Background: Preserved ratio impaired spirometry (PRISm, FEV1/FVC≥ 0.7 and FEV1 < 80% predicted),is regarded as a pre-COPD phenotype, and represents a potentially reversible state that may offer a critical window of opportunity for intervening against both COPD and lung cancer. However, the definition based solely on low FEV1 overlooks another significant pattern within the preserved-ratio category: restrictive spirometric pattern (RSP, FEV1/FVC≥ 0.7 and FVC < 80% predicted). While existing evidence suggests distinct mortality risk profiles between these two preserved-ratio phenotypes, no prospective study has comprehensively characterized their respective cancer risk spectra. This study therefore aims to clarify the distinct cancer risk profiles of PRISm, RSP, and their overlapping subgroup, which may offer new targets for intervention in lung and extra-pulmonary cancer prevention.
 
Methods: Participants were drawn from the UK Biobank and underwent baseline spirometry following standardized protocols, with the highest acceptable values of FEV1 and FVC being used. Percent-predicted FEV1 was derived from Global Lung Initiative (GLI) 2012 regression equations. Participants were categorized into six groups based on baseline lung function: (1) Normal spirometry; (2) PRISm only; (3) RSP only; (4) PRISm + RSP; (5) Mild COPD; (6) Moderate-severe COPD.The main endpoints were 20 site-specific cancers and the second were CVD and respiratory system disease (except lung cancer (LC)). Associations were evaluated using multivariable Cox proportional hazards models with adjustment for basic covariates and additional outcome-specific factors. Analyses used R version 4.3.1.
 
Results: Among 306,443 included participants (mean age 55.9 years; 46.0% men), the prevalence of spirometry patterns was: normal, 73.4%; RSP only, 1.0%; PRISm only, 3.1%; PRISm + RSP, 7.4%; mild COPD, 7.3%; and moderate-severe COPD, 7.9%. During a median follow-up of >13 years, 40,928 cancer cases (including 38,454 non-lung cancers), 23,158 CVD, and 71,163 respiratory disease cases were documented. Distinct preserved spirometric patterns demonstrated specific associations with cancer and common chronic diseases, including CVD and respiratory conditions. Compared with normal spirometry, PRISm only was significantly associated with an increased risk of LC (HR 1.53; 95% CI, 1.23-1.90) and respiratory diseases (HR 1.47; 95% CI, 1.42-1.51), but not with extra-pulmonary cancers. RSP only showed significant associations with increased risks of thyroid, gastric, renal, oral, and female breast cancers (HR 1.42-2.39) and CVD (HR 1.15; 95% CI, 1.02-1.29) while it showed no association with LC (HR 0.88; 95% CI, 0.50-1.56) and only a slight association with respiratory diseases (HR 1.07; 95% CI, 1.01-1.14). PRISm + RSP was linked to elevated risks of lung (HR 1.60; 95% CI, 1.38-1.86), oral, leukemia, renal, colorectal, and female breast cancers (HR 1.52-1.11). Additionally, this group had significantly higher risks of CVD (HR 1.28; 95% CI, 1.22-1.34), respiratory system diseases (HR 1.39; 95% CI, 1.36-1.42).

Conclusions: This study provides the first systematic evaluation of the cancer risk profiles associated with PRISm and RSP. We demonstrate that PRISm is specifically linked to LC, whereas RSP is associated with extra-pulmonary, obesity-related cancers but not LC. These distinct phenotypic associations are crucial for refining risk stratification and guiding targeted cancer prevention strategies in clinical and public health practice.

Conceptual Classification Chart of Spirometric Patterns.