Association of Nonobstructive Chronic Bronchitis With All-Cause Mortality: A Systematic Literature Review and Meta-analysis

Background: The effect of nonobstructive chronic bronchitis (CB) on mortality is unclear. Research Question: Is nonobstructive CB associated with increased all-cause mortality? Study Design and Methods: We conducted a systematic literature review and meta-analysis to assess the association of nonobstructive CB and all-cause mortality. We searched for articles that included both CB and mortality in the title, abstract, or both in PubMed and EMBASE. We excluded studies in which participants demonstrated obstructive spirometry findings and studies in which CB and mortality were not defined. We used the Newcastle-Ottawa Quality Assessment Scale to assess study quality. We pooled adjusted hazard ratios (HRs) using the random effects model and inverse variance weighting. We conducted stratified analysis by the definition of CB and smoking status. We used Cochran's Q and I² to assess for heterogeneity. We assessed publication bias by visual inspection of a funnel plot. Results: Of 5,014 titles identified, eight fulfilled the inclusion and exclusion criteria. Overall nonobstructive CB was associated with all-cause mortality (HR, 1.37; 95% CI, 1.26-1.50) with no statistically significant heterogeneity (P =.14; I² = 29%). Nonobstructive CB was associated with increased mortality in studies that defined CB as any respiratory symptoms (broad definition; HR, 1.28; 95% CI, 1.10-1.48; I² = 0%) as well as in the rest of the studies (HR, 1.40; 95% CI, 1.26-1.56; I² = 37%). Nonobstructive CB was associated with increased mortality in ever smokers (HR, 1.49; 95% CI, 1.35-1.64; I² = 0%), but was not associated with increased mortality in never smokers (HR, 1.22; 95% CI, 0.90-1.66), and moderate heterogeneity was found (P =.10; I² = 49%). The funnel plot did not indicate evidence of a publication bias because it showed symmetrical distribution of studies. Interpretation: Nonobstructive CB is associated with increased all-cause mortality, and this association seems to be present only in current and former smokers. Further research should investigate whether this high-risk population may benefit from early therapeutic intervention. Trial Registry: PROSPERO; No.: CRD42021253596; URL: www.crd.york.ac.uk/prospero