Spirometry restriction linked to higher interstitial lung disease and mortality risk in a large cohort.

Background Though the European Respiratory Society and American Thoracic Society technical standard on pulmonary function test interpretation recommends the use of a normal forced vital capacity (FVC) to infer the absence of restriction, recent data suggest that restriction may be present in as many as one in five patients with normal spirometry. The clinical implications of restriction with normal spirometry are unknown. Methods We interpreted pulmonary function tests (PFTs) with both static and dynamic lung volume measurements performed between 2012 and 2025 at four pulmonary diagnostic labs. We used multivariable logistic regression to identify clinical characteristics associated with restriction among patients with normal spirometry and used a Cox proportional hazards model to assess the association of restriction with survival, adjusting for age, height, sex, forced expiratory volume in 1 second (FEV#sub[1]) z-score, FVC z-score, and FEV#sub[1]/FVC z-score. Results We interpreted 83,886 PFTs from 47,597 patients (mean age 58.8 years, 59.8% female, 63.6% White). Normal spirometry was present in 44,246 (52.7%) PFTs. Restriction was present in 11,361 (25.7%) PFTs with normal spirometry. Among patients with normal spirometry, restriction was associated with interstitial lung disease (adjusted odds ratio 3.40, 95% confidence interval [CI] 3.20--3.60) and with increased all-cause mortality (adjusted hazard ratio 1.45, 95% CI 1.34--1.57). Interpretation Restriction with normal spirometry is associated with interstitial lung disease and with increased mortality. Normal spirometry performs poorly as a screening test to exclude clinically significant ventilatory impairments.