Genetic Mechanisms of Chronic Obstructive Pulmonary Disease (COPD)
The purpose of this study is to determine whether genetic factors contribute to an individuals risk of developing obstructive lung disease from smoking cigarettes.
Chronic obstructive pulmonary disease (COPD) is among the most important chronic diseases of adults. It is the fourth leading cause of death in the U.S. and affects more than 10% of the U.S. population over age 55. COPD accounts for more than 25,000 discharges annually from VA medical centers. Cigarette smoking is the most important known modifiable cause of COPD, yet only 15-20% of cigarette smokers develop clinically significant COPD. We therefore hypothesize that genetic mechanisms determine susceptibility to the development of COPD. The only genetic abnormality known to cause COPD is deficiency of the serine protease inhibitor 1-protease inhibitor, which causes premature development of emphysema, although it is implicated in fewer than 2% of COPD cases. Several other genetic variants have been proposed as candidate causes of COPD; however, these have been identified on the basis of association studies in unrelated subjects, which have considerable risk of ascertainment bias. In the present study, a sub-pair linkage approach will be utilized in COPD patients and their smoking siblings to identify genes which determine the risk of developing COPD. The following are the short-term objectives of this study:
1. Recruit a cohort of 400 probands with smoking-related COPD and their smoking siblings, whether or not affected by COPD. Affected subjects will be extensively characterized as to specific COPD phenotype, using spirometry, computed tomography, and questionnaire data.
2. Test the association of known genetic variants in candidate genes to the presence of COPD.
3. For proposed candidate genes without known candidate polymorphisms, use sib-pair linkage analysis to test polymorphic marker loci in close proximity to the candidate gene for evidence of linkage to COPD.
4. Test for heterogeneity of linkage among different COPD phenotypes: predominant emphysema versus predominant airway disease.
The long-term objective of this research is the identification of specific genetic variants which confer risk for the development of COPD in smokers. This will be achieved by means of fine mapping of the loci identified in objectives 3-4 above, or in a subsequent genome scan involving the 400 sibling pairs; identification of novel genetic variants at these loci; and assessment of the functional significance of these variants and their relation to COPD in an independent sample of subjects.
Recruitment of subjects for this project began in April, 1999. At this time, a total of 22 subjects (11 COPD patients and 11 first-degree relatives) have been recruited and tested. No adverse events have occurred. A computerized methodology for quantitation of emphysema from CT scans has been developed and has demonstrated adequate DNA extraction from our blood samples. Genotyping has been deferred pending the recruitment of 50 subjects.
Time Perspective: Retrospective
Chronic Obstructive Lung Disease
VA Boston Healthcare System
Department of Veterans Affairs
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00018408
- Information obtained from ClinicalTrials.gov on July 15, 2010
The purpose of the study is to investigate, in patients with moderate to severe chronic obstructive lung disease, whether intermittent antibiotic treatment leads to: - A slower rate...
This is a study of the lung health of the population of Vancouver and the extent of, and the risk factors for, chronic obstructive lung disease.
RATIONALE: Exercise may help improve lung function and lessen complications of surgery in patients with chronic obstructive pulmonary disease who are undergoing surgery for lung cancer. It...
It is not clear whether antibiotic therapy is needed in patients with mild to moderate exacerbation of chronic obstructive lung disease. The aim of the study is to compare the effect of 1 ...
Tadalafil may lower the pulmonary artery pressure in patients with Chronic Obstructive Lung Disease and secondary pulmonary hypertension and thereby improve patients quality of life.
This review discusses the recent Asian chronic obstructive lung disease (COPD) studies that characterize stable COPD, to understand its peculiarities.
The Korean Obstructive Lung Disease (KOLD) Cohort Study is a prospective longitudinal study of patients with chronic obstructive pulmonary disease (COPD), asthma, or other unclassified obstructive lun...
Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease resulting from exposure to cigarette smoke, noxious gases, particulate matter, and air pollutants. COPD is exacerbat...
Chronic obstructive pulmonary disease (COPD) is a chronic, progressive disease and is treated with inhaled medication to optimize the patient's lung health through decreasing their symptoms, especiall...
The prevalence of chronic obstructive pulmonary disease (COPD) in females appears to be increasing. Recent studies have revealed that the percentage of women with COPD in Greece is approximately 12.5%...
Medical and Biotech [MESH] Definitions
A condition associated with multiple episodes of sleep apnea which are distinguished from obstructive sleep apnea (SLEEP APNEA, OBSTRUCTIVE) by the complete cessation of efforts to breathe. This disorder is associated with dysfunction of central nervous system centers that regulate respiration. This condition may be idiopathic (primary) or associated with lower brain stem lesions; chronic obstructive pulmonary disease (LUNG DISEASES, OBSTRUCTIVE); HEART FAILURE, CONGESTIVE; medication effect; and other conditions. Sleep maintenance is impaired, resulting in daytime hypersomnolence. Primary central sleep apnea is frequently associated with obstructive sleep apnea. When both forms are present the condition is referred to as mixed sleep apnea (see SLEEP APNEA SYNDROMES). (Adams et al., Principles of Neurology, 6th ed, p395; Neurol Clin 1996;14(3):611-28)
A subcategory of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis.
A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.
Any disorder marked by obstruction of conducting airways of the lung. AIRWAY OBSTRUCTION may be acute, chronic, intermittent, or persistent.
Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.