• Kerry Day, Kristoffer Ostridge, Joy Conway, Doriana Cellura, Alastair Watson, Cosma Mirella Spalluto, Karl J Staples, Bruce Thompson, and Tom Wilkinson.
• Faculty of Medicine, University of Southampton, Southampton; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton. Electronic address: kg5n14@soton.ac.uk.
• Chest. 2021 Apr 1; 159 (4): 1391-1399.

BackgroundSmall airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline.Research QuestionIs SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation?Study Design And MethodsThirty-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.ResultsSacin 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).InterpretationIncreased 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.Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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