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Abstract

Rationale Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. Objectives Investigate biomarker expression in COPD exacerbations to identify biological clusters and determine biomarkers that recognise clinical COPD exacerbation phenotypes namely those associated with bacteria, viruses or eosinophilic airway inflammation. Methods Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biological phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. Measurements and Main Results 145 patients (101 men, 44 women) entered the study. 182 exacerbations were captured from 86 patients. Four distinct biological exacerbation clusters were identified. These were bacterial, viral or eosinophilic-predominant and a fourth was associated with limited changes in the inflammatory profile and was termed pauci-inflammatory. Of all exacerbations, 55%, 29% and 28% were associated with bacteria, virus and/or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1β (area under receiver-operator-characteristic-curve 0.89 (95% confidence interval 0.83 to 0.95), serum CXCL10 0.83 (0.70 to 0.96), and percentage peripheral eosinophils 0.85 (0.78 to 0.93) respectively. Conclusion The heterogeneity of the biological response of COPD exacerbations can be defined. Sputum IL-1β, serum CXCL10 and peripheral eosinophils are biomarkers of bacteria, virus or eosinophil associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.