Smoking Cessation and Lung Function in Mild-to-Moderate Chronic Obstructive Pulmonary Disease

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Abstract

Previous studies of lung function in relation to smoking cessation have not adequately quantified the long-term benefit of smoking cessation, nor established the predictive value of characteristics such as airway hyperresponsiveness. In a prospective randomized clinical trial at 10 North American medical centers, we studied 3, 926 smokers with mild-to-moderate airway obstruction (3,818 with analyzable results; mean age at entry, 48.5 yr; 36% women) randomized to one of two smoking cessation groups or to a nonintervention group. We measured lung function annually for 5 yr. Participants who stopped smoking experienced an improvement in FEV(1) in the year after quitting (an average of 47 ml or 2%). The subsequent rate of decline in FEV(1) among sustained quitters was half the rate among continuing smokers, 31 +/- 48 versus 62 +/- 55 ml (mean +/- SD), comparable to that of never-smokers. Predictors of change in lung function included responsiveness to beta-agonist, baseline FEV(1), methacholine reactivity, age, sex, race, and baseline smoking rate. Respiratory symptoms were not predictive of changes in lung function. Smokers with airflow obstruction benefit from quitting despite previous heavy smoking, advanced age, poor baseline lung function, or airway hyperresponsiveness.

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Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. The Lung Health Study Research Group.

Robert Wise, D Tashkin, Michael D Altose … (1996)

As part of a clinical trial of early intervention in chronic obstructive pulmonary disease (COPD) (the Lung Health Study), 5,733 smokers with mild to moderate airflow obstruction underwent methacholine challenge tests at baseline. All participants were randomized to receive either usual care (no intervention) or special intervention, consisting of intensive smoking cessation counseling and the prescription of a metered-dose inhaler containing either ipratropium bromide or placebo (two inhalations three times daily). For this report, we analyzed the relationship between baseline methacholine reactivity and subsequent change in lung function. Methacholine reactivity was expressed as a logarithmic function of the two-point slope of percent decline in FEV1 over the concentration of methacholine (LMCR). Using a random effects linear model, LMCR was found to be a strong predictor of change in FEV1% predicted, after controlling for baseline lung function, age, sex, baseline smoking history, and changes in smoking status. Significant interactions were found between reactivity and smoking behavior. In the first year, participants who quit smoking showed improvement in FEV1, whereas continuing smokers showed worsening, and between Years 1 and 5, lung function declined to a greater extent in continuing smokers than in sustained quitters. For both time periods, these quitter/smoker differences increased as a function of airway reactivity. These findings indicate that methacholine reactivity is an important predictor of progression of airway obstruction in continuing smokers with early COPD, independent of the baseline level of obstruct.

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Error in smoking measures: effects of intervention on relations of cotinine and carbon monoxide to self-reported smoking. The Lung Health Study Research Group.

H Voelker, Gary J Connett, Sarah Murray … (1993)

Sources of measurement error in assessing smoking status are examined. The Lung Health Study, a randomized trial in 10 clinical centers, includes 3923 participants in a smoking cessation program and 1964 usual care participants. Smoking at first annual follow-up was assessed by salivary cotinine, expired air carbon monoxide, and self-report. Each of these measures is known to contain some error. Sensitivity and specificity were calculated by comparing a biochemical measure with self-report to produce an undifferentiated estimate of error. Classification error rates due to imprecision of the biochemical measures and to the error in self-report were estimated separately. For cotinine compared with self-report, the sensitivity was 99.0% and the specificity 91.5%. For carbon monoxide compared with self-report, the sensitivity was 93.7% and the specificity 87.2%. The classification error attributed to self-report, estimated by comparing the results from intervention and control groups, was associated with the responses of 3% and 5% of participants, indicating a small but significant bias toward a socially desirable response. In absolute terms in these data, both types of error were small.

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The lung health study: airway responsiveness to inhaled methacholine in smokers with mild to moderate airflow limitation. The Lung Health Study Research Group.

D Tashkin, M D Altose, E Bleecker … (1992)

As part of a multicenter clinical trial (Lung Health Study), methacholine inhalation challenge testing was performed in 5,877 current cigarette smokers, ages 35 to 59 yr (mean 48.5 +/- 6.8 yr), with borderline to moderate airflow limitation (FEV1/FVC ratio 63.0 +/- 5.5). The test was successfully completed in 96.4% of subjects, of whom 63% were male and 95.9% were white. Symptomatic reactions to methacholine were rarely severe enough to require evaluation by a trial physician. Nonspecific airways hyperresponsiveness (AHR) was defined as a greater than or equal to 20% decline in FEV1 from the post-diluent control value after inhalation of less than or equal to 25 mg/ml methacholine. AHR was noted in a significantly higher percentage of women (85.1%) than men (58.9%). Moreover, nearly twice as many women as men (46.6 and 23.9%, respectively) responded to less than or equal to 5 mg/ml of methacholine. In both men and women, baseline degree of airways obstruction and clinical center were strongly associated with AHR (p less than 0.001), whereas age was not. Additional associations with AHR were analyzed in men and women separately using logistic regression after adjustment for baseline lung function, age, and center-to-center differences. In men, AHR was significantly related to symptoms of wheeze, chronic cough and/or sputum, and a history of asthma or hay fever (p less than 0.004), but not to current or lifetime tobacco use. By contrast, among women, AHR was not significantly associated with chronic cough and/or phlegm (p greater than 0.05) or a past history of asthma or hay fever (p greater than 0.1) and was only weakly related to wheeze and current asthma (p = 0.04), as well as to cigarette pack-years (p = 0.044). These results indicate that most continuing smokers with functional evidence of early chronic obstructive pulmonary disease have nonspecific AHR that is strongly related to gender and baseline lung function and, to a lesser extent, to respiratory symptoms. The reason for the striking effect of gender on AHR in early chronic obstructive pulmonary disease is unclear but cannot be attributed to male-female differences in age, cigarette use, presence of asthma, or baseline degree of airflow obstruction.