Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

Abstract

Background: It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma.

Objective: We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status.

Methods: We collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines. Inflammatory cytokines were investigated using a Th1/Th2 assay including 14 chemokines and cytokines; tissue concentrations were normalized according to tissue weight and total protein concentration. Individual cytokines and multivariate inflammatory profiles were compared between biopsy sites and between patients and controls.

Results: We found significantly higher concentrations of Th2 cytokines in nasal polyps compared to inferior turbinate and bronchial biopsies. In addition, we showed that the inflammatory profile of nasal polyps and bronchial biopsies correlated significantly (p<0.01). From the Th2 cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma.

Conclusion: Our findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally, this study indicates for the first time that nasal polyps potentially play an important role in the airway inflammation rather than being a secondary phenomenon.

Fig 1. Inflammatory cytokines in bronchial biopsies (MCP-4, IL-5, IL-13 and TARC) in CRSwNP patients and controls, stratified by asthma severity.

Log transformed data, concentrations in pg/mL. I = Intermittent; MiP = Mild persistent; MoP = Moderate persistent; SP = Severe persistent. P-values represent comparison by Kruskal-Wallis test. In this analysis we included biopsies from controls with asthma that were not included in the inter-group analyses. This analysis indicates that bronchial inflammation increases with increasing asthma-severity.

Fig 2. Concentration of Th1 and Th2 cytokines in nasal polyps, ITs and bronchial biopsies in CRSwNP patients.

A: Th1 cytokines. B: Th2 cytokines. Log transformed data, concentrations in pg/mL. NP = nasal polyp, BB = bronchial biopsy, IT = inferior turbinate. P-values represent comparison by a paired Wilcoxon signed rank test. Both CRSwNP patients with and without asthma are included in this analysis. All Th2 cytokines were increased in the nasal polyps compared to the bronchii; this difference was not seen for Th1 cytokines.