Association between underdiagnosed and overdiagnosed chronic obstructive pulmonary disease with all-cause mortality

Chronic obstructive pulmonary disease (COPD) underdiagnosis and overdiagnosis are common in clinical practice, but studies on their long-term prognosis remain limited. The study aimed to explore the all-cause mortality of underdiagnosed and overdiagnosed COPD in the general population.

This retrospective study analyzed participants from the National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 2007-2012 with quality-controlled demographic data, acceptable prebronchodilator spirometry, and all-cause mortality follow-up data. Airflow limitation was defined as forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) < lower limit of normal (LLN), and previously diagnosed COPD as physician-confirmed chronic bronchitis and/or emphysema. Participants were stratified into non-COPD (neither criterion), underdiagnosed COPD (airflow limitation without prior diagnosis), overdiagnosed COPD (prior diagnosis without airflow limitation), COPD (both criteria met). Logistic and Cox proportional hazards regressions were used to analyze risks of comorbidities/chronic respiratory symptoms and all-cause mortality between groups after covariates adjustment, respectively.

Of 24,661 participants (median follow-up 308 months), 84.6% were non-COPD, 9.5% underdiagnosed, 4.2% overdiagnosed, and 1.8% with confirmed COPD. Compared with non-COPD participants, overdiagnosed COPD participants had increased risks of comorbidities and chronic respiratory symptoms, while underdiagnosed participants had higher odds of chronic respiratory symptoms (all P<0.001). Both underdiagnosed [hazard ratio (HR): 1.25, 95% confidence interval (CI): 1.15-1.36, P<0.001] and overdiagnosed participants (HR: 1.18, 95% CI: 1.04-1.33, P=0.01) had higher all-cause mortality risk than non-COPD participants after covariates adjustment.

Participants with COPD underdiagnosis and overdiagnosis had increased disease burden and mortality risk. Spirometry screening facilitates the standardization of COPD diagnosis, which might reduce underdiagnosis and overdiagnosis. If spirometry is unavailable in resource-limited settings, underlying etiology-based intervention should be initiated early.