgery remains one of the most commonly performed procedures in the United States, with more than 600,000 patients undergoing sinus operations each year. Advances in our understanding of chronic rhinosinusitis (CRS), as well as the technology used to treat it, has resulted in significant changes in surgical management. The aim of this study was to identify recent changes in the performance and coding of certain endoscopic sinus surgical procedures (ESS) in the hope of generating further discussion and research in this area.
METHODS: The MarketScan Research Database was used to query health insurance claims for all rhinological procedures performed between 2007 and 2009. Current Procedural Terminology (CPT) codes for sinonasal procedures that are endorsed by the American Medical Association were analyzed and compared to general otolaryngological procedures in an attempt to identify trends in the performance and coding of certain ESS procedures.
RESULTS: Compared to general otolaryngological procedures such as adenotonsillectomy, there was a statistically significant increase in the use of CPT codes for all ESS procedures between 2007 and 2009. The most marked interval changes were seen in the use of the CPT codes for procedures previously considered more complex, namely frontal sinusotomy (75%), sphenoidotomy (33%), and maxillary antrostomy with tissue removal (31%).
CONCLUSION: The performance of certain ESS procedures previously considered more complex due to anatomy, access, and proximity to vital structures has increased dramatically in the past few years, whereas increases in basic procedures have mirrored anticipated changes similar to those seen in general otolaryngological procedures.
Curr Allergy Asthma Rep. 2012 Apr;12(2):127-35. doi: 10.1007/s11882-012-0246-7.
Chronic rhinosinusitis (CRS) is a very common condition that remains poorly understood from a pathogenic standpoint. Recent interest has been sparked by a potential role for biofilms in this process, with a significant body of evidence implicating them in inciting sinonasal inflammation. Biofilms are clearly present on the sinus mucosa of CRS patients, and their presence there is associated with severe disease characteristics and surgical recalcitrance. We are beginning to understand the importance of the species within these biofilms, but there may be other as-yet-unidentified factors at play in influencing disease outcomes. Recent exciting research has emerged documenting the immune response to the presence of biofilms-research that will ultimately solidify the nature and extent of the contribution of biofilms in CRS pathogenesis. Future research should focus on evidence-based antibiofilm treatments with reference to efficacy and timing of treatment.
Am J Rhinol Allergy. 2011 Sep-Oct;25(5):323-6. doi: 10.2500/ajra.2011.25.3659.
BACKGROUND: Biofilms in chronic rhinosinusitis (CRS) patients are associated with recalcitrant disease patterns. Citric acid/zwitterionic surfactant (CAZS) has been shown to have significant efficacy at in vitro biofilm eradication. Unique hydrodebrider systems have been shown to have effective antibiofilm efficacy. The aim of this study was to evaluate the efficacy of the CAZS/hydrodebrider treatment on Staphylococcus aureus biofilms in the sheep model of CRS.
METHODS: Forty-two sheep frontal sinuses were inoculated with S. aureus, followed by 7 days of biofilm growth. Sinuses were randomized to one of nine treatment groups: control, hydrodebrider with saline or CAZS (killed on day 0 or day 7 posttreatment), CAZS, or saline flush (killed on day 0 or day 7 posttreatment). Confocal scanning laser microscopy (CSLM) was used to confirm extent of biofilm reduction. Samples of each sinus were taken, assessing cilia morphology using electron microscopy.
RESULTS: A mean of 37.22 ± 9.65% of control (no treatment) CSLM images taken showed biofilms. Both CAZS flush and CAZS/hydrodebrider treatments showed initial improvements in biofilms but biofilm regrowth followed treatment, 14.74 ± 9.58% to 18.91 ± 12.14% and 15.60 ± 13.92% to 24.70 ± 3.66%, respectively (p > 0.05). Saline/hydrodebrider treatments showed a nonsignificant improvement in biofilm treatment, which was maintained, 18.34 ± 11.85% to 12.04 ± 10.28% (p > 0.05). Cilial morphology grade was significantly worse in the CAZS treatment groups (p < 0.05).
CONCLUSION: CAZS solution (with and without a hydrodebrider system) can significantly adversely affect cilia morphology. The hydrodebrider system, when combined with saline, may be a useful treatment adjunct for mucosal biofilms.
Allergy. 2011 Nov;66(11):1449-56. doi: 10.1111/j.1398-9995.2011.02678.x. Epub 2011 Aug 11.
BACKGROUND: The etiopathogenesis of chronic rhinosinusitis (CRS) is currently an area of intense debate. Recently, biofilms have been proposed as a potential environmental trigger in this disease. In particular, Staphylococcus aureus biofilms appear to be a predictor of severe disease recalcitrant to current treatment paradigms. However, direct causal links between biofilms and host immune activation are currently lacking. This study aimed to document both the adaptive immune responses that characterize S. aureus biofilm-associated CRS and the relative contributions of staphylococcal superantigens and S. aureus biofilms in the inflammatory make-up of this disease.
METHODS: A total of 53 disease subjects and 15 controls were recruited. Sinonasal mucosa was collected for the determination of S. aureus and Haemophilus influenzae biofilms and presence of total and superantigen-specific IgE and for the measurement of cytokines that characterize the T-helper pathways.
RESULTS: Staphylococcus aureus biofilms and superantigens are significantly associated in CRS patients, suggesting the biofilm may be a nidus for superantigen-eluting bacteria. The presence of S. aureus biofilms is associated with eosinophilic inflammation, across the spectrum of CRS, on the back of a T-helper(2) skewing of the host's adaptive immune response (elevated Eosinophilic Cationic Protein and IL-5). This can be distinguished from the superantigenic effect resulting in the induction of IgE.
CONCLUSION: This study provides novel evidence of a link between S. aureus biofilms and skewing of the T-cell response toward the T-helper(2) pathway that is independent of superantigen activities. Further research is required to confirm the cause-effect relationship of this association.
Am J Rhinol Allergy. 2010 Sep-Oct;24(5):319-24. doi: 10.2500/ajra.2010.24.3504.
BACKGROUND: Increasingly bacterial biofilms have been implicated in chronic rhinosinusitis (CRS), and conventional treatment methods have failed to completely eradicate biofilms. (1) Terminal sialic acids present on sinus mucosal glycoproteins are targets for bacterial adherence and biofilm formation. (2) A subpopulation of CRS patients is more susceptible to biofilm formation due to aberrant terminal sialic residue distribution patterns of glycoproteins on their mucosa. (3) The higher levels of sialyl transferase (ST)6Gal1 gene expression contribute to the overall aberrant glycosylation patterns on the host mucosa that predispose this patient cohort to developing biofilms. (4) Mucin glycoprotein MUC7 that has known bactericidal activity displays an overall reduced terminal sugar profile in biofilm positive CRS patients.
METHODS: Confocal scanning laser microscopy, glycoarray analysis, real-time polymerase chain reaction of ST6Gal1, neuraminidase assays and multivariate analysis were used to compare production of sialic acid-degrading enzymes in sinus biopsies from biofilm positive and negative CRS patients with mucosa from healthy controls.
RESULTS: Biofilm-positive CRS patients expressed aberrant glycoprotein patterns with terminal sialics of between 70 and 90 kD (stress value = 0.1414). The ST6Gal1 gene was upregulated, and bacteria isolated from these patients exhibit significantly higher neuraminidase activity (p = 0.0343). We detected a significant lack in the overall expression of terminal sugar residues of MUC7 (stress value = 0.088).
CONCLUSIONS: We observed a strong positive correlation between the aberrant terminal sugar patterns in this sub group of CRS patients with biofilms. The innate immunity function of their MUC7 glycoprotein against bacterial invasion may be compromised in CRS patients.
Am J Rhinol Allergy. 2010 May-Jun;24(3):169-74. doi: 10.2500/ajra.2010.24.3462.
BACKGROUND: Although biofilms have been implicated in the pathogenesis of chronic rhinosinusitis (CRS), there is little evidence that their presence or absence has any effect on the outcomes of endoscopic sinus surgery (ESS). The aim of this study was to investigate the effect of biofilms on postsurgical outcomes after ESS.
METHODS: A prospective, blinded study of 51 consecutive patients undergoing ESS for CRS was conducted. Preoperatively, patients assessed their symptoms using internationally accepted standardized symptom scoring systems and quality-of-life (QOL) measures, i.e., the 10-point Visual Analog Scale (VAS), Sino-Nasal-Outcome-Test 20, and global severity of CRS. Their sinonasal mucosa was graded using the Lund-Kennedy scale and the extent of radiological disease on computed tomography scans was scored using the Lund-McKay scale. Random sinonasal tissue samples were assessed for biofilm presence using confocal laser microscopy. At each postoperative visit, patients reassessed their sinus symptoms and completed QOL measures. Postsurgical state of their sinonasal mucosa was graded endoscopically.
RESULTS: Bacterial biofilms were found in 36 of 51 (71%) CRS patients. Patients with biofilms presented with significantly worse preoperative radiology and nasendoscopy scores (p = 0.003 and 0.01, respectively). After a median follow-up period of 16 months postsurgery, biofilm-positive patients had statistically worse sinus symptoms (VAS, p = 0.002) and worse nasendoscopy scores (p = 0.026). They also required extra postoperative visits and multiple antibiotic treatments deviating from the standard postoperative care required by biofilm-negative patients.
CONCLUSION: This study has shown that patients with biofilms have more severe disease preoperatively and persistence of postoperative symptoms, ongoing mucosal inflammation, and infections. This study strengthens the evidence for the role that biofilms may play in recalcitrant CRS.
Otolaryngol Clin North Am. 2010 Jun;43(3):473-87, vii. doi: 10.1016/j.otc.2010.02.020.
Innate immunity is an exciting area of research in rhinology because emerging evidence suggests that abnormal local immune responses, rather than pathogen-specific adaptive immunity, may play a more important role in the pathogenesis of chronic rhinosinusitis (CRS). This article reviews important recent research regarding the innate immune system and CRS, with particular focus on the role of pattern recognition receptors, antimicrobial peptides and biofilms, epithelial ciliary function, cystic fibrosis, and cigarette smoking, and on areas for future research and therapy.
J Otolaryngol Head Neck Surg. 2010 Jun;39(3):217-31.
INTRODUCTION: There has been an explosion in the understanding of the mechanisms of chronic sinonasal inflammation. Multiple approaches to control and modify the inflammatory reaction in chronic rhinosinusitis have led to many new agents being introduced topically to the sinonasal cavities. This article aims to provide an evidence-based approach to the science behind topical management of sinonasal disease.
METHODS: The literature on delivery device, position, surgical state, and pharmaceutical and mechanical concepts of topical therapy to the paranasal sinuses is reviewed.
RESULTS: High-volume irrigation under positive pressure and in head-down positions is important for effective delivery and mechanical action of topical solutions. Unoperated paranasal sinuses appear to receive very limited topical therapy. Enhanced steroid therapy and surfactants appear to be the most promising pharmaceutical approaches. Future novel therapies may include enhancers of the innate immune system. The effect of antibiotic additives is difficult to establish as this might be treating a disease-modifying state rather than the underlying pathology.
CONCLUSIONS: Topical therapies, applied after surgery, are likely to represent the mainstay of future management for chronic inflammatory rhinosinusitis.
J Laryngol Otol. 2010 May;124(5):510-4. doi: 10.1017/S0022215109992398. Epub 2009 Dec 11.
BACKGROUND: A variety of treatment modalities are currently used to treat recurrent respiratory papillomatosis. We aimed to study the efficacy of radiofrequency cold ablation (coblation) for the treatment of laryngotracheal recurrent respiratory papillomatosis, by comparing treatment intervals for coblation and CO2 laser vaporisation.
METHOD: Retrospective case series of adult patients with advanced laryngotracheal recurrent respiratory papillomatosis.
RESULTS: Six patients were treated for at least two years by CO2 laser vaporisation with or without intralesional cidofovir. All six subsequently underwent treatment with radiofrequency coblation with or without intralesional cidofovir. Coblation resulted in longer periods between interventions, compared with CO2 laser (p = 0.03).
CONCLUSION: Radiofrequency coblation appears to be an attractive alternative technique to CO2 laser for the surgical treatment of advanced laryngotracheal papillomata.
Am J Rhinol Allergy. 2009 Nov-Dec;23(6):556-61. doi: 10.2500/ajra.2009.23.3413.
BACKGROUND: Conclusive evidence exists that biofilms are present on the mucosa of chronic rhinosinusitis (CRS) patients. Less is known about the species constituting these biofilms. This study developed a fluorescence in situ hybridization (FISH) protocol for characterization of bacterial and fungal biofilms in CRS.
METHODS: Fifty CRS patients and 10 controls were recruited. Bacteria FISH probes for Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa and a universal probe for fungi were applied to sinus mucosal specimens and then analyzed using confocal scanning laser microscopy.
RESULTS: Thirty-six of 50 CRS patients had biofilms present in contrast to 0/10 controls, suggesting a role for biofilms in the pathogenesis of this disease. S. aureus was the most common biofilm-forming organism. Eleven of 50 CRS patients had characteristic fungal biofilms present.
CONCLUSION: This is the largest study of biofilms in CRS. It has validated mucosal tissue cryopreservation for delayed biofilm analysis. Fungal biofilms have been identified and the importance of S. aureus biofilms in the polymicrobial etiology of CRS is highlighted.
Laryngoscope. 2010 Feb;120(2):427-31. doi: 10.1002/lary.20705.
OBJECTIVES/HYPOTHESIS: Biofilms are increasingly recognized as having an etiological role in chronic rhinosinusitis (CRS). Research into biofilms in CRS currently relies on microscopic imaging techniques, none of which are universally accepted. This study compares LIVE/DEAD BacLight (Invitrogen Corp., Carlsbad, CA) staining and fluorescence in situ hybridization (FISH), both utilizing the confocal scanning laser microscope (CSLM) for biofilm determination and characterization in CRS patients.
STUDY DESIGN: Prospective study.
METHODS: Twenty CRS patients undergoing endoscopic sinus surgery were recruited for the study. Sinus mucosal tissue harvested at the time of surgery underwent both the BacLight/CSLM and FISH/CSLM protocols for biofilm determination and characterization.
RESULTS: Combining the results of both protocols, 18/20 (90%) patients had bacterial biofilms demonstrable on at least one modality. The high biofilm detection rate combining the two techniques suggests the prevalence of biofilms in CRS may be greater than previously reported. The protocols had equivalent results in 15/20 patients. Using the differences observed in the remaining five patients, we can highlight the most appropriate use for each technique.
CONCLUSIONS: BacLight/CSLM and FISH/CSLM are complementary techniques for biofilm determination and characterization. Both protocols are suited to different research areas and the selection of technique used should be based on the specific objectives of the research protocol. In this way we can utilize the advantages of each technique to facilitate effective research.
Am J Rhinol Allergy. 2009 Jan-Feb;23(1):33-5. doi: 10.2500/ajra.2009.23.3255.
BACKGROUND: The Lund-MacKay score (LMS) is the standard for communicating radiological extent of chronic rhinosinusitis in research. However, retrospective analyses are often hindered by a substantial lack of radiological data. Calculating LMS from radiologists' reports may overcome this but has not been formally validated.
METHODS: Twenty South Australian and 20 Texan patients with varying degrees of sinus disease were randomly chosen to undergo analysis. CT-derived LMSs were calculated directly by two expert rhinologists at each institution and compared with scores derived solely from accompanying radiology reports by two blinded reviewers.
RESULTS: The total LMS obtained via the expert rhinologists correlated very highly with that obtained from radiology reports (Spearman rank correlation, 0.75-0.88; p < 0.001). However, when individual sinuses were specifically analyzed, the correlation was highly variable.
CONCLUSION: The results show that in both South Australian and Texan tertiary rhinology centers, radiologists' reports can be reliably used to calculate the total LMS.
Am J Rhinol. 2008 Nov-Dec;22(6):560-7. doi: 10.2500/ajr.2008.22.3232.
BACKGROUND: Biofilms have been shown to be resistant to conventional antibiotic treatment. This study uses a sheep biofilm model developed by our department to investigate several novel topical anti-biofilm treatments.
METHODS: Staphylococcal biofilms were grown in 54 sheep frontal sinuses over 8 days: Each sinus was randomized to (1) no intervention, (2) single mupirocin flush, (3) regular 12-hourly mupirocin flushes for 5 days, (4) Citric Acid Zwitterionic Surfactant (CAZS) via hydrodebrider, (5) gallium nitrate, (6) CAZS with gallium nitrate, (7) CAZS with mupirocin, and (8) saline regular flushes. Sheep were sacrificed and the sinus mucosa harvested 1 or 8 days after treatment to assess treatment and any biofilm regrowth. Confocal scanning laser microscopy was used to confirm the presence or absence of biofilms, and the extent of biofilm reduction was quantitated using fluorescent in situ hybridization and colony forming unit counts.
RESULTS: In the control sheep biofilm coverage averaged 31.7%. Saline and mupirocin b.d. washes for 5 days had 23% and 0.84% coverage, respectively, when harvested on day 8. A single mupirocin and gallium wash had 7.7% and 16.2% on day 1 and 5.88% and 16.0% on day 8. CAZS with hydrodebrider had 6.66% on day 1 but 21.95% on day 8 whereas CAZS with hydodebrider and gallium had 13.3% on day 8.
CONCLUSION: This study shows that regular treatment with mupirocin produced the most marked reduction in biofilm surface area coverage (0.84% and 1.25%) with sustained effects over the 8-day follow-up period.
Laryngoscope. 2008 Sep;118(9):1677-80. doi: 10.1097/MLG.0b013e31817aec47.
OBJECTIVES/HYPOTHESIS: To examine the efficacy and tolerability of topical mupirocin for the management of surgically recalcitrant chronic rhinosinusitis (CRS) associated with Staphylococcus aureus infection.
STUDY DESIGN: Prospective open-label pilot study.
METHODS: Patients with surgically recalcitrant CRS who had positive nasendoscopically guided cultures for Staphylococcus aureus were treated with twice daily nasal lavages containing 0.05% Mupirocin and lactated ringers salts. The duration of treatment was 3 weeks. Patients were assessed before and after treatment in terms of nasendoscopic findings, microbiology results, and Sinonasal Outcome Test (SNOT-20) and visual analogue scale questionnaires.
RESULTS: Fifteen of 16 patients had improved nasendoscopic findings after treatment. Twelve of 16 patients noted overall symptom improvement. Fifteen of 16 patients had negative swab results for Staphylococcus aureus after treatment. Only minimal adverse effects were experienced.
CONCLUSIONS: Nasal Lavage with 0.05% Mupirocin may represent an effective and well tolerated alternative treatment for postsurgical recalcitrant CRS.
Am J Rhinol. 2008 Jan-Feb;22(1):1-6. doi: 10.2500/ajr.2008.22.3119.
BACKGROUND: Although the existence of biofilms on the sinus mucosa of patients with chronic rhinosinusitis (CRS) is now well established, the role that these structures play remains unclear. It is thought that biofilms may contribute to the recalcitrant and persistent nature that characterizes CRS, but little research exists documenting the effect that they have on postoperative mucosal outcomes. This article presents a retrospective analysis of sinus surgical patients and correlates the presence of biofilms with mucosal outcomes. This study was performed to evaluate the role that bacterial biofilms have on post-sinus surgical outcomes.
METHODS: A retrospective analysis of prospectively collected data was performed on 40 patients undergoing endoscopic sinus surgery (ESS) for CRS. Preoperative demographic, clinical, and radiologic data were recorded from each patient and, intraoperatively, sinus culture specimens and mucosal samples were obtained for microbiological and microscopic examination. Biofilm determination was performed using confocal scanning laser microscopy. Postoperatively, patients were followed up for a minimum of 8 months with endoscopic evaluation of their sinonasal mucosa. The presence of ongoing symptoms was recorded also.
RESULTS: Bacterial biofilms were found in 20 (50%) of the 40 CRS patients. Patients with biofilms had significantly worse preoperative radiological scores and, postoperatively, had statistically worse postoperative symptoms and mucosal outcomes. The only other factor that was statistically related to an unfavorable outcome was the presence of fungus at the time of surgery. In this study the presence of polyps, eosinophilic mucin, or pus was not related to poor outcomes.
CONCLUSION: This retrospective study showed that bacterial biofilms and fungus were correlated with the persistence of postoperative symptoms and mucosal inflammation after sinus surgery for CRS. This provides evidence that biofilms indeed may play an active role in perpetuating inflammation in CRS patients and may explain the recurrent and resistant nature of this disease. Therapies targeted at removing biofilms may be important in the management of recalcitrant CRS.
Laryngoscope. 2008 May;118(5):895-901. doi: 10.1097/MLG.0b013e31816381d4.
OBJECTIVE/HYPOTHESIS: The diverse antipathogenic action of lactoferrin has been well characterized. In addition, it is the human body's only known antimicrobial peptide with antibiofilm properties. The purpose of this study was to examine the nasal mucosal expression of lactoferrin in the biofilm-mediated disease, chronic rhinosinusitis (CRS).
STUDY DESIGN/METHODS: Nasal biopsies from 41 CRS patients and 21 healthy controls were analyzed using confocal scanning laser microscopy (CSLM) and scanning electron microscopy (SEM) for the presence of biofilms. The messenger ribonucleic acid (mRNA) and protein level of lactoferrin in this tissue were also determined by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively.
RESULTS: Lactoferrin expression in chronic rhinosinusitis patients at both mRNA and protein level was downregulated relative to controls. Biofilm-positive CRS patients showed a much greater reduction in lactoferrin expression than biofilm-negative patients; mRNA median fold change biofilm positive = 0.03 (interquartile range 0.005-0.15) and biofilm-negative CRS median fold change = 0.49 (interquartile range 0.15-0.81) with median lactoferrin protein expression biofilm-positive patients' median lactoferrin protein expression = 32.58 ng/mL (interquartile range 8.67-59.9 ng/mL) and biofilm-negative patients' median lactoferrin expression = 114.40 ng/mL (interquartile range 75.41-163.1 ng/mL).
CONCLUSIONS: Genetic, transcriptional, or translational deficiencies in lactoferrin synthesis may reduce the functional level of this important antimicrobial/antibiofilm peptide in the nasal secretions of CRS patients, predisposing certain individuals to bacterial colonization, biofilm development, and recalcitrant sinus disease.
Laryngoscope. 2008 Mar;118(3):535-40. doi: 10.1097/MLG.0b013e31815bf2e3.
BACKGROUND: It has been postulated that bacterial biofilms are involved in the pathogenesis of chronic rhinosinusitis (CRS). Biofilms present on sinus mucosa are difficult to eradicate with conventional antibiotic therapy and are thought to provide a nidus for recurrent infection. Topical delivery of antibiotics via nasal irrigation may present a way of delivering high concentrations of antibiofilm agents with potentially low systemic absorption and side effects. This study investigates the effectiveness of mupirocin and two other antibiotics, ciprofloxacin and vancomycin, on established in vitro biofilms of Staphylococcus aureus isolated from patients with CRS.
METHODS: S. aureus American Type Culture Collection 25923 and 12 clinical isolates were investigated for their ability to form biofilms in an in vitro setting using a 96 well microtiter crystal violet (CV) plate assay and confocal scanning laser microscopy (CSLM). Antimicrobial susceptibility tests to determine minimum inhibitory concentrations were performed on planktonic and biofilm forming strains. In addition, established biofilms were subjected to the antimicrobial agents at a twofold dilution series. A CV analysis of biofilm mass was performed after 1 and 24 hours of treatment, and minimum biofilm inhibition concentrations at 50% (MIB50) and 90% (MIB90) biofilm inhibition were recorded.
RESULTS: With use of a 96-well microtiter plate CV assay, 8 of the 12 clinical isolates formed mature biofilms after 8 days of culture. These results correlated with findings from CSLM analysis of in vitro biofilms grown on Permanox chamber slides. Increased antimicrobial resistance was observed in the biofilm isolates when compared with planktonic counterparts. Mupirocin was capable of reducing biofilm mass by greater than 90% at concentrations of 125 mug/mL or less in all S. aureus isolates. Ciprofloxacin and vancomycin were largely ineffective in attaining MIB90 concentrations within safe dosage ranges.
CONCLUSIONS: The topical application of mupirocin via nasal irrigation may be useful in eliminating S. aureus biofilms present on the sinus mucosa of patients with CRS and may offer an additional treatment to patients with recalcitrant sinusitis.
Laryngoscope. 2007 Nov;117(11):2030-5. doi: 10.1097/MLG.0b013e31812e01ab.
OBJECTIVE/HYPOTHESIS: Antimicrobial peptides, such as lactoferrin, are an important component of the innate immune system. They offer the body a first line defense against a wide range of invading pathogens. The diverse antipathogenic action of lactoferrin has been well characterized; however, the role that this peptide plays in chronic conditions such as rhinosinusitis remains largely unknown. This study aims to examine the level of lactoferrin expression in the nasal mucosa of patients with chronic rhinosinusitis (CRS).
STUDY DESIGN/METHODS: Nasal biopsies of 85 chronic rhinosinusitis patients, subclassified into allergic fungal sinusitis (AFS), nonallergic fungal eosinophilic sinusitis (NAFES), nonallergic, nonfungal eosinophilic sinusitis (NANFES), and CRS were studied by quantitative real-time reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay for their expression of lactoferrin at an mRNA and protein level, respectively.
RESULTS: All groups of patients with CRS showed a decrease in lactoferrin mRNA expression relative to controls (median fold-change of CRS relative to controls, 0.1550; AFS, 0.1800; NANFES, 0.1900; and NAFES, 0.2100). All groups also showed a decreased expression of lactoferrin protein (controls, 163.3 ng/mL; CRS, 82.19 ng/mL; AFS, 104.1 ng/mL; NANFES, 118.9 ng/mL; and NAFES, 74.33 ng/mL). The most significant reduction was evident in the CRS subgroup as well as in patients with nasal polyposis at the time of surgery.
CONCLUSIONS: This is the first study of its kind to objectively examine lactoferrin expression in the nasal mucosa of CRS patients. We report a reduction in the expression of this important antimicrobial peptide at both the mRNA and protein level. Such a defect in the innate immune system may explain the predisposition of certain individuals to develop CRS and nasal polyposis, providing further insight into the pathogenesis of such conditions.
Am J Rhinol. 2007 May-Jun;21(3):339-45. doi: 10.2500/ajr.2007.21.3032.
BACKGROUND: Bacterial biofllms have been shown in chronic diseases such as cystic fibrosis, cholesteatoma, and otitis media with effusion. Recently, their detection on the mucosal tissue of sinusitis patients has implicated them in the pathogenesis of this condition. We present an animal model using sheep experimentally infected with Staphylococcus aureus to study the possible association between biofilm and sinusitis.
METHODS: Twenty-four sheep underwent bilateral endoscopic sinus surgery to identify their frontal ostia. The frontal sinuses were treated in one of the following ways according to preoperative randomization: (1) ostium left patent, (2) ostium left patent and bacteria instilled, (3) ostium occluded, or (4) ostium occluded and bacteria instilled. The frontal mucosa was harvested at day 7 and examined for biofilm presence using confocal scanning laser microscopy (CSLM) as well as scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
RESULTS: All three modalities showed different rates of biofilm detection. Three-dimensional structures that could be interpreted as biofilms were documented in 86% (n = 36) of the sinuses analyzed using SEM. These structures were seen in all four study groups. The detection rate using the other two modalities was much lower with CSLM, showing biofilms in 48% (n = 20) and TEM in only 29% (n = 12) of the sinuses analyzed. Unlike SEM, these two modalities only detected bacterial biofilms in sinuses randomized to bacterial instillation.
CONCLUSION: The demonstration of bacterial biofilms in this animal model of sinusitis further supports the hypotheses that biofilms may play a role in the pathogenesis of this condition. There is an obvious discrepancy in the sensitivity and specificity of biofilm detection using the three modalities mentioned. CSLM appears to be the most objective technique. The inherent flaws, sampling error, and subjectivity involved in SEM and TEM make these less reliable in documenting biofilm existence.
Laryngoscope. 2007 Jul;117(7):1302-6. doi: 10.1097/MLG.0b013e31806009b0.
OBJECTIVES: The recent detection of bacterial biofilms on the sinus mucosa of patients with chronic rhinosinusitis (CRS) has implicated biofilms in the pathogenesis of this condition. Electron microscopy has been the main modality used to document the presence of biofilms on sinus tissue, however, it has inherent problems associated with tissue preparation and sampling. Recently, Confocal Scanning Laser Micrsocopy (CSLM) has emerged as a noninvasive, nondestructive technique for the analysis of biofilms. This study used CSLM as the means of investigating biofilm presence in CRS patients.
STUDY DESIGN AND METHODS: A prospective study comparing the presence of bacterial biofilms on the sinus mucosa of CRS and control patients was conducted using CSLM. Thirty eight CRS patients undergoing endoscopic sinus surgery and nine control patients were enrolled in this study. Demographic and clinical information was recorded from each patient and intraoperatively, sinus culture specimens and mucosal samples were obtained for microbiologic and microscopic examination.
RESULTS: Using previously documented CSLM criteria, bacterial biofilms were found in 17 (44%) of the 38 CRS patients. No biofilm structures were evident in any of the controls. Patients having undergone previous sinus surgery seemed to have a higher incidence of biofilms compared with the incidence for those undergoing their first procedure. The difference however was not statistically significant. No correlation between positive bacterial cultures and biofilm presence was observed.
CONCLUSIONS: The CSLM detection of biofilms in CRS patients and their absence in controls further supports the hypothesis that biofilms may play a role in the pathogenesis of CRS. This study's lower reported incidence of biofilms compared with that of previous studies might reflect the increased accuracy of biofilm detection with CSLM.
Laryngoscope. 2007 Mar;117(3):411-4. doi: 10.1097/MLG.0b013e31802c0707.
BACKGROUND: Previous studies have suggested that chronic rhinosinusitis may result from a hypersensitivity response of the nasal mucosa to the presence of fungal antigens or staphylococcal superantigens in the nasal mucus. Both of these groups of antigens are present so frequently in the nasal mucus of patients with chronic rhinosinusitis that their presence together is likely to be a common event.
OBJECTIVE: The objective of this study was to determine whether the combined presence of fungal antigens and staphylococcal superantigens exert a synergistic proinflammatory effect on peripheral blood lymphocytes from patients with chronic rhinosinusitis.
METHODS: Peripheral blood lymphocytes were extracted from patients with chronic rhinosinusitis with and without nasal polyposis (n = 7 for both groups) and normal controls (n = 7). These cells were cultured for 48 hours after the addition of fungal extracts (Aspergillus and Alternaria), staphylococcal superantigen type B (SEB), or a combination of these two antigens. Real-time polymerase chain reaction was used to determine the level transcription of interleukinL-5 and interferon-gamma genes.
RESULTS: Fungal extracts alone resulted in minimal changes in the levels of cytokine expression in peripheral blood lymphocytes. SEB increased the expression of IFN-gamma, and this effect was magnified by the addition of SEB and fungal extracts together to the culture medium. There were no differences in the magnitude of responses seen in patients with and without polyps nor between patients with chronic rhinosinusitis and normal controls.
CONCLUSION: SEB exerts a powerful proinflammatory effect on peripheral blood lymphocytes and fungal extracts may act synergistically to promote this action.
Chron Respir Dis. 2004;1(4):229-31. doi: 10.1191/1479972304cd042cr.
We report here an unusual case of a 25-year old male with juvenile onset recurrent respiratory papillomatosis who developed an infestation of papillomata 'papillomatization' of an old abscess cavity that, when removed, was coincidently found to contain a 2 cm well differentiated squamous cell carcinoma. The abscess cavity had been caused by a previous Fusobaterium necrophorum infection that probably developed as a result of septic emboli from his internal jugular veins. This once common but now rare occurrence was first reported by Dr Lemierre in 1936 (Lemierre syndrome).