03207nas a2200337 4500008004100000022001400041245013200055210006900187260001600256300001200272490000800284520218000292100002602472700002202498700002102520700002502541700002102566700001702587700002402604700001702628700002102645700002002666700002402686700002402710700002102734700002202755700002102777700001702798700001802815856003602833 2019 eng d a1535-497000aAlbuminuria, Lung Function Decline, and Risk of Incident Chronic Obstructive Pulmonary Disease. The NHLBI Pooled Cohorts Study.0 aAlbuminuria Lung Function Decline and Risk of Incident Chronic O c2019 Feb 01 a321-3320 v1993 a

RATIONALE: Chronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD.

OBJECTIVES: To test whether albuminuria was associated with lung function decline and incident CLRDs.

METHODS: Six U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications.

MEASUREMENTS AND MAIN RESULTS: Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P < 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease.

CONCLUSIONS: Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population-based sample.

1 aOelsner, Elizabeth, C1 aBalte, Pallavi, P1 aGrams, Morgan, E1 aCassano, Patricia, A1 aJacobs, David, R1 aBarr, Graham1 aBurkart, Kristin, M1 aKalhan, Ravi1 aKronmal, Richard1 aLoehr, Laura, R1 aO'Connor, George, T1 aSchwartz, Joseph, E1 aShlipak, Michael1 aTracy, Russell, P1 aTsai, Michael, Y1 aWhite, Wendy1 aYende, Sachin uhttps://chs-nhlbi.org/node/798004942nas a2200529 4500008004100000022001400041245009700055210006900152260001500221300001200236490000800248520351200256653001503768653001003783653000903793653002203802653001103824653002403835653001103859653001103870653000903881653000903890653001603899653002403915653003103939653001203970653001203982653001603994100002204010700002304032700002104055700001804076700002104094700001704115700002404132700002004156700002504176700002004201700002404221700002404245700002304269700002004292700002004312700001804332700002604350856003604376 2020 eng d a2168-611400aAssociation of Nonobstructive Chronic Bronchitis With Respiratory Health Outcomes in Adults.0 aAssociation of Nonobstructive Chronic Bronchitis With Respirator c2020 05 01 a676-6860 v1803 a

Importance: Chronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain.

Objective: To assess whether nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes in adult ever smokers and never smokers.

Design, Setting, and Participants: This prospective cohort study included 22 325 adults without initial airflow obstruction (defined as the ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity [FVC] of <0.70) or clinical asthma at baseline. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 9 US general population-based cohorts. Thus present study is based on data from 5 of these cohorts. Participants were enrolled from August 1971 through May 2007 and were followed up through December 2018.

Exposures: Nonobstructive chronic bronchitis was defined by questionnaire at baseline as both cough and phlegm for at least 3 months for at least 2 consecutive years.

Main Outcomes and Measures: Lung function was measured by prebronchodilator spirometry. Hospitalizations and deaths due to chronic lower respiratory disease and respiratory disease-related mortality were defined by events adjudication and administrative criteria. Models were stratified by smoking status and adjusted for anthropometric, sociodemographic, and smoking-related factors. The comparison group was participants without nonobstructive chronic bronchitis.

Results: Among 22 325 adults included in the analysis, mean (SD) age was 53.0 (16.3) years (range, 18.0-95.0 years), 58.2% were female, 65.9% were non-Hispanic white, and 49.6% were ever smokers. Among 11 082 ever smokers with 99 869 person-years of follow-up, participants with nonobstructive chronic bronchitis (300 [2.7%]) had accelerated decreases in FEV1 (4.1 mL/y; 95% CI, 2.1-6.1 mL/y) and FVC (4.7 mL/y; 95% CI, 2.2-7.2 mL/y), increased risks of chronic lower respiratory disease-related hospitalization or mortality (hazard ratio [HR], 2.2; 95% CI, 1.7-2.7), and greater respiratory disease-related (HR, 2.0; 95% CI, 1.1-3.8) and all-cause mortality (HR, 1.5; 95% CI, 1.3-1.8) compared with ever smokers without nonobstructive chronic bronchitis. Among 11 243 never smokers with 120 004 person-years of follow-up, participants with nonobstructive chronic bronchitis (151 [1.3%]) had greater rates of chronic lower respiratory disease-related hospitalization or mortality (HR, 3.1; 95% CI, 2.1-4.5) compared with never smokers without nonobstructive chronic bronchitis. Nonobstructive chronic bronchitis was not associated with FEV1:FVC decline or incident airflow obstruction. The presence of at least 1 of the component symptoms of nonobstructive chronic bronchitis (ie, chronic cough or phlegm), which was common in both ever smokers (11.0%) and never smokers (6.7%), was associated with adverse respiratory health outcomes.

Conclusions and Relevance: The findings suggest that nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes, particularly in ever smokers, and may be a high-risk phenotype suitable for risk stratification and targeted therapies.

10aAdolescent10aAdult10aAged10aAged, 80 and over10aAsthma10aBronchitis, Chronic10aFemale10aHumans10aLung10aMale10aMiddle Aged10aProspective Studies10aRespiratory Function Tests10aSmokers10aSmoking10aYoung Adult1 aBalte, Pallavi, P1 aChaves, Paulo, H M1 aCouper, David, J1 aEnright, Paul1 aJacobs, David, R1 aKalhan, Ravi1 aKronmal, Richard, A1 aLoehr, Laura, R1 aLondon, Stephanie, J1 aNewman, Anne, B1 aO'Connor, George, T1 aSchwartz, Joseph, E1 aSmith, Benjamin, M1 aSmith, Lewis, J1 aWhite, Wendy, B1 aYende, Sachin1 aOelsner, Elizabeth, C uhttps://chs-nhlbi.org/node/862005260nas 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