Utilization of Transcriptomic Profiling to Identify Molecular Markers Predicting Successful Recovery Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis.

Objectives: Successful recovery from chronic rhinosinusitis (CRS) following endoscopic sinus surgery (ESS) can be characterized by minimal presence of symptoms and absence of disease on endoscopy. However, molecular markers of surgical success remain to be characterized. These could allow for better tailoring of perioperative therapy.

Azithromycin Mechanisms of Action in CRS Include Epithelial Barrier Restoration and Type 1 Inflammation Reduction.

Objective: Previous in vitro transcriptomic profiling suggests azithromycin exerts its effects in patients with chronic rhinosinusitis (CRS) via modulation of type 1 inflammation and restoration of epithelial barrier function. We wished to verify these postulated effects using in vitro models of epithelial repair and in vivo transcriptional profiling.

Study Design: Functional effects of azithromycin in CRS were verified using in vitro models of wounding.

Response to intranasal probiotic supplementation in refractory CRS is associated with modulation of non-type 2 inflammation and epithelial regeneration.

Justification: We have previously documented that in individuals with chronic rhinosinusitis (CRS) refractory to surgery, intranasal application of live , a probiotic bacterium, improves sinus-specific symptoms, SNOT-22, and mucosal aspect on endoscopy, accompanied by a reduction in sinus pathogens and an increase in protective bacteria. The present work explores the molecular mechanisms underpinning these observations using transcriptomics of the sinus mucosa.

Method: Epithelial brushings collected prospectively as a sub-study of the clinical trial were used to probe epithelial responses to microbiome supplementation using a hypothesis-free bioinformatic analysis of gene expression analysis.

Low-dose and long-term azithromycin significantly decreases Staphylococcus aureus in the microbiome of refractory CRS patients.

Background: The sinonasal microbiome is believed to play an important role in the pathophysiology of refractory chronic rhinosinusitis (CRS). We evaluated changes in the microbiome following a 4-month course of low-dose azithromycin. Assessing microbiome alterations following such a treatment may help identify underlying mechanisms of this drug.

A pooling-based genome-wide association study implicates the p73 gene in chronic rhinosinusitis.

Background: p73 is a gene that may confer a genetic susceptibility to the development of chronic rhinosinusitis.

Objective: To verify an association between p73 and chronic rhinosinusitis, identified in a pooling-based genome-wide association study in a human population.

Methods: Prospective recruitment of 206 patients and 196 postal code-matched controls.

Molecular characterization of the polymicrobial flora in chronic rhinosinusitis.

Introduction: Conventional cultures have implicated Staphylococcus aureus (SA) and coagulase-negative Staphylococcus (CNS) as principal pathogens in chronic rhinosinusitis (CRS). These results are questioned by recent studies in which molecular probes implicate Haemophilus influenzae instead.

Objectives: To identify all bacterial species present on sinonasal mucosa using molecular culture (bacterial tag-encoded FLX amplicon pyrosequencing [bTEFAP]) and to compare them with those identified with conventional methods.

Polymorphisms in the tumour necrosis factor alpha-induced protein 3 (TNFAIP3) gene are associated with chronic rhinosinusitis.

Background: Factors conferring susceptibility to chronic rhinosinusitis remain unknown. However, advances in genomics offer powerful tools to explore this disorder. Tumour necrosis factor (TNF) is a crucial proinflammatory cytokine that exerts inflammatory and immunomodulatory activities important in host defense.