Abstract
Importance: Chronic lung diseases are a leading cause of morbidity and mortality. Unlike chronic obstructive pulmonary disease, clinical outcomes associated with proportional reductions in expiratory lung volumes without obstruction, otherwise known as preserved ratio impaired spirometry (PRISm), are poorly understood. Objective: To examine the prevalence, correlates, and clinical outcomes associated with PRISm in US adults. Design, Setting, and Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study was a retrospective study with harmonized pooled data from 9 US general population-based cohorts (enrollment, 65251 participants aged 18 to 102 years of whom 53701 participants had valid baseline lung function) conducted from 1971-2011 (final follow-up, December 2018). Exposures: Participants were categorized into mutually exclusive groups by baseline lung function. PRISm was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1:FVC) greater than or equal to 0.70 and FEV1less than 80% predicted; obstructive spirometry FEV1:FVC ratio of less than 0.70; and normal spirometry FEV1:FVC ratio greater than or equal to 0.7 and FEV1greater than or equal to 80% predicted. Main Outcomes and Measures: Main outcomes were all-cause mortality, respiratory-related mortality, coronary heart disease (CHD)-related mortality, respiratory-related events (hospitalizations and mortality), and CHD-related events (hospitalizations and mortality) classified by adjudication or validated administrative criteria. Absolute risks were adjusted for age and smoking status. Poisson and Cox proportional hazards models comparing PRISm vs normal spirometry were adjusted for age, sex, race and ethnicity, education, body mass index, smoking status, cohort, and comorbidities. Results: Among all participants (mean [SD] age, 53.2 [15.8] years, 56.4% women, 48.5% never-smokers), 4582 (8.5%) had PRISm. The presence of PRISm relative to normal spirometry was significantly associated with obesity (prevalence, 48.3% vs 31.4%; prevalence ratio [PR], 1.68 [95% CI, 1.55-1.82]), underweight (prevalence, 1.4% vs 1.0%; PR, 2.20 [95% CI, 1.72-2.82]), female sex (prevalence, 60.3% vs 59.0%; PR, 1.07 [95% CI, 1.01-1.13]), and current smoking (prevalence, 25.2% vs 17.5%; PR, 1.33 [95% CI, 1.22-1.45]). PRISm, compared with normal spirometry, was significantly associated with greater all-cause mortality (29.6/1000 person-years vs 18.0/1000 person-years; difference, 11.6/1000 person-years [95% CI, 10.0-13.1]; adjusted hazard ratio [HR], 1.50 [95% CI, 1.42-1.59]), respiratory-related mortality (2.1/1000 person-years vs 1.0/1000 person-years; difference, 1.1/1000 person-years [95% CI, 0.7-1.6]; adjusted HR, 1.95 [95% CI, 1.54-2.48]), CHD-related mortality (5.4/1000 person-years vs 2.6/1000 person-years; difference, 2.7/1000 person-years [95% CI, 2.1-3.4]; adjusted HR, 1.55 [95% CI, 1.36-1.77]), respiratory-related events (12.2/1000 person-years vs 6.0/1000 person-years; difference, 6.2/1000 person-years [95% CI, 4.9-7.5]; adjusted HR, 1.90 [95% CI, 1.69-2.14]), and CHD-related events (11.7/1000 person-years vs 7.0/1000 person-years; difference, 4.7/1000 person-years [95% CI, 3.7-5.8]; adjusted HR, 1.30 [95% CI, 1.18-1.42]). Conclusions and Relevance: In a large, population-based sample of US adults, baseline PRISm, compared with normal spirometry, was associated with a small but statistically significant increased risk for mortality and adverse cardiovascular and respiratory outcomes. Further research is needed to explore whether this association is causal..
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2287-2298 |
| Number of pages | 12 |
| Journal | JAMA |
| Volume | 326 |
| Issue number | 22 |
| DOIs | |
| State | Published - Dec 14 2021 |
Funding
receipt of personal fees for serving as faculty and expert content provider for chronic obstructive pulmonary disease (COPD) continuing medical education for PriMed. Dr Balte reported funding from the National Institutes of Health (NIH). Dr Bhatt reported grants from NIH; personal fees from Sanofi (consulting), Boehringer Ingelheim (consulting), GlaxoSmithKline (advisory board), and Sunovion (advisory board) outside the submitted work. Dr Couper reported grants from the National Heart, Lunb, and Blood Institute (NHLBI) and from the COPD Foundation during the conduct of the study. Dr Daviglus reported grants from NIH during the conduct of the study. Dr Dransfield reported grants from NIH during the conduct of the study; personal fees from AstraZeneca, GlaxoSmithKline, Mereo, Quark, and Teva (consulting fees); personal fees for travel from Pulmonx; contracted clinical trial support from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Gala, GlaxoSmithKline, Nuvaira, PneumRx/BTG, and Pulmonx; and grants from NIH, the US Department of Defense, and the American Lung Association outside the submitted work. Dr Kalhan reported grants from NHLBI during the conduct of the study; grants and personal fees from Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline; personal fees from CVS Caremark, Aptus Health, Boston Scientific, and the Boston Consulting Group; and grants from PneumRx (BTG) and Spiration outside the submitted work. Dr Navas-Acien reported grants from NIH during the conduct of the study and grants from NIH outside the submitted work. Dr O'Connor reported grants from NIH during the conduct of the study. Dr Sanders reported other from Vertex Pharmaceuticals (employment at the time of publication). Dr Smith reported grants from NIH (R01-HL130506) during the conduct of the study; and grants from Canadian Institutes of Health Research outside the submitted work. Dr Oelsner reported grants from NHLBI during the conduct of the study. No other disclosures were reported. cohorts: NIH/NHLBI (R21-HL121457, R21-HL129924, K23-HL130627), US Department of Veterans Affairs Rehabilitation Research and Development Award (IK2 RX002165 to Dr Wan) and NIH grants (R01HL151421, R21EB027891, and K23HL133438 to Dr Bhatt). To the Atherosclerosis Risk in Communities study (ARIC), which has been funded in whole or in part with funds from NHLBI, NIH, and the US Department of Health and Human Services (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I); and Dr London is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS). To the Coronary Artery Risk Development in Young Adults Study (CARDIA): support is provided and conducted by the NHLBI in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I); and a grant to Dr Kalhan (R01 HL122477). To the Cardiovascular Health Study (CHS): research was supported by NHLBI with an additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS) (contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, 75N92021D00006; and grants U01HL080295 and U01HL130114), and the National Institute on Aging (NIA) (R01AG023629). To the Framingham Offspring Cohort (FOC): support was provided by the Framingham Heart Study of the NHLBI/NIH and Boston University School of Medicine and funded in whole or in part with from the NHLBI/NIH Department of Health and Human Services (contracts 75N92019D00031 and HHSN268201500001I). To Health ABC: support was provided by the NIA (contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; NIA grant R01-AG028050; and NINR grant R01-NR012459) and funded in part by the Intramural Research Program of the NIH/NIA. To the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): contract support was provided from the NHLBI to the University of North Carolina (HHSN268201300001I, N01-HC-65233), University of Miami (HHSN268201300004I, N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I, N01-HC-65235), University of Illinois at Chicago (HHSN268201300003I, N01-HC-65236 to Northwestern University), and San Diego State University (HHSN268201300005I, N01-HC-65237). The following institutes, centers, or offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities (NIMHD), National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution\u2014Office of Dietary Supplements. To the Jackson Heart Study (JHS): support was provided and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I, HHSN26800001), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from NHLBI and NIMHD. To the Multi-Ethnic Study of Atherosclerosis (MESA) lung study was funded by grants from the NIH/NHLBI (R01-1 HL130506, R01-HL077612, R01-HL093081, and R01-HL121270), contracts from NHLBI (75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169), and by grants from the National Center for Advancing Translational Sciences (UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420. This article was developed under the Science to Achieve Results research assistance agreements (RD831697 [MESA Air] and RD-83830001 [MESA Air Next Stage]) awarded by the US Environmental Protection Agency. To the Strong Heart Study (SHS): support was provided in whole or in part with federal funds from NHLBI/NIH, Department of Health and Human Services (contracts 75N92019D00027, 75N92019D00028, 75N92019D00029, and 75N92019D00030) and by NIEHS (R01ES032638). The study was previously supported by research grants from NHLBI (R01HL109315, R01HL109301, R01HL109284, R01HL109282, R01HL109319, R01HL090863), NIEHS (R01ES025216 and R01ES021367) and by cooperative agreements from NIH (U01HL41642, U01HL41652, U01HL41654, U01HL65520, and U01HL65521).
ASJC Scopus subject areas
- General Medicine
