@article {1455, title = {Asthma and its association with cardiovascular disease in the elderly. The Cardiovascular Health Study Research Group.}, journal = {J Asthma}, volume = {33}, year = {1996}, month = {1996}, pages = {45-53}, abstract = {

Cardiovascular disease (CVD) is more prevalent in elderly than in middle-aged patients. Symptoms such as intermittent wheezing with dyspnea may then be due to either CVD or asthma. The objective of this study was to determine the prevalence and correlates of asthma in the elderly and their associations with CVD and CVD risk factors. A community sample of 5201 elderly persons from the Cardiovascular Health Study was asked if they had a physician diagnosis of asthma, and multiple cardiovascular risk and disease variables were measured. Six percent of the participants (309) recalled a history of asthma, and half of these were never smokers. Thirty percent of those with asthma were currently taking a bronchodilator, 14\% inhaled steroids, and 10\% oral prednisone. Men and women with asthma who were cigarette smokers were more likely to report a concurrent diagnosis of congestive heart failure than smokers without asthma (p = .04). However, when we determined the independent CVD correlates of asthma in this cohort, controlling for smoking status, age, gender, and diagnoses of chronic bronchitis and emphysema, only higher levels of high-density lipoprotein cholesterol (HDL-C) and higher plasma fibrinogen levels were significantly associated with asthma. It was concluded that asthma is as prevalent in the elderly as in middle-aged persons and is associated with higher HDL-C and higher fibrinogen levels, but not with prevalent cardiovascular disease.

}, keywords = {Aged, Aged, 80 and over, Asthma, Cardiovascular Diseases, Cohort Studies, Female, Humans, Lung, Male, Multivariate Analysis, Prevalence, Risk Factors, Sex Distribution, Smoking}, issn = {0277-0903}, author = {Enright, P L and Ward, B J and Tracy, R P and Lasser, E C} } @article {1462, title = {Lipoprotein levels in elderly patients with asthma. Cardiovascular Health Study Research Group.}, journal = {J Allergy Clin Immunol}, volume = {98}, year = {1996}, month = {1996 Aug}, pages = {467-9}, keywords = {Aged, Aging, Arteriosclerosis, Asthma, Female, Humans, Lipoproteins, Male, Prospective Studies, Risk Factors, Sex Factors}, issn = {0091-6749}, author = {Enright, P L and Lasser, E C and Ward, B J and Tracy, R P} } @article {601, title = {Underdiagnosis and undertreatment of asthma in the elderly. Cardiovascular Health Study Research Group.}, journal = {Chest}, volume = {116}, year = {1999}, month = {1999 Sep}, pages = {603-13}, abstract = {

OBJECTIVE: To describe the clinical correlates of asthma in a community-based sample of elderly persons.

PARTICIPANTS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study.

MEASUREMENTS: Standardized respiratory, sleep, and quality-of-life (QOL) questions, a medication inventory, spirometry, and ambulatory peak flow.

RESULTS: Four percent of the participants reported a current diagnosis of asthma (definite asthma), while another 4\% reported at least one attack of wheezing accompanied by chest tightness or dyspnea during the previous 12 months (probable asthma). Smokers and those with congestive heart failure were excluded from the subsequent analyses, leaving 2,527 participants. Of those who had definite asthma, 40\% were taking a sympathomimetic bronchodilator, 30\% inhaled corticosteroids, 21\% theophylline, and 18\% oral corticosteroids; 39\% were taking no asthma medications. The participants with definite or probable asthma were much more likely than the others to have a family history of asthma, childhood respiratory problems, a history of workplace exposures, dyspnea on exertion, hay fever, chronic bronchitis, nocturnal symptoms, and daytime sleepiness. They were also more likely to report poor general health, symptoms of depression, and limitation of activities of daily living. There was little difference in the morbidity and QOL of participants with recent asthma-like symptoms who had received the diagnosis of asthma versus those who had not.

CONCLUSIONS: Asthma in elderly persons is associated with a lower QOL and considerable morbidity when compared with those who do not have asthma symptoms. Asthma is underdiagnosed in this group and is often associated with allergic triggers; inhaled corticosteroids are underutilized.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Asthma, Female, Humans, Male, Peak Expiratory Flow Rate, Quality of Life, Risk Factors, Spirometry, Vital Capacity}, issn = {0012-3692}, doi = {10.1378/chest.116.3.603}, author = {Enright, P L and McClelland, R L and Newman, A B and Gottlieb, D J and Lebowitz, M D} } @article {671, title = {Correlates of peak expiratory flow lability in elderly persons.}, journal = {Chest}, volume = {120}, year = {2001}, month = {2001 Dec}, pages = {1861-8}, abstract = {

OBJECTIVE: To determine the correlates of the lability of peak expiratory flow (PEF) in the elderly.

METHODS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study completed an asthma questionnaire and underwent spirometry. During a follow-up examination of the cohort, 1,836 persons agreed to measure PEF at home twice daily for 2 weeks, and 90\% successfully obtained at least 4 days of valid measurements. PEF lability was calculated as the highest daily (PEF maximum - PEF minimum)/mean PEF.

RESULTS: Mean PEF measured at home was accurate when compared to PEF determined by spirometry in the clinic. Mean PEF lability was 18\% in those with current asthma (n = 165) vs 12\% in healthy nonsmokers (upper limit of normal, 29\%). Approximately 26\% of those with asthma and 14\% of the other participants had abnormally high PEF lability (> 29\%). After excluding participants with asthma, other independent predictors of high PEF lability included black race, current and former smoking, airway obstruction on spirometry, daytime sleepiness, recent wheezing, chronic cough, emphysema, and wheezing from lying in a supine position. Despite having a lower mean PEF, those reporting congestive heart failure (n = 82) did not have significantly higher PEF lability.

CONCLUSIONS: Measurement of PEF lability at home is highly successful in elderly persons. PEF lability > or = 30\% is abnormal in the elderly and is associated with asthma.

}, keywords = {Aged, Aged, 80 and over, Aging, Asthma, Female, Heart Failure, Humans, Male, Monitoring, Ambulatory, Peak Expiratory Flow Rate, Predictive Value of Tests, Pulmonary Disease, Chronic Obstructive, Reference Values, Rhinitis, Allergic, Seasonal, Risk Factors, Signal Processing, Computer-Assisted, Spirometry}, issn = {0012-3692}, doi = {10.1378/chest.120.6.1861}, author = {Enright, P L and McClelland, R L and Buist, A S and Lebowitz, M D} } @article {7577, title = {Rare coding variants pinpoint genes that control human hematological traits.}, journal = {PLoS Genet}, volume = {13}, year = {2017}, month = {2017 Aug}, pages = {e1006925}, abstract = {

The identification of rare coding or splice site variants remains the most straightforward strategy to link genes with human phenotypes. Here, we analyzed the association between 137,086 rare (minor allele frequency (MAF) <1\%) coding or splice site variants and 15 hematological traits in up to 308,572 participants. We found 56 such rare coding or splice site variants at P<5x10-8, including 31 that are associated with a blood-cell phenotype for the first time. All but one of these 31 new independent variants map to loci previously implicated in hematopoiesis by genome-wide association studies (GWAS). This includes a rare splice acceptor variant (rs146597587, MAF = 0.5\%) in interleukin 33 (IL33) associated with reduced eosinophil count (P = 2.4x10-23), and lower risk of asthma (P = 2.6x10-7, odds ratio [95\% confidence interval] = 0.56 [0.45-0.70]) and allergic rhinitis (P = 4.2x10-4, odds ratio = 0.55 [0.39-0.76]). The single new locus identified in our study is defined by a rare p.Arg172Gly missense variant (rs145535174, MAF = 0.05\%) in plasminogen (PLG) associated with increased platelet count (P = 6.8x10-9), and decreased D-dimer concentration (P = 0.018) and platelet reactivity (P<0.03). Finally, our results indicate that searching for rare coding or splice site variants in very large sample sizes can help prioritize causal genes at many GWAS loci associated with complex human diseases and traits.

}, keywords = {Asthma, Databases, Genetic, Endometriosis, Female, Fibrin Fibrinogen Degradation Products, Gene Frequency, Genetic Loci, Genome, Human, Genome-Wide Association Study, Humans, Interleukin-33, Linear Models, Logistic Models, Male, Mutation, Missense, Phenotype, Plasminogen, Platelet Count, Polymorphism, Single Nucleotide, Principal Component Analysis, Protein Splicing, Rhinitis, Allergic, Sequence Analysis, DNA}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1006925}, author = {Mousas, Abdou and Ntritsos, Georgios and Chen, Ming-Huei and Song, Ci and Huffman, Jennifer E and Tzoulaki, Ioanna and Elliott, Paul and Psaty, Bruce M and Auer, Paul L and Johnson, Andrew D and Evangelou, Evangelos and Lettre, Guillaume and Reiner, Alexander P} } @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 {8914, title = {Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program.}, journal = {Am J Hum Genet}, volume = {108}, year = {2021}, month = {2021 10 07}, pages = {1836-1851}, abstract = {

Many common and rare variants associated with hematologic traits have been discovered through imputation on large-scale reference panels. However, the majority of genome-wide association studies (GWASs) have been conducted in Europeans, and determining causal variants has proved challenging. We performed a GWAS of total leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts generated from 109,563,748 variants in the autosomes and the X chromosome in the Trans-Omics for Precision Medicine (TOPMed) program, which included data from 61,802 individuals of diverse ancestry. We discovered and replicated 7 leukocyte trait associations, including (1) the association between a chromosome X, pseudo-autosomal region (PAR), noncoding variant located between cytokine receptor genes (CSF2RA and CLRF2) and lower eosinophil count; and (2) associations between single variants found predominantly among African Americans at the S1PR3 (9q22.1) and HBB (11p15.4) loci and monocyte and lymphocyte counts, respectively. We further provide evidence indicating that the newly discovered eosinophil-lowering chromosome X PAR variant might be associated with reduced susceptibility to common allergic diseases such as atopic dermatitis and asthma. Additionally, we found a burden of very rare FLT3 (13q12.2) variants associated with monocyte counts. Together, these results emphasize the utility of whole-genome sequencing in diverse samples in identifying associations missed by European-ancestry-driven GWASs.

}, keywords = {Asthma, Biomarkers, Dermatitis, Atopic, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Leukocytes, National Heart, Lung, and Blood Institute (U.S.), Phenotype, Polymorphism, Single Nucleotide, Prognosis, Proteome, Pulmonary Disease, Chronic Obstructive, Quantitative Trait Loci, United Kingdom, United States, Whole Genome Sequencing}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2021.08.007}, author = {Mikhaylova, Anna V and McHugh, Caitlin P and Polfus, Linda M and Raffield, Laura M and Boorgula, Meher Preethi and Blackwell, Thomas W and Brody, Jennifer A and Broome, Jai and Chami, Nathalie and Chen, Ming-Huei and Conomos, Matthew P and Cox, Corey and Curran, Joanne E and Daya, Michelle and Ekunwe, Lynette and Glahn, David C and Heard-Costa, Nancy and Highland, Heather M and Hobbs, Brian D and Ilboudo, Yann and Jain, Deepti and Lange, Leslie A and Miller-Fleming, Tyne W and Min, Nancy and Moon, Jee-Young and Preuss, Michael H and Rosen, Jonathon and Ryan, Kathleen and Smith, Albert V and Sun, Quan and Surendran, Praveen and de Vries, Paul S and Walter, Klaudia and Wang, Zhe and Wheeler, Marsha and Yanek, Lisa R and Zhong, Xue and Abecasis, Goncalo R and Almasy, Laura and Barnes, Kathleen C and Beaty, Terri H and Becker, Lewis C and Blangero, John and Boerwinkle, Eric and Butterworth, Adam S and Chavan, Sameer and Cho, Michael H and Choquet, Helene and Correa, Adolfo and Cox, Nancy and DeMeo, Dawn L and Faraday, Nauder and Fornage, Myriam and Gerszten, Robert E and Hou, Lifang and Johnson, Andrew D and Jorgenson, Eric and Kaplan, Robert and Kooperberg, Charles and Kundu, Kousik and Laurie, Cecelia A and Lettre, Guillaume and Lewis, Joshua P and Li, Bingshan and Li, Yun and Lloyd-Jones, Donald M and Loos, Ruth J F and Manichaikul, Ani and Meyers, Deborah A and Mitchell, Braxton D and Morrison, Alanna C and Ngo, Debby and Nickerson, Deborah A and Nongmaithem, Suraj and North, Kari E and O{\textquoteright}Connell, Jeffrey R and Ortega, Victor E and Pankratz, Nathan and Perry, James A and Psaty, Bruce M and Rich, Stephen S and Soranzo, Nicole and Rotter, Jerome I and Silverman, Edwin K and Smith, Nicholas L and Tang, Hua and Tracy, Russell P and Thornton, Timothy A and Vasan, Ramachandran S and Zein, Joe and Mathias, Rasika A and Reiner, Alexander P and Auer, Paul L} }