PULMONARY DISEASE, CHRONIC OBSTRUCTIVE, RATE OF DECLINE OF LUNG FUNCTION IN, INCLUDED
COPD, SEVERE EARLY-ONSET, INCLUDED
COPD PULMONARY DISEASE, CHRONIC OBSTRUCTIVE, SEVERE EARLY-ONSET, INCLUDED
Chronic obstructive pulmonary disease (COPD) is a common, complex disorder associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction due to chronic bronchitis, emphysema, and/or small airways disease. Airflow obstruction is typically determined by ... Chronic obstructive pulmonary disease (COPD) is a common, complex disorder associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction due to chronic bronchitis, emphysema, and/or small airways disease. Airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) (Silverman et al., 2002; Celedon et al., 2004).
Among 201 smokers, Yamada et al. (2000) found an association between emphysema and a longer length polymorphism in the promoter region of the HMOX1 gene (141250.0003). The proportion of genotypic frequencies in the group with longer alleles was ... Among 201 smokers, Yamada et al. (2000) found an association between emphysema and a longer length polymorphism in the promoter region of the HMOX1 gene (141250.0003). The proportion of genotypic frequencies in the group with longer alleles was significantly higher in smokers with CPE than in smokers without CPE. These findings suggested that the large size of a (GT)n repeat in the HMOX1 gene promoter may reduce HMOX1 inducibility by reactive oxygen species in cigarette smoke, thereby resulting in the development of COPD. Among 749 French adults, including 40% who never smoked, Guenegou et al. (2006) observed an association between carriers of the long (L) allele of the (GT)n polymorphism and decreased lung function, as assessed by forced expiratory volume in 1 second (FEV1) and FEV1/forced ventilatory capacity (FVC) ratio, over an 8-year period (1992 to 2000). At the 8-year follow-up, the mean annual FEV1 and FEV1/FVC declines in patients with 1 or 2 L alleles were -30.9 ml/year and -1.8 U/year, FEV1/FVC decline was steeper in L allele carriers than in noncarriers (-2.6 versus -1.5, p = 0.07). There was a strong interaction between the L allele and smoking. At the 8-year follow-up, the L allele was associated with lower FEV1 and FEV1/FVC in heavy smokers only. Baseline heavy smokers carrying the L allele showed the steepest FEV1 decline (-62.0 ml/year) and the steepest FEV1/FVC decline (-8.8 U/year) (p for interaction = 0.009 and 0.0006). Guenegou et al. (2006) suggested that a long HMOX1 gene promoter in heavy smokers is associated with susceptibility to develop airway obstruction. In a 25-year study, Siedlinski et al. (2008) replicated the findings of Guenegou et al. (2006) in a large Dutch population of 1,390 individuals, including 67.9% who never smoked.