Proteomic analysis of nasal mucus samples of healthy patients and patients with chronic rhinosinusitis.

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.

National Surgical Quality Improvement Program risk calculator validity in South Australian laryngectomy patients.

BACKGROUND: Assessing an individual patient's post-operative risk profile prior to laryngectomy for cancer is difficult. The American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) risk calculator was developed to better inform preoperative decision-making. The calculator uses patient-specific characteristics to estimate the risk of experiencing post-operative complications within 30 days of surgery. We investigated the ACS-NSQIP risk calculator's performance for Australian laryngectomy patients. METHODS: The ACS-NSQIP risk calculator was used to retrospectively calculate the 30-day post-operative predicted outcomes in patients who underwent laryngectomy for laryngeal, hypopharyngeal and thyroid cancers (with laryngeal involvement) in two institutions in South Australia. These data were compared against the actual mortality, morbidity, complications and length of stay (LOS) collected from a retrospective chart review. RESULTS: A total of 144 patients underwent surgical intervention for malignancies with laryngeal involvement. The median LOS was 25 days (range 13-197) compared to the predicted LOS of 6.5 days (range 3.5-12.5). Overall mortality was 2.78% with post-operative complications occurring in 63% of patients. The most common complication was wound infection, occurring in 33% of patients. Hosmer-Lemeshow plots demonstrated good agreement between predicted and observed rates for complications. CONCLUSION: The ACS-NSQIP risk calculator effectively predicted post-operative complication rates in South Australian laryngeal cancer patients undergoing laryngectomy. However, differences in predicted and actual LOS may limit the usefulness of the calculator's LOS predictions for Australian patients.

The role of biologics in chronic rhinosinusitis: a systematic review.

BACKGROUND: Chronic rhinosinusitis (CRS) refractory to medical and surgical treatment is challenging. It impacts patients' quality of life significantly. The pathophysiology of CRS has some similarities to allergic asthma and allergic rhinitis (AR) and includes eosinophilia, T-helper cell 2 cytokines, and local immunoglobilin E formation. Monoclonal antibody therapy has been used successfully in asthma and AR and more recently in CRS. Our was aim to systematically review the literature and identify the role of monoclonal antibodies (MAbs) in the treatment of CRS with polyps (CRSwNP) and without polyps (CRSsNP), especially with regard to comparability with current medical treatment, efficacy, and risk of complications. In addition, the role of surgery and biologics was evaluated. METHODS: We identified at total of 5341 relevant studies after a comprehensive database search. Six studies met the inclusion criteria, all 6 randomized, controlled trials. RESULTS: Treatment with omalizumab and mepolizumab demonstrated improvements in endoscopic nasal polyp score (EPS) and symptoms score in patients with CRSwNP when compared with placebo. Reslizumab reduced nasal polyp size in patients with raised intranasal interleukin-5 levels. Dupilumab treatment resulted in a 70% reduction in EPS compared with 20% in the placebo group (p < 0.001). These MAbs target different inflammatory markers involved in the pathophysiology of CRSwNP. None of the studies reported on CRSsNP or combined surgery with biologics. No severe adverse events were reported. CONCLUSION: Evidence demonstrates that use of MAbs leads to clinical improvement in CRSwNP. However, further research is required to determine their long-term effects, comparability to other medical treatments, and potential side effects.

The effect of neutrophil serine proteases on human nasal epithelial cell barrier function.

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.

Scoping review of pediatric tonsillectomy quality of life assessment instruments.

OBJECTIVES/HYPOTHESIS: Sleep-disordered breathing or recurrent tonsillitis have detrimental effects on the child's physical health and quality of life. Tonsillectomy is commonly performed to treat these common conditions and improve the child's quality of life. This scoping review aims to present a comprehensive and descriptive analysis of quality of life questionnaires as a resource for clinicians and researchers when deciding which tool to use when assessing the quality of life effects after tonsillectomy. STUDY DESIGN: A comprehensive search strategy was undertaken across MEDLINE (PubMed), CINAHL, Embase, and Cochrane CENTRAL. METHODS: Quality of life questionnaires utilized in studies investigating pediatric patients undergoing tonsillectomy for chronic tonsillitis or sleep-disordered breathing were included. Methodological quality and data extraction were conducted as per Joanna Briggs Institute methodology. RESULTS: Ten questionnaires were identified, consisting of six generic and four disease-specific instruments. The Pediatric Quality of Life Inventory was the most commonly utilized generic questionnaire. The Obstructive Sleep Apnea-18 was the most commonly utilized disease-specific questionnaire. CONCLUSIONS: This review identified a range of generic and disease-specific quality of life questionnaires utilized in pediatric patients who have undergone tonsillectomy with or without adenoidectomy for sleep-disordered breathing or chronic tonsillitis. Important aspects of each questionnaire have been summarized to aid researchers and clinicians in choosing the appropriate questionnaire when evaluating the quality of life effects of tonsillectomy. LEVEL OF EVIDENCE: NA Laryngoscope, 127:2399-2406, 2017.

Swallowing outcomes following primary surgical resection and primary free flap reconstruction for oral and oropharyngeal squamous cell carcinomas: A systematic review.

OBJECTIVES/HYPOTHESIS: Dysphagia is still a treatment-related morbidity, despite advances in treatment modalities for oral and oropharyngeal squamous cell carcinoma. This systematic review aimed to analyze the effects of swallowing outcomes of patients with oral or oropharyngeal squamous cell carcinoma treated with primary surgery with primary free flap reconstruction, with or without adjuvant therapy, for patients undergoing treatment with curative intent. STUDY DESIGN: A comprehensive search strategy was undertaken across MEDLINE, CINAHL, Embase, and Scopus. Gray literature was sought through Cochrane Central Register of Controlled Trials, MedNar, and ProQuest. METHODS: Studies included patients with oral cavity or oropharyngeal squamous cell carcinoma treated with primary surgery with primary free flap reconstruction. Swallowing function was the primary outcome, evaluated at 6 months or later following surgery. Methodological quality and data extraction was conducted as per the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument and standardized data extraction tool. RESULTS: Fifteen articles comprising eight cohort studies and seven case series were included. Postoperative radiotherapy and oropharyngeal resections were demonstrated to be associated with increased dysphagia. CONCLUSION: Advanced tumor-node-metastasis stage and use of adjuvant radiotherapy has been shown to have negative impacts on swallowing function. The majority of patients were able to have gastrostomy tubes removed at 6 months following curative therapy. Larger flap mass for the reconstruction of oral and oropharyngeal defects appeared to improve swallowing outcomes. A protocol for the identification of patients at high and low risk of developing dysphagia is proposed. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:1572-1580, 2016.