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To evaluate the effects of randomly assigning smokers who have early chronic obstructive pulmonary disease (COPD) to a smoking-cessation intervention on the symptoms of chronic cough, chronic phlegm production, wheezing and shortness of breath, and to determine the effects of quitting smoking on these symptoms.A total of 5,887 male and female smokers 35 to 60 years of age with early COPD [defined as a forced expiratory volume in the first second (FEV1) of 55% to 90% of predicted and FEV1/forced vital capacity (FVC)0.70] were enrolled in a 5-year clinical trial. Two-thirds of participants were randomly assigned to smoking-intervention groups and one-third to a usual-care group. The intervention groups attended 12 intensive smoking-cessation sessions that included behavior modification techniques and the use of nicotine chewing gum. One intervention group was treated with ipratropium bromide by inhaler; the other intervention group received placebo inhalers. The usual-care group was advised to stop smoking. All participants were followed annually. Smoking status was biochemically validated by salivary cotinine measurements or exhaled carbon monoxide values.Validated 5-year sustained smoking cessation occurred in 22% of participants in the intervention compared with only 5% of participants in the usual-care group. At the end of the study, the prevalence of each of the four symptoms in the two intervention groups was significantly less than in the usual-care group (P0.0001). For example, among participants who did not report cough at baseline, 15% of those in the intervention groups had cough at least 3 months during the year, compared with 23% of those in usual care. Sustained quitters had the lowest prevalence of all four symptoms, whereas continuous smokers had the greatest prevalence of these symptoms. Changes in symptoms occurred primarily in the first year after smoking cessation. Respiratory symptoms were associated with greater declines in FEV1 during the study (P0.001). Ipratropium bromide had no long-term effects on respiratory symptoms.In this prospective randomized trial using an intention-to-treat analysis, smokers with early COPD who were assigned to a smoking-cessation intervention had fewer respiratory symptoms after 5 years of follow-up.

One hundred fifty subjects were enrolled in a long-term study of obstructive lung diseases; 84 of these were subjected to five or more spirometric studies over a period of two or more years. Stepdown regression analysis was performed to determine the association between many different variables and the annual rates of change in the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). The following associations were noted to be significant (p less than 0.03); more favorable rates of change of the FVC and FEV1 were associated with a higher alpha1-antitrypsin level and older age. Less favorable changes were associated with more years of cigarette smoking, more airway reactivity and more frequent lower respiratory tract illnesses.

Twenty-nine patients with chronic obstructive pulmonary disease (COPD), selected on the basis of their alpha 1 antitrypsin (AAT) phenotype or trypsin inhibitory capacity (TIC), were studied by clinical and physiologic methods. Six were homozygous, 10 were heterozygous and 13 were normal with respect to their AAT levels. Spirometry, lung volume and diffusing capacity measurements indicated that the extent of pulmonary disease was greater in the patients with homozygous AAT deficiency as compared to the other groups. Quantitative measurements of regional ventilation and perfusion were made using xenon 133 and the results were evaluated by statistical technics. Two different methods of discriminant analysis of the regional ventilation and perfusion data clearly showed the three groups of patients to be significantly different from each other. Since the heterozygous AAT deficient patients had a pattern of disease which distinguished them from patients with both severely deficient and normal AAT levels, it is concluded that heterozygosity for AAT is an important factor in the development of COPD.

In a study of chronic airflow limitation, we followed 140 subjects living in Utah at altitudes of 1,300 to 1,500 meters for seven to 13 years. Twelve-year survival probabilities were determined and compared with an age- and sex-matched Utah population. The lowest 12-year survival probability was 0.40 for those patients with a forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of less than or equal to 0.40, indicating that there is much variability in survival. Other indicators of a lower survival probability (and increased death risk ratio) were an FEV1 percent predicted less than or equal to 50, an FEV1 less than or equal to 1.5 liters, male gender, partial pressure of oxygen (PO2) [exercise] less than or equal to 50 mm Hg, partial pressure of carbon dioxide (PCO2) [rest] greater than 39 mm Hg, PCO2 (exercise) greater than 39 mm Hg, FVC percent predicted less than or equal to 80, PO2 (rest) less than or equal to 55 mm Hg, and a carbon monoxide diffusing capacity (DLCO) percent predicted less than or equal to 80. Current smokers had a poorer survival probability than the reference population and an increased death risk when compared with the nonsmokers in the study. Pack/years of smoking also affected survival. Other variables associated with reduced survival were a diagnosis of chronic bronchitis combined with emphysema, more rapid annual declines in the FEV1 and/or FVC, low alpha 1-antitrypsin levels, a 20 percent improvement in FEV1 following the use of a bronchodilator aerosol, and a lower socioeconomic class. Differences between these findings and those noted in other studies are in the main due to differences in the characteristics (such as age, diagnosis, and extent of disease) of the patients in the study populations. The findings have relevance in estimating a patient's prognosis and for developing guidelines for disability determination purposes.