@article {6582, title = {Genome-wide association analysis identifies six new loci associated with forced vital capacity.}, journal = {Nat Genet}, volume = {46}, year = {2014}, month = {2014 Jul}, pages = {669-77}, abstract = {

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 {\texttimes} 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

}, keywords = {Cohort Studies, Databases, Genetic, Follow-Up Studies, Forced Expiratory Volume, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Lung Diseases, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Prognosis, Quantitative Trait Loci, Respiratory Function Tests, Spirometry, Vital Capacity}, issn = {1546-1718}, doi = {10.1038/ng.3011}, author = {Loth, Daan W and Soler Artigas, Maria and Gharib, Sina A and Wain, Louise V and Franceschini, Nora and Koch, Beate and Pottinger, Tess D and Smith, Albert Vernon and Duan, Qing and Oldmeadow, Chris and Lee, Mi Kyeong and Strachan, David P and James, Alan L and Huffman, Jennifer E and Vitart, Veronique and Ramasamy, Adaikalavan and Wareham, Nicholas J and Kaprio, Jaakko and Wang, Xin-Qun and Trochet, Holly and K{\"a}h{\"o}nen, Mika and Flexeder, Claudia and Albrecht, Eva and Lopez, Lorna M and de Jong, Kim and Thyagarajan, Bharat and Alves, Alexessander Couto and Enroth, Stefan and Omenaas, Ernst and Joshi, Peter K and Fall, Tove and Vi{\~n}uela, Ana and Launer, Lenore J and Loehr, Laura R and Fornage, Myriam and Li, Guo and Wilk, Jemma B and Tang, Wenbo and Manichaikul, Ani and Lahousse, Lies and Harris, Tamara B and North, Kari E and Rudnicka, Alicja R and Hui, Jennie and Gu, Xiangjun and Lumley, Thomas and Wright, Alan F and Hastie, Nicholas D and Campbell, Susan and Kumar, Rajesh and Pin, Isabelle and Scott, Robert A and Pietil{\"a}inen, Kirsi H and Surakka, Ida and Liu, Yongmei and Holliday, Elizabeth G and Schulz, Holger and Heinrich, Joachim and Davies, Gail and Vonk, Judith M and Wojczynski, Mary and Pouta, Anneli and Johansson, Asa and Wild, Sarah H and Ingelsson, Erik and Rivadeneira, Fernando and V{\"o}lzke, Henry and Hysi, Pirro G and Eiriksdottir, Gudny and Morrison, Alanna C and Rotter, Jerome I and Gao, Wei and Postma, Dirkje S and White, Wendy B and Rich, Stephen S and Hofman, Albert and Aspelund, Thor and Couper, David and Smith, Lewis J and Psaty, Bruce M and Lohman, Kurt and Burchard, Esteban G and Uitterlinden, Andr{\'e} G and Garcia, Melissa and Joubert, Bonnie R and McArdle, Wendy L and Musk, A Bill and Hansel, Nadia and Heckbert, Susan R and Zgaga, Lina and van Meurs, Joyce B J and Navarro, Pau and Rudan, Igor and Oh, Yeon-Mok and Redline, Susan and Jarvis, Deborah L and Zhao, Jing Hua and Rantanen, Taina and O{\textquoteright}Connor, George T and Ripatti, Samuli and Scott, Rodney J and Karrasch, Stefan and Grallert, Harald and Gaddis, Nathan C and Starr, John M and Wijmenga, Cisca and Minster, Ryan L and Lederer, David J and Pekkanen, Juha and Gyllensten, Ulf and Campbell, Harry and Morris, Andrew P and Gl{\"a}ser, Sven and Hammond, Christopher J and Burkart, Kristin M and Beilby, John and Kritchevsky, Stephen B and Gudnason, Vilmundur and Hancock, Dana B and Williams, O Dale and Polasek, Ozren and Zemunik, Tatijana and Kolcic, Ivana and Petrini, Marcy F and Wjst, Matthias and Kim, Woo Jin and Porteous, David J and Scotland, Generation and Smith, Blair H and Viljanen, Anne and Heli{\"o}vaara, Markku and Attia, John R and Sayers, Ian and Hampel, Regina and Gieger, Christian and Deary, Ian J and Boezen, H Marike and Newman, Anne and Jarvelin, Marjo-Riitta and Wilson, James F and Lind, Lars and Stricker, Bruno H and Teumer, Alexander and Spector, Timothy D and Mel{\'e}n, Erik and Peters, Marjolein J and Lange, Leslie A and Barr, R Graham and Bracke, Ken R and Verhamme, Fien M and Sung, Joohon and Hiemstra, Pieter S and Cassano, Patricia A and Sood, Akshay and Hayward, Caroline and Dupuis, Jos{\'e}e and Hall, Ian P and Brusselle, Guy G and Tobin, Martin D and London, Stephanie J} } @article {8042, title = {Harmonization of Respiratory Data From 9 US Population-Based Cohorts: The NHLBI Pooled Cohorts Study.}, journal = {Am J Epidemiol}, volume = {187}, year = {2018}, month = {2018 Nov 01}, pages = {2265-2278}, abstract = {

Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56\% were female; 49\% were never-smokers; and racial/ethnic composition was 44\% white, 22\% black, 28\% Hispanic/Latino, and 5\% American Indian. Over 96\% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13\%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5\% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.

}, issn = {1476-6256}, doi = {10.1093/aje/kwy139}, author = {Oelsner, Elizabeth C and Balte, Pallavi P and Cassano, Patricia A and Couper, David and Enright, Paul L and Folsom, Aaron R and Hankinson, John and Jacobs, David R and Kalhan, Ravi and Kaplan, Robert and Kronmal, Richard and Lange, Leslie and Loehr, Laura R and London, Stephanie J and Navas Acien, Ana and Newman, Anne B and O{\textquoteright}Connor, George T and Schwartz, Joseph E and Smith, Lewis J and Yeh, Fawn and Zhang, Yiyi and Moran, Andrew E and Mwasongwe, Stanford and White, Wendy B and Yende, Sachin and Barr, R Graham} } @article {7558, title = {Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.}, journal = {Nat Genet}, volume = {50}, year = {2018}, month = {2018 Jan}, pages = {42-53}, abstract = {

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

}, issn = {1546-1718}, doi = {10.1038/s41588-017-0014-7}, author = {Demenais, Florence and Margaritte-Jeannin, Patricia and Barnes, Kathleen C and Cookson, William O C and Altm{\"u}ller, Janine and Ang, Wei and Barr, R Graham and Beaty, Terri H and Becker, Allan B and Beilby, John and Bisgaard, Hans and Bjornsdottir, Unnur Steina and Bleecker, Eugene and B{\o}nnelykke, Klaus and Boomsma, Dorret I and Bouzigon, Emmanuelle and Brightling, Christopher E and Brossard, Myriam and Brusselle, Guy G and Burchard, Esteban and Burkart, Kristin M and Bush, Andrew and Chan-Yeung, Moira and Chung, Kian Fan and Couto Alves, Alexessander and Curtin, John A and Custovic, Adnan and Daley, Denise and de Jongste, Johan C and Del-Rio-Navarro, Blanca E and Donohue, Kathleen M and Duijts, Liesbeth and Eng, Celeste and Eriksson, Johan G and Farrall, Martin and Fedorova, Yuliya and Feenstra, Bjarke and Ferreira, Manuel A and Freidin, Maxim B and Gajdos, Zofia and Gauderman, Jim and Gehring, Ulrike and Geller, Frank and Genuneit, Jon and Gharib, Sina A and Gilliland, Frank and Granell, Raquel and Graves, Penelope E and Gudbjartsson, Daniel F and Haahtela, Tari and Heckbert, Susan R and Heederik, Dick and Heinrich, Joachim and Heli{\"o}vaara, Markku and Henderson, John and Himes, Blanca E and Hirose, Hiroshi and Hirschhorn, Joel N and Hofman, Albert and Holt, Patrick and Hottenga, Jouke and Hudson, Thomas J and Hui, Jennie and Imboden, Medea and Ivanov, Vladimir and Jaddoe, Vincent W V and James, Alan and Janson, Christer and Jarvelin, Marjo-Riitta and Jarvis, Deborah and Jones, Graham and Jonsdottir, Ingileif and Jousilahti, Pekka and Kabesch, Michael and K{\"a}h{\"o}nen, Mika and Kantor, David B and Karunas, Alexandra S and Khusnutdinova, Elza and Koppelman, Gerard H and Kozyrskyj, Anita L and Kreiner, Eskil and Kubo, Michiaki and Kumar, Rajesh and Kumar, Ashish and Kuokkanen, Mikko and Lahousse, Lies and Laitinen, Tarja and Laprise, Catherine and Lathrop, Mark and Lau, Susanne and Lee, Young-Ae and Lehtim{\"a}ki, Terho and Letort, S{\'e}bastien and Levin, Albert M and Li, Guo and Liang, Liming and Loehr, Laura R and London, Stephanie J and Loth, Daan W and Manichaikul, Ani and Marenholz, Ingo and Martinez, Fernando J and Matheson, Melanie C and Mathias, Rasika A and Matsumoto, Kenji and Mbarek, Hamdi and McArdle, Wendy L and Melbye, Mads and Mel{\'e}n, Erik and Meyers, Deborah and Michel, Sven and Mohamdi, Hamida and Musk, Arthur W and Myers, Rachel A and Nieuwenhuis, Maartje A E and Noguchi, Emiko and O{\textquoteright}Connor, George T and Ogorodova, Ludmila M and Palmer, Cameron D and Palotie, Aarno and Park, Julie E and Pennell, Craig E and Pershagen, G{\"o}ran and Polonikov, Alexey and Postma, Dirkje S and Probst-Hensch, Nicole and Puzyrev, Valery P and Raby, Benjamin A and Raitakari, Olli T and Ramasamy, Adaikalavan and Rich, Stephen S and Robertson, Colin F and Romieu, Isabelle and Salam, Muhammad T and Salomaa, Veikko and Schl{\"u}nssen, Vivi and Scott, Robert and Selivanova, Polina A and Sigsgaard, Torben and Simpson, Angela and Siroux, Val{\'e}rie and Smith, Lewis J and Solodilova, Maria and Standl, Marie and Stefansson, Kari and Strachan, David P and Stricker, Bruno H and Takahashi, Atsushi and Thompson, Philip J and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Tiesler, Carla M T and Torgerson, Dara G and Tsunoda, Tatsuhiko and Uitterlinden, Andr{\'e} G and van der Valk, Ralf J P and Vaysse, Amaury and Vedantam, Sailaja and von Berg, Andrea and von Mutius, Erika and Vonk, Judith M and Waage, Johannes and Wareham, Nick J and Weiss, Scott T and White, Wendy B and Wickman, Magnus and Widen, Elisabeth and Willemsen, Gonneke and Williams, L Keoki and Wouters, Inge M and Yang, James J and Zhao, Jing Hua and Moffatt, Miriam F and Ober, Carole and Nicolae, Dan L} } @article {8097, title = {Discriminative Accuracy of FEV1:FVC Thresholds for COPD-Related Hospitalization and Mortality.}, journal = {JAMA}, volume = {321}, year = {2019}, month = {2019 06 25}, pages = {2438-2447}, abstract = {

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.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Female, Forced Expiratory Volume, Hospitalization, Humans, Male, Middle Aged, Prognosis, Proportional Hazards Models, Pulmonary Disease, Chronic Obstructive, Risk Assessment, Vital Capacity}, issn = {1538-3598}, doi = {10.1001/jama.2019.7233}, author = {Bhatt, Surya P and Balte, Pallavi P and Schwartz, Joseph E and Cassano, Patricia A and Couper, David and Jacobs, David R and Kalhan, Ravi and O{\textquoteright}Connor, George T and Yende, Sachin and Sanders, Jason L and Umans, Jason G and Dransfield, Mark T and Chaves, Paulo H and White, Wendy B and Oelsner, Elizabeth C} } @article {8620, title = {Association of Nonobstructive Chronic Bronchitis With Respiratory Health Outcomes in Adults.}, journal = {JAMA Intern Med}, volume = {180}, year = {2020}, month = {2020 05 01}, pages = {676-686}, abstract = {

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.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Asthma, Bronchitis, Chronic, Female, Humans, Lung, Male, Middle Aged, Prospective Studies, Respiratory Function Tests, Smokers, Smoking, Young Adult}, issn = {2168-6114}, doi = {10.1001/jamainternmed.2020.0104}, author = {Balte, Pallavi P and Chaves, Paulo H M and Couper, David J and Enright, Paul and Jacobs, David R and Kalhan, Ravi and Kronmal, Richard A and Loehr, Laura R and London, Stephanie J and Newman, Anne B and O{\textquoteright}Connor, George T and Schwartz, Joseph E and Smith, Benjamin M and Smith, Lewis J and White, Wendy B and Yende, Sachin and Oelsner, Elizabeth C} } @article {8623, title = {A Dyadic Growth Modeling Approach for Examining Associations Between Weight Gain and Lung Function Decline.}, journal = {Am J Epidemiol}, volume = {189}, year = {2020}, month = {2020 10 01}, pages = {1173-1184}, abstract = {

The relationship between body weight and lung function is complex. Using a dyadic multilevel linear modeling approach, treating body mass index (BMI; weight (kg)/height (m)2) and lung function as paired, within-person outcomes, we tested the hypothesis that persons with more rapid increase in BMI exhibit more rapid decline in lung function, as measured by forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio (FEV1:FVC). Models included random intercepts and slopes and adjusted for sociodemographic and smoking-related factors. A sample of 9,115 adults with paired measurements of BMI and lung function taken at >=3 visits were selected from a pooled set of 5 US population-based cohort studies (1983-2018; mean age at baseline = 46 years; median follow-up, 19 years). At age 46 years, average annual rates of change in BMI, FEV1, FVC, and FEV1:FVC ratio were 0.22 kg/m2/year, -25.50 mL/year, -21.99 mL/year, and~-0.24\%/year, respectively. Persons with steeper BMI increases had faster declines in FEV1 (r~=~-0.16) and FVC (r~=~-0.26) and slower declines in FEV1:FVC ratio (r~=~0.11) (all P~values <~0.0001). Results were similar in subgroup analyses. Residual correlations were negative (P~<~0.0001), suggesting additional interdependence between BMI and lung function. Results show that greater rates of weight gain are associated with greater rates of lung function loss.

}, keywords = {Adult, Aged, Body Mass Index, Cohort Studies, Humans, Linear Models, Lung, Middle Aged, Respiratory Function Tests, Weight Gain}, issn = {1476-6256}, doi = {10.1093/aje/kwaa059}, author = {Cornelius, Talea and Schwartz, Joseph E and Balte, Pallavi and Bhatt, Surya P and Cassano, Patricia A and Currow, David and Jacobs, David R and Johnson, Miriam and Kalhan, Ravi and Kronmal, Richard and Loehr, Laura and O{\textquoteright}Connor, George T and Smith, Benjamin and White, Wendy B and Yende, Sachin and Oelsner, Elizabeth C} } @article {8402, title = {Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study.}, journal = {Lancet Respir Med}, volume = {8}, year = {2020}, month = {2020 01}, pages = {34-44}, abstract = {

BACKGROUND: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease.

METHODS: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (>=17 years), two recruited middle-aged and older adults (>=45 years), and two recruited only elderly adults (>=65 years) with examinations done between 1983 and 2014. FEV decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption.

FINDINGS: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV decline at the median age (57 years) was 31{\textperiodcentered}01 mL per year (95\% CI 30{\textperiodcentered}66-31{\textperiodcentered}37) in sustained never-smokers, 34{\textperiodcentered}97 mL per year (34{\textperiodcentered}36-35{\textperiodcentered}57) in former smokers, and 39{\textperiodcentered}92 mL per year (38{\textperiodcentered}92-40{\textperiodcentered}92) in current smokers. With adjustment, former smokers showed an accelerated FEV decline of 1{\textperiodcentered}82 mL per year (95\% CI 1{\textperiodcentered}24-2{\textperiodcentered}40) compared to never-smokers, which was approximately 20\% of the effect estimate for current smokers (9{\textperiodcentered}21 mL per year; 95\% CI 8{\textperiodcentered}35-10{\textperiodcentered}08). Compared to never-smokers, accelerated FEV decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV decline in current smokers consuming less than five cigarettes per day (7{\textperiodcentered}65 mL per year; 95\% CI 6{\textperiodcentered}21-9{\textperiodcentered}09) was 68\% of that in current smokers consuming 30 or more cigarettes per day (11{\textperiodcentered}24 mL per year; 9{\textperiodcentered}86-12{\textperiodcentered}62), and around five times greater than in former smokers (1{\textperiodcentered}57 mL per year; 1{\textperiodcentered}00-2{\textperiodcentered}14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results.

INTERPRETATION: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage.

FUNDING: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.

}, keywords = {Adult, Aged, Case-Control Studies, Ex-Smokers, Female, Follow-Up Studies, Humans, Lung, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Non-Smokers, Respiratory Physiological Phenomena, Smokers, Smoking, Spirometry, United States, Young Adult}, issn = {2213-2619}, doi = {10.1016/S2213-2600(19)30276-0}, author = {Oelsner, Elizabeth C and Balte, Pallavi P and Bhatt, Surya P and Cassano, Patricia A and Couper, David and Folsom, Aaron R and Freedman, Neal D and Jacobs, David R and Kalhan, Ravi and Mathew, Amanda R and Kronmal, Richard A and Loehr, Laura R and London, Stephanie J and Newman, Anne B and O{\textquoteright}Connor, George T and Schwartz, Joseph E and Smith, Lewis J and White, Wendy B and Yende, Sachin} } @article {9156, title = {Pooled Cohort Probability Score for Subclinical Airflow Obstruction.}, journal = {Ann Am Thorac Soc}, volume = {19}, year = {2022}, month = {2022 08}, pages = {1294-1304}, abstract = {

Early detection of chronic obstructive pulmonary disease (COPD) is a public health priority. Airflow obstruction is the single most important risk factor for adverse COPD outcomes, but spirometry is not routinely recommended for screening. To describe the burden of subclinical airflow obstruction (SAO) and to develop a probability score for SAO to inform potential detection and prevention programs. Lung function and clinical data were harmonized and pooled across nine U.S. general population cohorts. Adults with respiratory symptoms, inhaler use, or prior diagnosis of COPD or asthma were excluded. A probability score for prevalent SAO (forced expiratory volume in 1 second/forced vital capacity < 0.70) was developed via hierarchical group-lasso regularization from clinical variables in strata of sex and smoking status, and its discriminative accuracy for SAO was assessed in the pooled cohort as well as in an external validation cohort (NHANES [National Health and Nutrition Examination Survey] 2011-2012). Incident hospitalizations and deaths due to COPD (respiratory events) were defined by adjudication or administrative criteria in four of nine cohorts. Of 33,546 participants (mean age 52 yr, 54\% female, 44\% non-Hispanic White), 4,424 (13.2\%) had prevalent SAO. The incidence of respiratory events ( = 14,024) was threefold higher in participants with SAO versus those without (152 vs. 39 events/10,000 person-years). The probability score, which was based on six commonly available variables (age, sex, race and/or ethnicity, body mass index, smoking status, and smoking pack-years) was well calibrated and showed excellent discrimination in both the testing sample (C-statistic, 0.81; 95\% confidence interval [CI], 0.80-0.82) and in NHANES (C-statistic, 0.83; 95\% CI, 0.80-0.86). Among participants with predicted probabilities ⩾ 15\%, 3.2 would need to undergo spirometry to detect one case of SAO. Adults with SAO demonstrate excess respiratory hospitalization and mortality. A probability score for SAO using commonly available clinical risk factors may be suitable for targeting screening and primary prevention strategies.

}, keywords = {Adult, Female, Forced Expiratory Volume, Humans, Lung, Male, Middle Aged, Nutrition Surveys, Pulmonary Disease, Chronic Obstructive, Risk Factors, Spirometry, Vital Capacity}, issn = {2325-6621}, doi = {10.1513/AnnalsATS.202109-1020OC}, author = {Bhatt, Surya P and Balte, Pallavi P and Schwartz, Joseph E and Jaeger, Byron C and Cassano, Patricia A and Chaves, Paulo H and Couper, David and Jacobs, David R and Kalhan, Ravi and Kaplan, Robert and Lloyd-Jones, Donald and Newman, Anne B and O{\textquoteright}Connor, George and Sanders, Jason L and Smith, Benjamin M and Sun, Yifei and Umans, Jason G and White, Wendy B and Yende, Sachin and Oelsner, Elizabeth C} } @article {9980, title = {Associations of metabolic syndrome with lung function decline and clinical respiratory outcomes: the NHLBI Pooled Cohort Study.}, journal = {ERJ Open Res}, volume = {11}, year = {2025}, month = {2025 Jul}, abstract = {

BACKGROUND: Whether metabolic syndrome (MetS) increases the risk of chronic lung diseases remains uncertain. We aimed to test whether MetS was associated with lung function and clinical respiratory outcomes.

METHODS: Data were harmonised from six US general population-based prospective cohorts. Participants with baseline airflow limitation (forced expiratory volume in 1 s (FEV):forced vital capacity (FVC) <0.70), restriction (FEV:FVC >=0.7, FVC <80\%), clinical chronic lower respiratory disease (CLRD) or cardiovascular disease were excluded. MetS was defined at baseline as the presence of at least three of the following: central obesity, high triglycerides, low high-density lipoprotein cholesterol, high blood pressure (BP) and high fasting glucose. Associations with lung function decline and incident clinical respiratory events were tested in linear mixed models and Cox models, respectively, adjusted for sociodemographic, anthropometric, smoking and clinical factors. The five subcomponents of MetS were evaluated separately in secondary analyses.

RESULTS: Of 15 728 participants (mean age 49.6 years, 57.6\% female, 68.6\% White, 27.0\% Black), 4422 (28.1\%) had MetS. In fully adjusted models that included body weight, MetS was associated with greater rate of FVC decline (-0.89 mL{\textperiodcentered}year, 95\% CI -1.73- -0.05) and incident restriction (1085 cases, hazard ratio 1.52, 95\% CI 1.30-1.77), but not FEV decline, incident airflow limitation or clinical respiratory outcomes. Among the subcomponents of MetS, central obesity, high BP and high fasting glucose were associated with incident restriction, while high BP alone was associated with incident airflow limitation, CLRD-related events and respiratory-related mortality.

CONCLUSIONS: MetS was associated with accelerated FVC decline and incident restriction, but not incident obstruction, in healthy adults.

}, issn = {2312-0541}, doi = {10.1183/23120541.01337-2024}, author = {Choi, Yuni and Balte, Pallavi P and Jacobs, David R and London, Stephanie J and Navas-Acien, Ana and Newman, Anne B and O{\textquoteright}Connor, George T and Schwartz, Joseph E and Smith, Benjamin M and White, Wendy B and Yende, Sachin and Oelsner, Elizabeth C} } @article {9902, title = {Low Lung Function Is Associated with High Population Attributable Fraction for Cardiovascular Mortality.}, journal = {Ann Am Thorac Soc}, volume = {22}, year = {2025}, month = {2025 Mar}, pages = {359-366}, abstract = {

Chronic lung diseases are associated with increased risk of mortality due to coronary heart disease (CHD). Nonetheless, the population attributable fraction (PAF) of lung function impairment relative to other established cardiovascular risk factors is unclear. To evaluate the PAF of low lung function for CHD mortality We harmonized and pooled lung function and clinical data across eight U.S. general population cohorts. Impaired lung function was defined as forced expiratory volume in 1 second (FEV) and/or forced vital capacity <= 95\% predicted on baseline spirometry. The association between CHD mortality and risk factors was assessed using cause-specific proportional hazards and Fine-Gray proportional subdistribution hazard models, treating non-CHD mortality as a competing risk. Models were adjusted for lung function as well as age, sex, race/ethnicity, educational attainment, body mass index, smoking status, pack-years of smoking, diabetes mellitus, high-density lipoprotein, and high low-density lipoprotein (>=130 mg/dl). PAF was calculated as the relative change in the average absolute risk of 10-year CHD mortality by elimination of lung function lower than 95\% predicted. Among 35,143 participants, 1,844 of 13,174 (14.0\%) deaths were due to CHD. Compared with percentage predicted FEV (FEVpp) > 95\%, the subdistribution adjusted hazard ratio for low FEVpp was 1.30 (95\% confidence interval, 1.18-1.44). The PAF for FEVpp <= 95\% was 12\%, ranking low FEV third on the list of PAF for CHD mortality, after hypertension and diabetes. Low FEVpp ranked second in the subgroup of active smokers (PAF 14\%), after hypertension. Low lung function, even in the range considered clinically normal, ranks high on the list of attributable risk factors for CHD mortality and should be considered in cardiovascular risk stratification.

}, keywords = {Adult, Aged, Coronary Disease, Female, Forced Expiratory Volume, Humans, Lung, Lung Diseases, Male, Middle Aged, Proportional Hazards Models, Risk Factors, Smoking, Spirometry, United States, Vital Capacity}, issn = {2325-6621}, doi = {10.1513/AnnalsATS.202407-715OC}, author = {Bhatt, Surya P and Wu, Chaoqi and Sun, Yifei and Balte, Pallavi P and Schwartz, Joseph E and Divo, Miguel J and Jaeger, Byron C and Chaves, Paulo H and Couper, David and Jacobs, David R and Lloyd-Jones, Donald and Kalhan, Ravi and Newman, Anne B and O{\textquoteright}Connor, George T and Umans, Jason G and White, Wendy B and Yende, Sachin and Oelsner, Elizabeth C} }