Longitudinal decline of diffusing capacity of the lung for carbon monoxide in community subjects with the PiMZ alpha1-antitrypsin phenotype.

BACKGROUND: It is well known that homozygous deficiency of alpha(1)-antitrypsin, PiZZ, is associated with an increased risk of emphysema. However, studies evaluating associations between the heterozygous form PiMZ with emphysema and impaired lung function have provided conflicting results. STUDY OBJECTIVE: The goal of this study was to determine if the phenotype PiMZ is associated with an accelerated decline in diffusing capacity of the lung for carbon monoxide (Dlco). DESIGN AND METHODS: The Tucson Epidemiologic Study of Airway Obstructive Disease is a prospective, population-based cohort study initiated in 1972. Participants completed standardized questionnaires in up to 12 periodic surveys and Dlco assessments in up to 4 surveys. Random-effects models were used to determine the effects of alpha(1)-antitrypsin phenotypes on percentage of predicted (% predicted) Dlco levels among 1,075 subjects > or = 18 years old. RESULTS: % predicted Dlco declined more rapidly in subjects who smoked compared to nonsmoking subjects. Additionally, in smokers, the PiMZ phenotype was associated with borderline % predicted Dlco deficits at age 40 years (8.6%; p = 0.075) and significant % predicted Dlco deficits at age 60 years (15.2%; p = 0.001) and 80 years (21.9%; p = 0.003), as compared with the PiMM phenotype. CONCLUSIONS: Dlco may be a more sensitive indicator of the long-term effects of intermediate levels of alpha(1)-antitrypsin on lung function especially in subjects who smoke.

A longitudinal study of alpha1-antitrypsin phenotypes and decline in FEV1 in a community population.

BACKGROUND: It is well-known that the homozygous deficiency of alpha(1)-antitrypsin, phenotype PiZZ, is associated with an increased risk of COPD. However, studies evaluating the association between the heterozygous forms of the alpha(1)-antitrypsin phenotype PiMZ and rapid decline in lung function, both in patient and community populations, have yielded conflicting results. STUDY OBJECTIVE: To assess the relationship between alpha(1)-antitrypsin phenotypes and decline in FEV(1) values of 2,016 adult subjects in a community population in Tucson, AZ. DESIGN AND METHODS: Prospective cohort study. Standardized questionnaires and lung function measurements were administered 1.5 to 2 years apart during 12 surveys. RESULTS: The frequency distribution for PiMM, PiMS, and PiMZ phenotypes did not differ significantly by physician-confirmed diagnoses of emphysema, chronic bronchitis, or asthma. There was no statistically significant difference in mean FEV(1) slope values between PiMM, PiMS, and PiMZ phenotypes (-22.5, -21, and -7 mL per year, respectively). After controlling for smoking and other potential confounders, the FEV(1) slope was associated with an initial FEV(1) level and age for the initial questionnaire but not with the different phenotypes. Selecting cutoff values, we identified rapidly declining and nondeclining subgroups, based on the percent predicted changes in FEV(1). They also were not associated with alpha(1)-antitrypsin phenotypes. CONCLUSIONS: We conclude that the data from this longitudinal community study suggest that having the PiMZ phenotype is not a significant risk factor for an accelerated decline in FEV(1).

Asthma as a risk factor for COPD in a longitudinal study.

BACKGROUND: For several years, asthma and COPD have been regarded as distinct entities, with distinct clinical courses. However, despite distinctive physiologic features at the time of diagnosis, and different risk factors, the two diseases over time may develop features that are quite similar. STUDY OBJECTIVE: To evaluate the association between physician-diagnosed asthma and the subsequent development of COPD in a cohort of 3,099 adult subjects from Tucson, AZ. DESIGN AND METHODS: A prospective observational study. Participants completed up to 12 standard respiratory questionnaires and 11 spirometry lung function measurements over a period of 20 years. Survival curves (with time to development of COPD as the dependent variable) were compared between subjects with asthma and subjects without asthma at the initial survey. RESULTS: Subjects with active asthma (n = 192) had significantly higher hazard ratios than inactive (n = 156) or nonasthmatic subjects (n = 2751) for acquiring COPD. As compared with nonasthmatics, active asthmatics had a 10-times-higher risk for acquiring symptoms of chronic bronchitis (95% confidence interval [CI], 4.94 to 20.25), 17-times-higher risk of receiving a diagnosis of emphysema (95% CI, 8.31 to 34.83), and 12.5-times-higher risk of fulfilling COPD criteria (95% CI, 6.84 to 22.84), even after adjusting for smoking history and other potential confounders. CONCLUSIONS: Physician-diagnosed asthma is significantly associated with an increased risk for CB, emphysema, and COPD.

The relation of body mass index to asthma, chronic bronchitis, and emphysema.

BACKGROUND: Recent studies have suggested a relationship between asthma and obesity. Despite these reports, the effect of being underweight or overweight as a risk factor for airway obstructive diseases (AODs) is not clear. OBJECTIVES: To determine whether a relation of body mass index (BMI) to asthma, chronic bronchitis (CB), or emphysema exists (analysis 1), and, if so, whether the association between obesity and asthma is modified by gender (analysis 2). DESIGN: Nested case-control study from the longitudinal cohort of the Tucson Epidemiologic Study of Airways Obstructive Diseases. PATIENTS: Analysis 1: physician-confirmed incident cases of asthma (n = 102), CB (n = 299), or emphysema (n = 72) who denied any prior AODs. Analysis 2: all 169 incident cases of asthma, regardless of any previous AODs, stratified by gender and by other potential effect modifiers. In both analyses, we selected only subjects at least 20 years old who had weight and height measured during the study. MEASUREMENTS: BMI and other risk factors were assessed prior to the onset of the AOD (cases) or prior to the last completed survey (control subjects). RESULTS: A diagnosis of emphysema was significantly associated with a BMI < 18.5 (odds ratio [OR], 2.97; 95% confidence interval [CI], 1.33 to 6.68, when compared to healthy control subjects). A BMI >/= 28 increased the risk of receiving a diagnosis of asthma (OR, 2.10; 95% CI, 1.31 to 3.36) and CB (OR, 1.80; 95% CI, 1.32 to 2.46). About 30% of the patients with asthma and 25% of the patients with CB (vs 16% of the control subjects, p < 0.001) were preobese or obese, regardless whether BMI was assessed before the diagnosis or before the onset of respiratory symptoms. The relation of elevated BMI to asthma was significant only among women. CONCLUSIONS: Patients with emphysema are more likely to be underweight, and patients with CB are more likely to be obese. However, the temporal relationship between abnormal BMI and the onset of COPD is uncertain. Preobese and obese women are at increased risk of acquiring asthma. This relation, particularly if it is causal, has potentially relevant public health implications.

Rhinitis as an independent risk factor for adult-onset asthma.

BACKGROUND: For many years, the association between asthma and rhinitis has primarily been attributed to a common allergic background. Recently, it has been suggested that asthma and rhinitis are associated in the absence of atopy. The nature of this association is not well known. OBJECTIVE: The purpose of this study, which was performed in a large, longitudinal community population, was to determine the extent to which rhinitis is an independent risk factor for adult-onset asthma. METHODS: We carried out a nested case-control study from the longitudinal cohort of the Tucson Epidemiologic Study of Obstructive Lung Diseases. One hundred seventy-three incident patients with physician-confirmed asthma were compared with 2177 subjects who reported no asthma or shortness of breath with wheezing. Potential risk factors, including the presence of rhinitis, were assessed before the onset of asthma (patients) or before the last completed survey (control subjects). RESULTS: Rhinitis was a significant risk factor for asthma (crude odds ratio, 4.13; 95% confidence interval, 2.88-5.92). After adjustment for years of follow-up, age, sex, atopic status, smoking status, and presence of chronic obstructive pulmonary disease, the magnitude of the association was reduced but still highly significant (adjusted odds ratio, 3.21; 95% confidence interval, 2.19-4.71). After stratification, rhinitis increased the risk of development of asthma by about 3 times both among atopic and nonatopic patients and by more than 5 times among patients in the highest IgE tertile. Patients with rhinitis with persistent and severe nasal symptoms and a personal history of physician-confirmed sinusitis had an additional increased risk of asthma development. CONCLUSION: We conclude that rhinitis is a significant risk factor for adult-onset asthma in both atopic and nonatopic subjects. The nature of the association between rhinitis and asthma is open to interpretation.