Interrelationships between small airways dysfunction, neutrophilic inflammation and exacerbation frequency in COPD.

Abstract Background Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline. Research Question Is small airways disease a key feature of frequent COPD exacerbators and is this related to airway inflammation? Study Design and Methods Thirty nine COPD subjects defined as either frequent exacerbators ( ≥ 2 exacerbations per year, n = 17) and infrequent exacerbators (≤1 exacerbation per year, n = 22) underwent Forced Oscillation Technique (R5-R19, AX), multiple breath nitrogen washout (Scond, Sacin), plethysmography (RV/TLC), single breath transfer factor (TLCO), spirometry (FEV1%, FEV1/FVC) and paired inspiratory – expiratory CT scans to ascertain small airways disease. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions. Results Acinar ventilation heterogeneity (Sacin) was significantly higher in COPD FE compared to IE (P = .027). In the FE group, markers of SAD were strongly associated with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, rho = 0.560), RV/TLC (P = .004, r = 0.730) and the mean lung density of the paired CT scans (P = .018, r = 0.639). Interpretation Increased acinar ventilation heterogeneity may be a consequence of previous exacerbations or highlight a group of patients prone to exacerbations. Measures of SAD were strongly associated with neutrophilic inflammation in the small airways of FE supporting the hypothesis that frequent exacerbations are associated with small airway disease related to increased cellular inflammation.