Abstract Rationale The European Respiratory Society and American Thoracic Society (ERS/ATS) technical standard on pulmonary function test (PFT) interpretation states that a normal forced vital capacity (FVC) implies the absence of restriction. However, recent data suggest that restriction may be more common among patients with normal spirometry than previously reported, revealing the presence of a finding - restriction with normal spirometry - of unknown clinical significance. In this retrospective cohort study we sought to assess the clinical characteristics and outcomes associated with restriction with normal spirometry. Methods We interpreted PFTs with both static and dynamic lung volume measurements performed between 2012 and 2025 at four pulmonary diagnostic labs. Normal spirometry was present if both the FVC and the forced expiratory volume in 1 second to FVC (FEV1/FVC) z-scores were greater than or equal to -1.645, while restriction was present if the total lung capacity (TLC) z-score was less than -1.645. 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. Results We interpreted 83,886 PFTs from 47,597 patients (mean age 58.8 years, 59.8% women, 63.6% White). Restriction was present in 11,361 (25.7%) patients with normal spirometry, with a median TLC z-score of -2.2 (first quartile -2.6, third quartile -1.9). Among PFTs with normal spirometry, restriction was more likely in older patients (adjusted odds ratio aOR 1.01 per year, 95% CI 1.01-1.01), in non-White patients (aOR 1.33, 95% CI 1.26-1.41), and in patients with a diagnosis (aOR 3.65, 95% CI 3.43-3.88) or radiographic evidence (aOR 3.02, 95% CI 2.79-3.28) of interstitial lung disease (ILD). Restriction was less likely among women (aOR 0.64, 95% CI 0.60-0.67), patients with a diagnosis (0.74, 95% CI 0.67-0.82) or radiographic evidence (aOR 0.81, 95% CI 0.73-0.89) of chronic obstructive pulmonary disease, and patients with a greater residual volume (aOR 0.01 per standard deviation SD, 95% CI 0.01-0.01) or diffusing capacity for carbon monoxide (aOR 0.61 per SD, 95% CI 0.60-0.62). Restriction was associated with increased all-cause mortality (adjusted hazard ratio 1.45, 95% CI 1.34-1.57). Conclusions Restriction with normal spirometry is associated with ILD and with decreased survival. In this large, heterogenous cohort, clinically significant ventilatory impairments were present in more than 1 in 4 patients with normal spirometry. This abstract is funded by: NHLBI F32 HL167456
Moffett et al. (2026) studied this question.