Genetic and Environmental Determinants of Chronic Obstructive Pulmonary Disease
01 May 1970-Annals of Internal Medicine (American College of Physicians)-Vol. 72, Iss: 5, pp 627-631
TL;DR: The prevalence of abnormalities of pulmonary function among 156 relatives of 61 patients with chronic obstructive pulmonary disease was found to be significantly higher than the prevalence of the disease itself.
Abstract: The prevalence of abnormalities of pulmonary function among 156 relatives of 61 patients with chronic obstructive pulmonary disease was found to be significantly higher than the prevalence...
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TL;DR: The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking.
Abstract: Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-1-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. Assessment of the risk to relatives of these early-onset COPD probands for airflow obstruction and chronic bronchitis was performed to determine whether significant familial aggregation for COPD, independent of alpha-1-antitrypsin deficiency, could be demonstrated. First- degree relatives of early-onset COPD probands had significantly lower FEV1 and FEV1/FVC values than control subjects (p < 0.01), despite similar pack-years of smoking. Reduced spirometric values in first-degree relatives of early-onset COPD probands were found only in current or ex-cigarette smokers. The mean FEV1 in current or ex-smoking first-degree relatives was 76.1 +/- 20.9% predicted compared to 89.2 +/- 14.4% predicted in current or ex-smoking control subjects (p < 0.01); in lifelong nonsmokers, the mean FEV1 was 93.4% predicted for both control subjects and first-degree relatives of early-onset COPD probands. Generalized estimating equations, adjusting for age and pack-years of smoking, demonstrated increased odds of reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree relatives of early-onset COPD probands. Using a new method to estimate relative risk from relative odds, we estimate that the relative risks for FEV1 below 60%, FEV1 below 80%, and chronic bronchitis are each approximately three in current or ex-smoking first-degree relatives of early-onset COPD probands. The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking.
381 citations
TL;DR: It is concluded that the prevalence of depression in patients with moderate or severe COPD approaches 50 percent while the incidence of anxiety is much lower (2 percent).
262 citations
TL;DR: A detailed literature review of the genes which have been investigated as potential risk factors for chronic obstructive pulmonary disease is presented.
Abstract: Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only a minority of cigarette smokers develop symptomatic disease. Studies of families and twins suggest that genetic factors also contribute to the development of COPD. We present a detailed literature review of the genes which have been investigated as potential risk factors for this disease. The only established genetic risk factor for COPD is homozygosity for the Z allele of the alpha1-antitrypsin gene. Heterozygotes for the Z allele may also be at increased risk. Other mutations affecting the structure of alpha1-antitrypsin or the regulation of gene expression have been identified as risk factors. Genes, including those for alpha1-antichymotrypsin, alpha2-macroglobulin, vitamin D-binding protein and blood group antigens, have also been associated with the development of COPD. Variants of the cystic fibrosis transmembrane regulator gene have been identified as risk factors for disseminated bronchiectasis. The genetic basis to chronic obstructive pulmonary disease has begun to be elucidated and it is likely that several genes will be implicated in the pathogenesis of this disease. The knowledge gained from such studies may also prove relevant to other inflammatory diseases.
231 citations
TL;DR: In this article, the authors quantified the risk of airflow obstruction in siblings of patients with chronic obstructive pulmonary disease (COPD) and found that siblings with less than a 30 pack-year smoking history were more likely to develop COPD.
Abstract: Although familial clustering has been described, few studies have quantified the risk of airflow obstruction in siblings of patients with chronic obstructive pulmonary disease (COPD). One hundred fifty-two subjects with airflow obstruction and a low gas transfer factor (but without PiZ alpha(1)-antitrypsin deficiency) were identified and 150 were enrolled in the study. Complete data were obtained from 173 of 221 siblings of these subjects. Forty-four of 126 current or ex-smoking siblings had airflow obstruction (FEV(1)/FVC < 0.7) and 36 also had a FEV(1) < 80% predicted, in keeping with COPD. One hundred eleven current or ex-smoking siblings were matched for age, sex, and smoking history with 419 subjects, without a known family history of COPD, from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort. The prevalence of COPD was much lower in the EPIC group (9.3%) when compared with the siblings (31.5%; odds ratio, 4.70; 95% confidence interval, 2.63 to 8.41). The odds ratio for COPD in siblings with less than a 30 pack-year smoking history was 5.39 (95% confidence interval, 2.49 to 11.67) when compared with matched control subjects. Taken together these results demonstrate a significant familial risk of airflow obstruction in smoking siblings of patients with severe COPD.
180 citations
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TL;DR: A deficiency of alpha 1 -antitrypsin may be an important etiologic factor in the development of destructive lung disease occurring at a relatively young age and the rapid deterioration observed in patients may be related to this deficiency.
167 citations
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