Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in study-defined asthma–COPD overlap and COPD: a systematic review and meta-analysis of comparative observational studies

Asthma–COPD overlap (ACO) is a descriptive clinical construct referring to patients exhibiting features of both asthma and chronic obstructive pulmonary disease (COPD). Because no universally accepted diagnostic criteria exist, clinical and inflammatory characteristics of study-defined ACO may vary across operational frameworks and disease phases. This systematic review and meta-analysis primarily compared the neutrophil-to-lymphocyte ratio (NLR) between study-defined ACO and COPD, with platelet-to-lymphocyte ratio (PLR) and other hematologic indices examined as secondary outcomes. We searched PubMed, Embase, Web of Science Core Collection and the Cochrane Library from inception to February 3, 2026. NLR was the primary search concept; PLR and other hematologic indices were secondary outcomes extracted from NLR-eligible studies. Four studies formed the primary stable-phase syntheses. One acute-exacerbation study was reported separately. Item-level risk of bias was assessed using the eight-item JBI checklist. We calculated standardized mean differences (SMDs), leave-one-out estimates and approximate 95% prediction intervals (PIs), and assessed influence, between-study variation and data-conversion assumptions. Five studies reported 437 patients with study-defined ACO and 1,000 with COPD. The primary stable-phase set comprised four studies (162 ACO and 592 COPD). NLR was significantly lower under the primary DerSimonian–Laird model (SMD, − 0.36; 95% CI, − 0.61 to − 0.12; P = 0.004; I² = 45%; 95% PI, − 1.26 to 0.54). All four NLR leave-one-out confidence intervals remained below zero. PLR was inconclusive (SMD, − 0.05; 95% CI, − 0.31 to 0.22; P = 0.740; 95% PI, − 1.08 to 0.99). Both prediction intervals included zero. This review synthesized group differences rather than diagnostic accuracy. NLR was significantly lower in study-defined stable-phase ACO than COPD in the primary random-effects analysis. Small-sample inference and estimated summaries limit the certainty of this finding. PLR findings were inconclusive. Both approximate prediction intervals crossed zero. These observational group comparisons do not establish diagnostic thresholds or incremental clinical utility. Not applicable.