A sputum 6-gene signature predicts airway inflammation endotypes and exacerbation frequency in chronic obstructive pulmonary disease.

Aim: To validate a sputum 6-gene signature (6GS), comprising of CLC , CPA , DNASE1L3 , IL-1B , ALPL and CXCR2 , for identifying different endotypes in chronic obstructive pulmonary disease. Methodology & results: Sputum cell CLC , CPA3 and DNASE1L3 gene expression correlated with eosinophil percentage, while IL-1B , ALPL and CXCR2 correlated with neutrophil percentage. Hierarchical cluster analyses of IL-1B , ALPL and CXCR2 , and CLC , CPA3 and DNASE1L3 , identified patient groups that differed in their sputum neutrophil and eosinophil levels, respectively. Multiple logistic regressions demonstrated that the 6GS could distinguish between eosinophil High and eosinophil Low patients, as well as neutrophil High and neutrophil Low , and could also predict exacerbation history. Conclusion: The 6GS may have applications in clinical practice or for stratifying patients for clinical trials.