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 eosinophilHigh and eosinophilLow patients, as well as neutrophilHigh and neutrophilLow, and could also predict exacerbation history. Conclusion: The 6GS may have applications in clinical practice or for stratifying patients for clinical trials.
Keywords: COPD; biomarker; endotypes; eosinophil; exacerbations; gene expression; neutrophil; sputum.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD is made up of a number of disease subgroups, which require different treatments. It is important for clinicians to be able to identify these subgroups. We have measured the activity levels of 6 sputum cell genes and demonstrated that the levels differ in two different subgroups of COPD, which are known to respond differently to treatment. We have also shown that the amount these genes are turned on allows us to identify patients who might suffer a worsening in their symptoms in the future.