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copd genetics

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https://www.readbyqxmd.com/read/27900789/a-general-approach-to-testing-for-pleiotropy-with-rare-and-common-variants
#1
Sharon M Lutz, Tasha E Fingerlin, John E Hokanson, Christoph Lange
Through genome-wide association studies, numerous genes have been shown to be associated with multiple phenotypes. To determine the overlap of genetic susceptibility of correlated phenotypes, one can apply multivariate regression or dimension reduction techniques, such as principal components analysis, and test for the association with the principal components of the phenotypes rather than the individual phenotypes. However, as these approaches test whether there is a genetic effect for at least one of the phenotypes, a significant test result does not necessarily imply pleiotropy...
November 30, 2016: Genetic Epidemiology
https://www.readbyqxmd.com/read/27891067/are-healthy-smokers-really-healthy
#2
REVIEW
Zijing Zhou, Ping Chen, Hong Peng
Cigarette smoke contains more than 4500 chemicals which have toxic, mutagenic and carcinogenic effects. Strong evidences have shown that current smokers take a significantly higher risk of cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and lung cancer than nonsmokers. However, less attention has been paid to the smoking induced abnormalities in the individuals defined as healthy smokers who are normal with spirometry, radiographic images, routine physical exam and categorized as healthy control group in many researches...
2016: Tobacco Induced Diseases
https://www.readbyqxmd.com/read/27886851/the-role-of-necroptosis-in-pulmonary-diseases
#3
REVIEW
Kenji Mizumura, Shuichiro Maruoka, Yasuhiro Gon, Augustine M K Choi, Shu Hashimoto
By regulating the cell number and eliminating harmful cells, programmed cell death plays a critical role in development, homeostasis, and disease. While apoptosis is a recognized form of programmed cell death, necrosis was considered a type of uncontrolled cell death induced by extreme physical or chemical stress. However, recent studies have revealed the existence of a genetically programmed and regulated form of necrosis, termed necroptosis. Necroptosis is defined as necrotic cell death that is dependent on receptor-interacting protein kinase 3 (RIPK3)...
November 2016: Respiratory Investigation
https://www.readbyqxmd.com/read/27885911/end-of-life-prognostic-indicators-in-patients-with-copd-part-2
#4
Andy Parry, Ray Higginson, Aoife Gleeson
In the UK, chronic respiratory diseases cause 13% of adult disability. The major chronic respiratory disease is chronic obstructive pulmonary disease (COPD), a condition involving chronic airway inflammation that causes airflow obstruction and destruction of lung tissue. This leads to a progressive loss of respiratory membrane, which accounts for the clinical manifestation of COPD, which is difficulty maintaining sufficient gas exchange to meet metabolic demands. The primary cause is smoking, with the vast majority of COPD patients having a past or present history of smoking...
November 2, 2016: International Journal of Palliative Nursing
https://www.readbyqxmd.com/read/27878470/%C3%AE-2-agonists
#5
Charlotte K Billington, Raymond B Penn, Ian P Hall
History suggests β agonists, the cognate ligand of the β2 adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the frontline treatment for asthma and chronic obstructive pulmonary disease (COPD). The β agonists used clinically today are the products of significant expenditure and over 100 year's intensive research aimed at minimizing side effects and enhancing therapeutic usefulness. The respiratory physician now has a therapeutic toolbox of long acting β agonists to prophylactically manage bronchoconstriction, and short acting β agonists to relieve acute exacerbations...
November 23, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27875557/socioeconomic-status-and-poor-health-outcome-at-10-years-of-follow-up-in-the-multi-ethnic-study-of-atherosclerosis
#6
Steven Shea, Joao Lima, Ana Diez-Roux, Neal W Jorgensen, Robyn L McClelland
BACKGROUND/OBJECTIVES: Predictors of healthy aging have not been well-studied using longitudinal data with demographic, clinical, subclinical, and genetic information. The objective was to identify predictors of poor health outcome at 10 years of follow-up in the Multi-Ethnic Study of Atherosclerosis (MESA). DESIGN: Prospective cohort study. SETTING: Population-based sample from 6 U.S. communities. PARTICIPANTS: 4,355 participants In the MESA Study...
2016: PloS One
https://www.readbyqxmd.com/read/27857848/the-effect-of-%C3%AE-1-antitrypsin-deficiency-combined-with-increased-bacterial-loads-on-chronic-obstructive-pulmonary-disease-pharmacotherapy-a-prospective-parallel-controlled-pilot-study
#7
Marwa G Hennawy, Noha M Elhosseiny, Hussein Sultan, Wael Abdelfattah, Yousry Akl, Nirmeen A Sabry, Ahmed S Attia
Chronic obstructive pulmonary disease (COPD) is caused by α1-antitrypsin deficiency (AATD) genetic susceptibility and exacerbated by infection. The current pilot study aimed at studying the combined effect of AATD and bacterial loads on the efficacy of COPD conventional pharmacotherapy. Fifty-nine subjects (29 controls and 30 COPD patients) were tested for genetic AATD and respiratory function. The bacterial loads were determined to the patients' group who were then given a long acting beta-agonist and corticosteroid inhaler for 6 months...
November 2016: Journal of Advanced Research
https://www.readbyqxmd.com/read/27854507/sex-based-genetic-association-study-identifies-celsr1-as-a-possible-copd-risk-locus-among-women
#8
Megan Hardin, Michael H Cho, Sunita S Sharma, Kimberly Glass, Peter J Castaldi, Merry-Lynn McDonald, Hugues Aschard, Jody Senter-Sylvia, Kelan Tantisira, Scott T Weiss, Craig P Hersh, Jarrett D Morrow, David Lomas, Alvar Agusti, Per Bakke, Amund Gulsvik, George T O'Connor, Josée Dupuis, John Hokanson, James Crapo, Terri H Beaty, Nan Laird, Edwin K Silverman, Dawn L DeMeo
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a complex disease with strong environmental and genetic influences and sexually dimorphic features. Although genetic risk factors for COPD have been identified, much of the heritability remains unexplained. Sex-based genetic association studies may uncover additional COPD genetic risk factors. METHODS: We studied current and former smokers from COPD case-control cohorts (COPDGene non-Hispanic whites and African Americans, ECLIPSE, and GenKOLS)...
November 17, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27835950/targeted-high-throughput-sequencing-of-candidate-genes-for-chronic-obstructive-pulmonary-disease
#9
Hans Matsson, Cilla Söderhäll, Elisabet Einarsdottir, Maxime Lamontagne, Sanna Gudmundsson, Helena Backman, Anne Lindberg, Eva Rönmark, Juha Kere, Don Sin, Dirkje S Postma, Yohan Bossé, Bo Lundbäck, Joakim Klar
BACKGROUND: Reduced lung function in patients with chronic obstructive pulmonary disease (COPD) is likely due to both environmental and genetic factors. We report here a targeted high-throughput DNA sequencing approach to identify new and previously known genetic variants in a set of candidate genes for COPD. METHODS: Exons in 22 genes implicated in lung development as well as 61 genes and 10 genomic regions previously associated with COPD were sequenced using individual DNA samples from 68 cases with moderate or severe COPD and 66 controls matched for age, gender and smoking...
November 11, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27830153/genetic-polymorphism-of-angiotensin-converting-enzyme-and-chronic-obstructive-pulmonary-disease-risk-an-updated-meta-analysis
#10
REVIEW
Sang Wook Kang, Su Kang Kim, Joo-Ho Chung, Hee-Jae Jung, Kwan-Il Kim, Jinju Kim, Ju Yeon Ban
The relationship between polymorphism of the angiotensin I converting enzyme (ACE) gene and chronic obstructive pulmonary disease (COPD) has been examined in many previous studies. However, their results were controversial. Therefore, we performed a meta-analysis to evaluate the relationship between the ACE gene and the risk of COPD. Fourteen case-control studies were included in this meta-analysis. The pooled p value, odds ratio (OR), and 95% confidence interval (95% CI) were used to investigate the strength of the association...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27826243/genetic-ablation-of-cxcr2-protects-against-cigarette-smoke-induced-lung-inflammation-and-injury
#11
Chad A Lerner, Wei Lei, Isaac K Sundar, Irfan Rahman
Antagonism of CXCR2 receptors, predominately located on neutrophils and critical for their immunomodulatory activity, is an attractive pharmacological therapeutic approach aimed at reducing the potentially damaging effects of heightened neutrophil influx into the lung. The role CXCR2 in lung inflammation in response to cigarette smoke (CS) inhalation using the mutant mouse approach is not known. We hypothesized that genetic ablation of CXCR2 would protect mice against CS-induced inflammation and DNA damage response...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27824593/the-prevalence-of-diagnosed-%C3%AE-1-antitrypsin-deficiency-and-its-comorbidities-results-from-a-large-population-based-database
#12
Timm Greulich, Christoph Nell, David Hohmann, Marco Grebe, Sabina Janciauskiene, Andreas Rembert Koczulla, Claus Franz Vogelmeier
α1-Antitrypsin deficiency (AATD) is a genetically determined disorder that is associated with different clinical manifestations. We aimed to assess the prevalence of diagnosed AATD and its comorbidities using a large healthcare database.In this retrospective longitudinal observational study, we analysed data from 4 million insurants. Using International Classification of Diseases revision 10 (ICD-10) codes, we assessed the prevalence, comorbidities and healthcare utilisation of AATD patients (E88.0 repeatedly coded) relative to non-AATD patients with chronic obstructive pulmonary disease (COPD), emphysema or asthma...
October 20, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27812370/post-gwas-prioritization-through-data-integration-provides-novel-insights-on-chronic-obstructive-pulmonary-disease
#13
Qiongshi Lu, Chentian Jin, Jiehuan Sun, Russell Bowler, Katerina Kechris, Naftali Kaminski, Hongyu Zhao
Rich collections of genomic and epigenomic annotations, availabilities of large population cohorts for genome-wide association studies (GWAS), and advancements in data integration techniques provide the unprecedented opportunity to accelerate discoveries in complex disease studies through integrative analyses. In this paper, we apply a variety of approaches to integrate GWAS summary statistics of chronic obstructive pulmonary disease (COPD) with functional annotations to illustrate how data integration could help researchers understand complex human diseases...
2016: Statistics in Biosciences
https://www.readbyqxmd.com/read/27802088/end-of-life-prognostic-indicators-in-patients-with-copd-part-1
#14
Aoife Gleeson, Andy Parry, Ray Higginson
In the UK, chronic respiratory diseases cause 13% of adult disability. The major chronic respiratory disease is chronic obstructive pulmonary disease (COPD), a condition involving chronic airway inflammation that causes airflow obstruction and destruction of lung tissue. This leads to a progressive loss of respiratory membrane, which accounts for the clinical manifestation of COPD, which is difficulty maintaining sufficient gas exchange to meet metabolic demands. The primary cause is smoking, with the vast majority of COPD patients having a past or present history of smoking...
October 2, 2016: International Journal of Palliative Nursing
https://www.readbyqxmd.com/read/27795984/pulmonary-predictors-of-incident-diabetes-in-smokers
#15
Gregory L Kinney, Emma H Baker, Oana L Klein, Jennifer L Black-Shinn, Emily S Wan, Barry Make, Elizabeth Regan, Russell P Bowler, Sharon M Lutz, Kendra A Young, Lindsey M Duca, George R Washko, Edwin K Silverman, James D Crapo, John E Hokanson
BACKGROUND: Diabetes mellitus and its complications are a large and increasing burden for health care worldwide. Reduced pulmonary function has been observed in diabetes (both type 1 and type 2), and this reduction is thought to occur prior to diagnosis. Other measures of pulmonary health are associated with diabetes, including lower exercise tolerance, greater dyspnea, lower quality of life (as measured by the St. George's Respiratory Questionaire [SGRQ]) and susceptibility to lung infection and these measures may also predate diabetes diagnosis...
2016: Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation
https://www.readbyqxmd.com/read/27789940/trpm8-genetic-variations-associated-with-copd-risk-in-the-chinese-han-population
#16
Mingmei Xiong, Jian Wang, Meihua Guo, Qipeng Zhou, Wenju Lu
TRPM8 plays a key role in COPD. The development of pulmonary hypertension (PH) in COPD adversely affects survival and exercise capacity. Thus, the aim of this study was to evaluate the possible association between single nucleotide polymorphisms (SNPs) in TRPM8 and COPD or PH in COPD among the Chinese Han population. A total of 513 COPD patients and 506 controls were enrolled in the study. Six tag SNPs (tSNPs) were genotyped. The relationship between COPD or PH in COPD and the six tSNPs was evaluated using the χ(2) test and genetic model analysis...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27771979/recent-advances-in-understanding-and-treating-copd-related-to-%C3%AE-1-antitrypsin-deficiency
#17
Maria Paula Henao, Timothy J Craig
Alpha-1-antitrypsin deficiency (AATD) is an orphan disease that predisposes individuals to COPD and liver disease. The following is a comprehensive review of AATD from epidemiology to treatment for physicians who treat COPD or asthma. Areas covered: In this comprehensive review of alpha-1-antitrypsin deficiency, we describe the historical perspective, genetics, epidemiology, clinical presentation and symptoms, screening and diagnosis, and treatments of the condition. Expert commentary: The two most important directions for advancing the understanding of AATD involve improving detection of the condition, especially in asymptomatic patients, and advancing knowledge of treatments directed specifically at AATD-related conditions...
November 4, 2016: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/27748465/phenomenology-of-copd-interpreting-phenotypes-with-the-eclipse-study
#18
Alberto Papi, Maria Sandra Magnoni, Carmelo Caio Muzzio, Gianmarco Benso, Andrea Rizzi
The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study was a large 3-year observational multicentre international study aimed at defining COPD phenotypes and identifying biomarkers and/or genetic parameters that help to predict disease progression. The study has contributed to a better understanding of COPD heterogeneity, with the characterization of clinically important subtypes/phenotypes of patients, such as the frequent exacerbators or patient with persistent systemic inflammation, who may have different prognosis or treatment requirements...
October 14, 2016: Monaldi Archives for Chest Disease, Archivio Monaldi Per le Malattie del Torace
https://www.readbyqxmd.com/read/27739898/visual-assessment-of-chest-ct-images-is-independently-useful-for-genetic-association-analysis-in-studies-of-chronic-obstructive-pulmonary-disease
#19
Eitan Halper-Stromberg, Michael H Cho, Carla Wilson, Dipti Nevrekar, James D Crapo, George Washko, Raúl San José Estépar, David A Lynch, Edwin K Silverman, Sonia Leach, Peter J Castaldi
RATIONALE: Automated analysis of computed tomographic (CT) lung images for epidemiologic nand genetic association studies is increasingly common, but little is known about the utility of visual versus semi-automated emphysema and airway assessments for genetic association studies. OBJECTIVES: Assess the relative utility of visual versus semi-automated emphysema and airway assessments for genetic association studies. METHODS: A standardized inspection protocol was used to visually assess chest CTs for 1540 non-Hispanic white subjects within the COPDGene Study for the presence and severity of radiographic features representing airway wall thickness and emphysema...
October 14, 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27730172/genetic-regulation-of-expression-of-leukotriene-a4-hydrolase
#20
Tomasz Szul, Peter Castaldi, Michael H Cho, J Edwin Blalock, Amit Gaggar
In chronic inflammatory lung disorders such as chronic obstructive pulmonary disease (COPD), the concurrent organ-specific and systemic inflammatory responses lead to airway remodelling and vascular dysfunction. Although a major common risk factor for COPD, cigarette smoke alone cannot explain the progression of this disease; there is increasing evidence that genetic predisposition also plays a role in COPD susceptibility and progression. A key enzyme in chronic lung inflammation is leukotriene A4 hydrolase (LTA4H)...
January 2016: ERJ Open Research
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