Cell viability measured by cytotoxicity assay as a biomarker of chronic obstructive pulmonary disease exacerbation: a prospective cohort study

Background and objective Acute severe exacerbation of chronic obstructive pulmonary disease (COPD) is related to high mortality; however, a robust blood biomarker for COPD exacerbation has not been established. Impaired clearance of apoptotic cells is a possible pathogenesis of COPD development. We evaluated the clinical utility of serum cell viability as a predictive biomarker for COPD exacerbation. Methods Using serum from patients with stable COPD, cell viability was analyzed with a lactate dehydrogenase (LDH) assay. The patients were divided into low (optical density [OD] > 0.737) and high (OD ≤ 0.737) cell viability groups. Poisson regression analyses estimated the prognostic impact for COPD exacerbation, and a Cox proportional hazard model determined the impact on mortality. Results Among 162 patients, 47 were excluded due to follow-up loss within 1 year, asthma or combined interstitial lung disease diagnosis, and unsuitable cell viability measurements. The median follow-up duration was 6.3 years; 61 (53%) patients experienced at least one moderate or severe exacerbation, and 21 (19.7%) died. Patients in the low cell viability group were older, more likely to have poor quality of life and had a lower proportion of the non-exacerbator phenotype than those in the high cell viability group. The low cell viability group had a higher risk of moderate (incidence rate ratio [IRR], 1.58; p = 0.049) and severe (IRR, 2.69; p = 0.001) exacerbations and mortality (adjusted hazard ratio, 5.79; p = 0.016). Conclusion We identified that low cell viability, measured with a serum LDH cytotoxicity assay, was associated with severe COPD exacerbation and higher mortality in patients with COPD.