Interrelationships Among Small Airways Dysfunction, Neutrophilic Inflammation, and Exacerbation Frequency in COPD

Published:November 24, 2020DOI:


      Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline.

      Research Question

      Is SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation?

      Study Design and Methods

      Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n = 17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n = 22) underwent the forced oscillation technique (resistance at 5 Hz minus 19 Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions.


      Sacin was significantly higher in the COPD FE group compared with the IFE group (P = .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, ρ = 0.560), residual volume to total lung capacity ratio (P = .004, r = 0.730), and the mean lung density of the paired CT scans (P = .018, r = 0.639).


      Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.

      Key Words


      AX (area of reactance), FE (frequent exacerbator), FOT (forced oscillation technique), HRCT (high-resolution CT), ICS (inhaled corticosteroids), IFE (infrequent exacerbator), MBNW (multiple breath nitrogen washout), MLD E/I (ratio of the mean lung density of expiration to inspiration), R5-R19 (resistance at 5 Hz minus 19 Hz), Sacin (acinar ventilation heterogeneity), SAD (small airways disease), Scond (conducting airways ventilation heterogeneity)
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