@article {721, title = {Hormone replacement therapy and sleep-disordered breathing.}, journal = {Am J Respir Crit Care Med}, volume = {167}, year = {2003}, month = {2003 May 01}, pages = {1186-92}, abstract = {

Disordered breathing during sleep is more common among postmenopausal women than among their premenopausal counterparts, possibly because of declining levels of estrogen and progesterone. We examined the relationship between the use of replacement hormones and sleep-disordered breathing in a sample of 2,852 noninstitutionalized women, 50 years of age or older, who participated in the Sleep Heart Health Study. The frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index) was determined by unattended, single-night polysomnography at the participant{\textquoteright}s home. The prevalence of sleep-disordered breathing (apnea-hypopnea index of 15 or more) among hormone users (61 of 907) was approximately half the prevalence among nonusers (286 of 1,945). Multivariable adjustment for known determinants of the disorder, including age, body mass index, and neck circumference, has attenuated the association, but only moderately (adjusted odds ratio, 0.55; 95\% confidence interval, 0.41 to 0.75). The inverse association between hormone use and sleep-disordered breathing was evident in various subgroups and was particularly strong among women 50 to 59 years old (adjusted odds ratio, 0.36; 95\% confidence interval, 0.21 to 0.60). If the observed associations are causal, hormone replacement therapy could have a role in preventing or alleviating sleep-disordered breathing.

}, keywords = {Age Distribution, Aged, Body Mass Index, Causality, Cohort Studies, Confidence Intervals, Estrogen Replacement Therapy, Female, Humans, Logistic Models, Middle Aged, Multivariate Analysis, Odds Ratio, Polysomnography, Postmenopause, Prevalence, Sensitivity and Specificity, Severity of Illness Index, Sleep Apnea Syndromes, Sleep Stages, United States}, issn = {1073-449X}, doi = {10.1164/rccm.200210-1238OC}, author = {Shahar, Eyal and Redline, Susan and Young, Terry and Boland, Lori L and Baldwin, Carol M and Nieto, F Javier and O{\textquoteright}Connor, George T and Rapoport, David M and Robbins, John A} } @article {715, title = {Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease.}, journal = {Am J Respir Crit Care Med}, volume = {167}, year = {2003}, month = {2003 Jan 01}, pages = {7-14}, abstract = {

Neither the association between obstructive airways disease (OAD) and sleep apnea-hypopnea (SAH) nor the sleep consequences of each disorder alone and together have been characterized in an adult community setting. Our primary aims were (1) to determine if there is an association between OAD and SAH and (2) identify predictors of oxyhemoglobin desaturation during sleep in persons having OAD with and without SAH. Polysomnography and spirometry results from 5,954 participants in the Sleep Heart Health Study were analyzed. OAD was defined by a FEV1/FVC value less than 70\%. Assessment of SAH prevalence in OAD was performed using thresholds of respiratory disturbance index (RDI) greater than 10 and greater than 15. A total of 1,132 participants had OAD that was predominantly mild (FEV1/FVC 63.81 +/- 6.56\%, mean +/- SD). SAH was not more prevalent in participants with OAD than in those without OAD (22.32 versus 28.86\%, with and without OAD, respectively, at RDI threshold values greater than 10; and 13.97 versus 18.63\%, with and without OAD, respectively, at RDI threshold value greater than 15). In the absence of SAH, the adjusted odds ratio for sleep desaturation (> 5\% total sleep time with saturation < 90\%) was greater than 1.9 when FEV1/FVC was less than 65\%. Participants with both OAD and SAH had greater sleep perturbation and desaturation than those with one disorder. Generally mild OAD alone was associated with minimally altered sleep quality. We conclude that (1) there is no association between generally mild OAD and SAH; (2) exclusive of SAH and after adjusting for demographic factors and awake oxyhemoglobin saturation, an FEV1/FVC value less than 65\% is associated with increased risk of sleep desaturation; (3) desaturation is greater in persons with both OAD and SAH compared with each of these alone; and (4) individuals with generally mild OAD and without SAH in the community have minimally perturbed sleep.

}, keywords = {Aged, Cohort Studies, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Oxyhemoglobins, Polysomnography, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Sleep, Sleep Apnea, Obstructive, Spirometry, Vital Capacity}, issn = {1073-449X}, doi = {10.1164/rccm.2203046}, author = {Sanders, Mark H and Newman, Anne B and Haggerty, Catherine L and Redline, Susan and Lebowitz, Michael and Samet, Jonathan and O{\textquoteright}Connor, George T and Punjabi, Naresh M and Shahar, Eyal} } @article {839, title = {Predictors of heartburn during sleep in a large prospective cohort study.}, journal = {Chest}, volume = {127}, year = {2005}, month = {2005 May}, pages = {1658-66}, abstract = {

BACKGROUND AND AIMS: Nocturnal gastroesophageal reflux, which may result in nocturnal heartburn, has been demonstrated to be associated with a more severe form of gastroesophageal reflux disease (GERD). The aim of this study was to determine the clinical predictors of heartburn during sleep in a large prospective cohort study.

METHODS: Study subjects were members of the parent cohorts from which the Sleep Heart Health Study (SHHS) recruited participants. SHHS is a multicenter, longitudinal, cohort study of the cardiovascular consequences of sleep-disordered breathing. As part of the recruitment process, parent cohort members completed a questionnaire that permitted an assessment of the relationships between heartburn during sleep, and patient demographics, sleep abnormalities, medical history, and social habits in nine community-based parent cohorts across the United States. All variables, significant at the p < 0.05 level, were included as independent variables in multivariate logistic regression models with heartburn during sleep status included as the dependent variable

RESULTS: A total of 15,314 subjects completed the questions about heartburn during sleep, and of these, 3,806 subjects (24.9\%) reported having this symptom. In four increasingly comprehensive multivariate models, increased body mass index (BMI), carbonated soft drink consumption, snoring and daytime sleepiness (Epworth sleepiness scale score), insomnia, hypertension, asthma, and usage of benzodiazepines were strong predictors of heartburn during sleep. In contrast, college education decreased the risk of reporting heartburn during sleep.

CONCLUSIONS: Heartburn during sleep is very common in the general population. Reports of this type of symptom of GERD are strongly associated with increased BMI, carbonated soft drink consumption, snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines. Overall, heartburn during sleep may be associated with sleep complaints and excessive daytime sleepiness.

}, keywords = {Aged, Body Mass Index, Carbonated Beverages, Cohort Studies, Educational Status, Female, Gastroesophageal Reflux, Heartburn, Humans, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Sleep, Surveys and Questionnaires}, issn = {0012-3692}, doi = {10.1378/chest.127.5.1658}, author = {Fass, Ronnie and Quan, Stuart F and O{\textquoteright}Connor, George T and Ervin, Ann and Iber, Conrad} } @article {937, title = {Association of physical activity with sleep-disordered breathing.}, journal = {Sleep Breath}, volume = {11}, year = {2007}, month = {2007 Sep}, pages = {149-57}, abstract = {

This study was performed to determine whether there is a protective association between participation in vigorous or vigorous/moderately vigorous physical activity and the prevalence of sleep-disordered breathing (SDB). Polysomnographic and questionnaire data from the baseline examination of 4,275 participants in the Sleep Heart Health Study (SHHS) were analyzed in relation to information on amount of physical activity and other potentially relevant factors collected from five SHHS parent cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, Strong Heart Study, and Tucson Epidemiologic Study of Airways Obstructive Diseases). Logistic regression models were fitted to determine if amount and strenuousness of physical activity was associated with the presence of SDB. At least 3 h per week of vigorous physical activity reduced the odds of SDB, defined as a respiratory disturbance index (RDI) of at least 15 apneas/hypopneas per hour (Adjusted OR, 0.68; 95\%CI, 0.51-0.91). A qualitatively similar but slightly weaker association was observed when SDB was defined as a RDI > or = 10 per hour (Adjusted OR, 0.81; 95\%CI, 0.64-1.02). These findings remained after adjustment for sleepiness and restricting analyses to participants with good health. Three or more hours of moderately vigorous or vigorous physical activity also appeared to confer some protection against SDB, but these associations were weaker. Gender- and obesity-stratified analyses suggested that the protective association between physical activity and SDB occurred primarily in men and those who were obese. A program of regular vigorous physical activity of at least 3 h per week may be a useful adjunctive treatment modality for SDB, but this association needs confirmation with a prospective clinical trial.

}, keywords = {Adult, Cardiac Rehabilitation, Cardiovascular Diseases, Cohort Studies, Exercise, Female, Humans, Longitudinal Studies, Male, Middle Aged, Obesity, Polysomnography, Pulmonary Disease, Chronic Obstructive, Pulmonary Ventilation, Risk Factors, Sex Factors, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Sleep Stages, Weight Loss}, issn = {1520-9512}, doi = {10.1007/s11325-006-0095-5}, author = {Quan, Stuart F and O{\textquoteright}Connor, George T and Quan, Jason S and Redline, Susan and Resnick, Helaine E and Shahar, Eyal and Siscovick, David and Sherrill, Duane L} } @article {989, title = {Genome-wide association of sleep and circadian phenotypes.}, journal = {BMC Med Genet}, volume = {8 Suppl 1}, year = {2007}, month = {2007 Sep 19}, pages = {S9}, abstract = {

BACKGROUND: Numerous studies suggest genetic influences on sleepiness and circadian rhythms. The Sleep Heart Health Study collected questionnaire data on sleep habits and sleepiness from 2848 Framingham Heart Study Offspring Cohort participants. More than 700 participants were genotyped using the Affymetrix 100K SNP GeneChip, providing a unique opportunity to assess genetic linkage and association of these traits.

METHODS: Sleepiness (defined as the Epworth Sleepiness Scale score), usual bedtime and usual sleep duration were assessed by self-completion questionnaire. Standardized residual measures adjusted for age, sex and BMI were analyzed. Multipoint variance components linkage analysis was performed. Association of SNPs to sleep phenotypes was analyzed with both population-based and family-based association tests, with analysis limited to 70,987 autosomal SNPs with minor allele frequency > or =10\%, call rate > or =80\%, and no significant deviation from Hardy-Weinberg equilibrium (p > or = 0.001).

RESULTS: Heritability of sleepiness was 0.29, bedtime 0.22, and sleep duration 0.17. Both genotype and sleep phenotype data were available for 749 subjects. Linkage analysis revealed five linkage peaks of LOD >2: four to usual bedtime, one to sleep duration. These peaks include several candidate sleep-related genes, including CSNK2A2, encoding a known component of the circadian molecular clock, and PROK2, encoding a putative transmitter of the behavioral circadian rhythm from the suprachiasmatic nucleus. Association tests identified an association of usual bedtime with a non-synonymous coding SNP in NPSR1 that has been shown to encode a gain of function mutation of the neuropeptide S receptor, whose endogenous ligand is a potent promoter of wakefulness. Each copy of the minor allele of this SNP was associated with a 15 minute later mean bedtime. The lowest p value was for association of sleepiness with a SNP located in an intron of PDE4D, which encodes a cAMP-specific phosphodiesterase widely expressed in human brain. Full association results are posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.

CONCLUSION: This analysis confirms prior reports of significant heritability of sleepiness, usual bedtime, and usual sleep duration. Several genetic loci with suggestive linkage to these traits are identified, including linkage peaks containing circadian clock-related genes. Association tests identify NPSR1 and PDE4D as possible mediators of bedtime and sleepiness.

}, keywords = {Adult, Alleles, Cardiovascular Diseases, Circadian Rhythm, Cohort Studies, Female, Gene Frequency, Genetic Linkage, Genome, Human, Genotype, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Sleep, Surveys and Questionnaires}, issn = {1471-2350}, doi = {10.1186/1471-2350-8-S1-S9}, author = {Gottlieb, Daniel J and O{\textquoteright}Connor, George T and Wilk, Jemma B} } @article {1202, title = {Associations of PM10 with sleep and sleep-disordered breathing in adults from seven U.S. urban areas.}, journal = {Am J Respir Crit Care Med}, volume = {182}, year = {2010}, month = {2010 Sep 15}, pages = {819-25}, abstract = {

RATIONALE: Sleep-disordered breathing (SDB), the recurrent episodic disruption of normal breathing during sleep, affects as much as 17\% of U.S. adults, and may be more prevalent in poor urban environments. SDB and air pollution have been linked to increased cardiovascular diseases and mortality, but the association between pollution and SDB is poorly understood.

OBJECTIVES: We used data from the Sleep Heart Health Study (SHHS), a U.S. multicenter cohort study assessing cardiovascular and other consequences of SDB, to examine whether particulate air matter less than 10 μm in aerodynamic diameter (PM(10)) was associated with SDB among persons 39 years of age and older.

METHODS: Using baseline data from SHHS urban sites, outcomes included the following: the respiratory disturbance index (RDI); percentage of sleep time at less than 90\% O(2) saturation; and sleep efficiency, measured by overnight in-home polysomnography. We applied a fixed-effect model containing a city effect, controlling for potential predictors. In all models we included both the 365-day moving averages of PM(10) and temperature (long-term effects) and the differences between the daily measures of these two predictors and their 365-day average (short-term effects).

MEASUREMENTS AND MAIN RESULTS: In summer, increases in RDI or percentage of sleep time at less than 90\% O(2) saturation, and decreases in sleep efficiency, were all associated with increases in short-term variation in PM(10). Over all seasons, we found that increased RDI was associated with an 11.5\% (95\% confidence interval: 1.96, 22.01) increase per interquartile range increase (25.5{\textdegree}F) in temperature.

CONCLUSIONS: Reduction in air pollution exposure may decrease the severity of SDB and nocturnal hypoxemia and may improve cardiac risk.

}, keywords = {Adult, Aged, Aged, 80 and over, Air Pollutants, Air Pollution, Cities, Cohort Studies, Female, Humans, Male, Middle Aged, Multicenter Studies as Topic, Particle Size, Particulate Matter, Polysomnography, Seasons, Severity of Illness Index, Sleep, Sleep Apnea Syndromes, Temperature, United States, Urban Health}, issn = {1535-4970}, doi = {10.1164/rccm.200912-1797OC}, author = {Zanobetti, Antonella and Redline, Susan and Schwartz, Joel and Rosen, Dennis and Patel, Sanjay and O{\textquoteright}Connor, George T and Lebowitz, Michael and Coull, Brent A and Gold, Diane R} } @article {6068, title = {Genome-wide study identifies two loci associated with lung function decline in mild to moderate COPD.}, journal = {Hum Genet}, volume = {132}, year = {2013}, month = {2013 Jan}, pages = {79-90}, abstract = {

Accelerated lung function decline is a key COPD phenotype; however, its genetic control remains largely unknown. We performed a genome-wide association study using the Illumina Human660W-Quad v.1_A BeadChip. Generalized estimation equations were used to assess genetic contributions to lung function decline over a 5-year period in 4,048 European American Lung Health Study participants with largely mild COPD. Genotype imputation was performed using reference HapMap II data. To validate regions meeting genome-wide significance, replication of top SNPs was attempted in independent cohorts. Three genes (TMEM26, ANK3 and FOXA1) within the regions of interest were selected for tissue expression studies using immunohistochemistry. Two intergenic SNPs (rs10761570, rs7911302) on chromosome 10 and one SNP on chromosome 14 (rs177852) met genome-wide significance after Bonferroni. Further support for the chromosome 10 region was obtained by imputation, the most significantly associated imputed SNPs (rs10761571, rs7896712) being flanked by observed markers rs10761570 and rs7911302. Results were not replicated in four general population cohorts or a smaller cohort of subjects with moderate to severe COPD; however, we show novel expression of genes near regions of significantly associated SNPS, including TMEM26 and FOXA1 in airway epithelium and lung parenchyma, and ANK3 in alveolar macrophages. Levels of expression were associated with lung function and COPD status. We identified two novel regions associated with lung function decline in mild COPD. Genes within these regions were expressed in relevant lung cells and their expression related to airflow limitation suggesting they may represent novel candidate genes for COPD susceptibility.

}, keywords = {Adult, Ankyrins, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 14, Cohort Studies, Female, Genome-Wide Association Study, Hepatocyte Nuclear Factor 3-alpha, Humans, Linkage Disequilibrium, Lung, Male, Membrane Proteins, Middle Aged, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive}, issn = {1432-1203}, doi = {10.1007/s00439-012-1219-6}, author = {Hansel, Nadia N and Ruczinski, Ingo and Rafaels, Nicholas and Sin, Don D and Daley, Denise and Malinina, Alla and Huang, Lili and Sandford, Andrew and Murray, Tanda and Kim, Yoonhee and Vergara, Candelaria and Heckbert, Susan R and Psaty, Bruce M and Li, Guo and Elliott, W Mark and Aminuddin, Farzian and Dupuis, Jos{\'e}e and O{\textquoteright}Connor, George T and Doheny, Kimberly and Scott, Alan F and Boezen, H Marike and Postma, Dirkje S and Smolonska, Joanna and Zanen, Pieter and Mohamed Hoesein, Firdaus A and de Koning, Harry J and Crystal, Ronald G and Tanaka, Toshiko and Ferrucci, Luigi and Silverman, Edwin and Wan, Emily and Vestbo, Jorgen and Lomas, David A and Connett, John and Wise, Robert A and Neptune, Enid R and Mathias, Rasika A and Par{\'e}, Peter D and Beaty, Terri H and Barnes, Kathleen C} } @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 {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 {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} }