Kerry Day1, Kristoffer Ostridge2, Joy Conway3, Doriana Cellura4, Alastair Watson4, Cosma Mirella Spalluto4, Karl J Staples5, Bruce Thompson6, Tom Wilkinson5. 1. Faculty of Medicine, University of Southampton, Southampton; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton. Electronic address: kg5n14@soton.ac.uk. 2. Faculty of Medicine, University of Southampton, Southampton; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton; Clinical Development, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. 3. Brunel University, London, England. 4. Faculty of Medicine, University of Southampton, Southampton. 5. Faculty of Medicine, University of Southampton, Southampton; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton. 6. Swinburne University of Technology, Melbourne, Australia.
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 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. RESULTS: 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). INTERPRETATION: 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.
BACKGROUND: 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 COPDpatients 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 breathnitrogen 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. RESULTS: 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). INTERPRETATION: 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.
Authors: Emma Ray; David Culliford; Helen Kruk; Kate Gillett; Mal North; Carla M Astles; Alexander Hicks; Matthew Johnson; Sharon Xiaowen Lin; Rosanna Orlando; Mike Thomas; Rachel E Jordan; David Price; Mita Konstantin; Tom M A Wilkinson Journal: NPJ Prim Care Respir Med Date: 2021-02-11 Impact factor: 2.871
Authors: Lee K Page; Karl J Staples; C Mirella Spalluto; Alastair Watson; Tom M A Wilkinson Journal: Front Immunol Date: 2021-03-24 Impact factor: 7.561