• Suresh Garudadri, Prescott G Woodruff, MeiLan K Han, Jeffrey L Curtis, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Alejandro Comellas, Christopher B Cooper, Gerard Criner, Mark T Dransfield, Nadia N Hansel, Robert Paine, Jerry A Krishnan, Stephen P Peters, Annette T Hastie, Fernando J Martinez, Wanda K O'Neal, David J Couper, Neil E Alexis, and Stephanie A Christenson.
• Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, San Francisco, CA. Electronic address: sureshgarudadri@gmail.com.
• Chest. 2019 May 1; 155 (5): 908-917.

BackgroundChronic respiratory symptoms and exacerbation-like events are common among ever-smokers without airflow limitation on spirometry. The pathobiology of respiratory disease in this subgroup remains poorly defined, but may be due to underlying inflammation that overlaps with COPD or asthma. We hypothesized that symptoms, exacerbations, and functional measures of disease severity among smokers with preserved spirometry would be associated with markers of systemic inflammation, similar to what is reported in bone fide COPD, rather than elevated type 2 inflammation, which is often present in asthma.MethodsWe measured inflammatory markers associated with COPD (C-reactive protein [CRP], fibrinogen, soluble tumor necrosis factor receptors [sTNFRSF1A and sTNFRSF1B], and blood/sputum neutrophils) and type 2 inflammation (IgE and blood/sputum eosinophils) in smokers with preserved spirometry (postbronchodilator FEV1/FVC ≥ 0.70) from the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). We evaluated the relationship of these markers with respiratory symptom burden (dichotomized by a COPD assessment test score cutoff of 10, diagnosis of chronic bronchitis), exacerbations, 6-minute walk distance, and lung function on the basis of FEV1.ResultsCRP was associated with increased symptom burden (on the basis of COPD assessment test score and diagnosis of chronic bronchitis) and a greater number of exacerbations in the year before study enrollment. sTNFRSF1A was associated with symptom burden on the basis of COPD assessment test score. CRP and sTNFRSF1A levels negatively correlated with 6-minute walk distance. IgE and eosinophils were not associated with these outcomes.ConclusionsMarkers of inflammation including CRP and sTNFRSF1A are enriched among symptomatic smokers with preserved spirometry, suggesting an overlap with the underlying pathophysiology of COPD.Copyright © 2019 American College of Chest Physicians. All rights reserved.

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