Prevalence, Risk Factors, and Clinical Implications of Preserved Ratio Impaired Spirometry: a UK Biobank Cohort Analysis

Background: Preserved ratio impaired spirometry (PRISm) is defined as a FEV of less than 80% predicted and a FEV/forced vital capacity (FVC) ratio of 0·70 or higher. Previous research has indicated that PRISm is associated with respiratory symptoms and is a precursor of chronic obstructive pulmonary disease (COPD). However, these findings are based on relatively small selective cohorts with short follow-up. We aimed to determine the prevalence, risk factors, clinical implications, and mortality of PRISm in a large adult general population.

Methods: For this cohort analysis, we used data from the UKBiobank to assess PRISm prevalence, risk factors and associated symptoms, and associated comorbidities in a large adult population. Participants with spirometry deemed acceptable by an investigator (best measure FEV and FVC values) at baseline were included. Participants were excluded if they did not have acceptable spirometry or were missing data on body-mass index or smoking status. Control spirometry was defined as a FEV of 80% or more predicted and a FEV/FVC ratio of 0·70 or higher. Airflow obstruction was defined as a FEV/FVC ratio of less than 0·70. We used multivariable regression to determine risk factors for PRISm and associated comorbidities. Individuals who lived within close proximity to an assessment centre were invited for follow-up, with repeat spirometry. Only participants who had been included at baseline were examined in follow-up. This allowed for a longitudinal analysis of PRISm over time and risk factors for transition to airflow obstruction. We also did the survival analysis for a 12-year period.

Findings: Participants were recruited by UK Biobank between Dec 19, 2006, and Oct 10, 2010. We included 351 874 UK Biobank participants (189 247 women and 162 627 men) in our study, with a median follow-up of 9·0 years (IQR 8·0-10·0). 38 639 (11·0%) of 351 874 participants had PRISm at baseline. After adjustment, PRISm was strongly associated with obesity (odds ratio [OR] 2·40 [2·26-2·55], p<0·0001), current smoking (1·48 [1·36-1·62], p<0·0001), and patient reported doctor-diagnosed asthma (1·76 [1·66-1·88], p<0·0001). Other risk factors identified included female sex, being overweight, trunk fat mass, and trunk fat percentage. PRISm was strongly associated with symptoms and comorbidity including increased risk of breathlessness (adjusted OR 2·0 [95% CI 1·91-2·14], p<0·0001) and cardiovascular disease (adjusted OR 1·71 [1·64-1·83], p<0·0001 for heart attack). Longitudinal analysis showed that 241 (12·2%) of 1973 participants who had PRISm at baseline had transitioned to airflow obstruction consistent with COPD. PRISm was associated with increased all-cause mortality (adjusted hazard ratio 1·61 [95% CI 1·53-1·69], p<0·0001) versus control participants.

Interpretation: PRISm was associated with breathlessness, multimorbidity, and increased risk of death, which does not seem to be explained by smoking, obesity, or existing lung disease. Although for many patients PRISm is transient, it is important to understand which individuals are at risk of progressive lung function abnormalities. Further research into the genetic, structural and functional pathophysiology of PRISm is warranted.

Funding: UK Medical Research Council and University of Bristol.