Clinical Indicators for Asthma-COPD Overlap: A Systematic Review and Meta-Analysis

Background: Some clinical indicators have been reported to be useful in differentiating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) from pure asthma/COPD, but the results were inconsistent. This study aims to evaluate the diagnostic value of these indicators for ACO. Methods: Databases of PubMed, EMBASE, Ovid and Web of Science were retrieved. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated in random-effects models. Results: 48 eligible studies were included. The pooled results indicated, compared with pure asthma, ACO patients had lower levels of forced expiratory volume in the first second (FEV 1 )% predicted (pred) (SMD=− 1.09, 95% CI − 1.3 to − 0.87), diffusion lung capacity for carbon monoxide (DLCO)% pred (SMD=− 0.83, 95% CI − 1.24 to − 0.42), fractional exhaled nitric oxide (FeNO) (SMD=− 0.23, 95% CI − 0.36 to − 0.11), and higher levels of induced sputum neutrophil (SMD = 0.51, 95% CI 0.21 to 0.81), circulating YKL-40 (SMD = 0.96, 95% CI 0.27 to 1.64). However, relative to COPD alone, ACO patients had higher levels of FEV 1 % pred (SMD = 0.15, 95% CI 0.05 to 0.26), DLCO% pred (SMD = 0.38, 95% CI 0.16 to 0.6), FeNO (SMD = 0.59, 95% CI 0.40 to 0.78), serum total immunoglobulin (Ig)E (SMD = 0.42, 95% CI 0.1 to 0.75), blood eosinophil (SMD = 0.44, 95% CI 0.29 to 0.59), induced sputum eosinophil (SMD = 0.62, 95% CI 0.42 to 0.83), and lower levels of induced sputum neutrophil (SMD=− 0.48, 95% CI − 0.7 to − 0.27), circulating YKL-40 (SMD=− 1.09, 95% CI − 1.92 to − 0.26). Conclusion: Compared with pure asthma/COPD, ACO patients have different levels of FEV 1 % pred, DLCO% pred, FeNO, serum total IgE, blood eosinophil, induced sputum eosinophil/neutrophil, and circulating YKL-40, which could be helpful to establish a clinical diagnosis of ACO. Keywords: asthma, asthma-COPD overlap, COPD, indicators, meta-analysis