Cytokine Biomarkers of Exacerbations in Sputum From Patients With Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study

Background We determined the relationships between cytokine expression in sputum and clinical data to characterize and understand chronic obstructive pulmonary disease (COPD) exacerbations in people with COPD.Methods We measured 30 cytokines in 936 sputum samples, collected at stable state and exacerbation visits from 99 participants in the Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) study (ClinicalTrials.gov NCT01360398). We determined their longitudinal expression and examined differential expression based on disease status or exacerbation type.Results Of the cytokines, 17 were suitable for analysis. As for disease states, in exacerbation sputum samples, interleukin (IL) 17A, tumor necrosis factor alpha (TNF-alpha), IL-1 beta, and IL-10 were significantly increased compared to stable state sputum samples, but a logistic mixed model could not predict disease state. As for exacerbation types, bacteria-associated exacerbations showed higher expression of IL-17A, TNF-alpha, IL-1 beta, and IL-1 alpha. IL-1 alpha, IL-1 beta, and TNF-alpha were identified as suitable biomarkers for bacteria-associated exacerbation. Bacteria-associated exacerbations also formed a cluster separate from other exacerbation types in principal component analysis.Conclusions Measurement of cytokines in sputum from COPD patients could help identify bacteria-associated exacerbations based on increased concentrations of IL-1 alpha, IL-1 beta, or TNF-alpha. This finding may provide a point-of-care assessment to distinguish a bacterial exacerbation of COPD from other exacerbation types. Measuring 30 cytokines in 936 sputum samples from patients with chronic obstructive pulmonary disease, we observed significant increases (IL-17A, TNF-alpha, IL-1 beta, IL-10) between stable and exacerbation states. We also identified a combination of cytokines (IL-1 alpha, IL-1 beta, or TNF-alpha) as suitable biomarkers for bacteria-associated exacerbations.