Meta-analysis finds limited evidence for CPET variables in COPD mortality prediction

Chronic obstructive pulmonary disease (COPD) is a heterogeneous, progressive lung disorder. Despite its high prevalence, predicting clinical outcomes remains challenging. Various cardiopulmonary exercise testing (CPET) variables have been suggested as prognostic markers in COPD, but their role in clinical practice remains unclear. After registration in PROSPERO (ID CRD42024569879), a literature search of the Pubmed, Embase, Web of Science, Cochrane library and Scopus databases was carried out in August 2024. Study selection followed the PRISMA guidelines. Prospective and retrospective cohort studies evaluating associations between CPET variables and clinical outcomes in patients with COPD were included. Risk of bias was evaluated using the QUIPS tool. Data were extracted and synthesized narratively. A random-effects meta-analysis was planned if multiple studies reported comparable CPET variables, outcomes, and effect measures. Sixteen articles were included, three of which had an overall high risk of bias. Peak oxygen uptake (VOpeak) was consistently associated with mortality in univariate analyses, but its independent prognostic value in multivariable models was inconsistent. A random-effects meta-analysis of three studies evaluating VOpeak expressed as mL/kg/min did not demonstrate a statistically significant independent association with mortality (pooled HR 0.94, 95% CI 0.87-1.00; I = 63%). Ventilatory efficiency (VE/VCO) was identified as a significant prognostic marker in multiple studies. Other CPET-derived variables failed to show an independent association with mortality, although heterogeneity in metrics and adjustment strategies limited comparability. Evidence for other CPET-derived variables and for predicting severe acute exacerbations of COPD (AECOPD) or hospitalization was limited and inconsistent. CPET-derived variables, particularly VOpeak and VE/VCO, are associated with mortality in COPD, but evidence for their independent prognostic value and incremental benefit over established composite indices remains limited. Current data do not support routine use of CPET variables for prognostic stratification in COPD, apart from VOpeak as a marker of exercise capacity within the modified BODE index.