LAUSR

RATIONALE Early detection of COPD is a public health priority. Airflow obstruction is the single most important risk factor for adverse COPD outcomes, but spirometry is not routinely recommended for screening. OBJECTIVE To describe the burden of subclinical airflow obstruction (SAO) and to develop a probability score for SAO to inform potential detection and prevention programs. METHODS Lung function and clinical data were harmonized and pooled across 9 US general population cohorts. Adults with respiratory symptoms, inhaler use, or prior diagnosis of COPD or asthma were excluded. A probability score for prevalent SAO (FEV1/FVC<0.70) was developed via hierarchical group-lasso regularization from clinical variables in strata of sex and smoking status, and its discriminative accuracy for SAO was assessed in the pooled cohort as well as in an external validation cohort (NHANES 2011-12). Incident hospitalizations and deaths due to COPD (respiratory events) were defined by adjudication or administrative criteria in 4 of 9 cohorts. RESULTS Of 33,546 participants (mean age 52 years, 54% female, 44% non-Hispanic White), 4,424 (13.2%) had prevalent SAO. The incidence of respiratory events (Nat-risk=14,024) was 3-fold higher in participants with SAO versus those without (152 vs. 39 events/10,000 person-years). The probability score, which was based on six commonly available variables (age, sex, race/ethnicity, BMI, smoking status, smoking pack-years) was well-calibrated and showed excellent discrimination in both the testing sample (C-statistic 0.81, 95%CI 0.80-0.82) and in NHANES (C-statistic 0.83, 95%CI 0.80-0.86). Among participants with predicted probabilities ≥15%, 3.2 would need to undergo spirometry in order to detect one case of SAO. CONCLUSIONS Adults with SAO demonstrate excess respiratory hospitalization and mortality. A probability score for SAO using commonly available clinical risk factors may be suitable for targeting screening and primary prevention strategies.