04467nas a2200481 4500008004100000022001400041245009900055210006900154260001500223300001400238490000800252520309300260653000903353653002203362653001903384653001103403653002903414653002003443653001103463653000903474653001603483653001403499653003203513653004303545653002003588653001903608100002003627700002203647700002403669700002503693700001803718700002103736700001703757700002403774700001803798700002203816700002003838700002403858700002103882700002003903700002603923856003603949 2019 eng d a1538-359800aDiscriminative Accuracy of FEV1:FVC Thresholds for COPD-Related Hospitalization and Mortality.0 aDiscriminative Accuracy of FEV1FVC Thresholds for COPDRelated Ho c2019 06 25 a2438-24470 v3213 a

Importance: According to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial.

Objective: To determine the discriminative accuracy of various FEV1:FVC fixed thresholds for predicting COPD-related hospitalization and mortality.

Design, Setting, and Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population-based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016.

Exposures: Presence of airflow obstruction, which was defined by a baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN).

Main Outcomes and Measures: The primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV1:FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach.

Results: Among 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, -0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models.

Conclusions and Relevance: Defining airflow obstruction as FEV1:FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD.

10aAged10aAged, 80 and over10aCohort Studies10aFemale10aForced Expiratory Volume10aHospitalization10aHumans10aMale10aMiddle Aged10aPrognosis10aProportional Hazards Models10aPulmonary Disease, Chronic Obstructive10aRisk Assessment10aVital Capacity1 aBhatt, Surya, P1 aBalte, Pallavi, P1 aSchwartz, Joseph, E1 aCassano, Patricia, A1 aCouper, David1 aJacobs, David, R1 aKalhan, Ravi1 aO'Connor, George, T1 aYende, Sachin1 aSanders, Jason, L1 aUmans, Jason, G1 aDransfield, Mark, T1 aChaves, Paulo, H1 aWhite, Wendy, B1 aOelsner, Elizabeth, C uhttps://chs-nhlbi.org/node/809705260nas a2200553 4500008004100000022001400041245009600055210006900151260001500220300001400235490000800249520374200257653001003999653000904009653002204018653002804040653001104068653002904079653001104108653000904119653001804128653000904146653001604155653001504171653002604186653001504212653001804227653001904245100001804264700001904282700002404301700002004325700002504345700001804370700002404388700002404412700002004436700002104456700001704477700002504494700002104519700002404540700002204564700002304586700001704609700001804626700002604644856003604670 2021 eng d a1538-359800aAssociation Between Preserved Ratio Impaired Spirometry and Clinical Outcomes in US Adults.0 aAssociation Between Preserved Ratio Impaired Spirometry and Clin c2021 12 14 a2287-22980 v3263 a

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, 65 251 participants aged 18 to 102 years of whom 53 701 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 FEV1 less 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 FEV1 greater 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.

10aAdult10aAged10aAged, 80 and over10aCardiovascular Diseases10aFemale10aForced Expiratory Volume10aHumans10aLung10aLung Diseases10aMale10aMiddle Aged10aPrevalence10aRetrospective Studies10aSpirometry10aUnited States10aVital Capacity1 aWan, Emily, S1 aBalte, Pallavi1 aSchwartz, Joseph, E1 aBhatt, Surya, P1 aCassano, Patricia, A1 aCouper, David1 aDaviglus, Martha, L1 aDransfield, Mark, T1 aGharib, Sina, A1 aJacobs, David, R1 aKalhan, Ravi1 aLondon, Stephanie, J1 aNavas-Acien, Ana1 aO'Connor, George, T1 aSanders, Jason, L1 aSmith, Benjamin, M1 aWhite, Wendy1 aYende, Sachin1 aOelsner, Elizabeth, C uhttps://chs-nhlbi.org/node/9114