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

## TL;DR

Low cell viability measured in blood is linked to severe COPD flare-ups and higher death rates in patients.

## Contribution

A new blood biomarker for COPD exacerbation risk is identified using a cytotoxicity assay.

## Key findings

- Low cell viability was associated with increased risk of moderate and severe COPD exacerbations.
- Patients with low cell viability had a higher mortality rate.
- Cell viability was measured using a lactate dehydrogenase assay in serum.

## Abstract

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.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. 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 (range 0.7–11 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).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.

The online version contains supplementary material available at 10.1038/s41598-025-14536-5.