Tashkin D P, Altose M D, Connett J E, Kanner R E, Lee W W, Wise R A
UCLA School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1690, USA.
Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1802-11. doi: 10.1164/ajrccm.153.6.8665038.
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.
作为慢性阻塞性肺疾病（COPD）早期干预临床试验（肺部健康研究）的一部分，5733名患有轻度至中度气流受限的吸烟者在基线时接受了乙酰甲胆碱激发试验。所有参与者被随机分配接受常规护理（无干预）或特殊干预，特殊干预包括强化戒烟咨询以及开具含有异丙托溴铵或安慰剂的定量吸入器处方（每日三次，每次两喷）。在本报告中，我们分析了基线乙酰甲胆碱反应性与随后肺功能变化之间的关系。乙酰甲胆碱反应性表示为FEV1下降百分比相对于乙酰甲胆碱浓度的两点斜率的对数函数（LMCR）。使用随机效应线性模型，在控制了基线肺功能、年龄、性别、基线吸烟史和吸烟状态变化后，发现LMCR是预测预计FEV1%变化的有力指标。在反应性与吸烟行为之间发现了显著的相互作用。在第一年，戒烟者的FEV1有所改善，而持续吸烟者的FEV1则恶化，并且在第1年至第5年期间，持续吸烟者的肺功能下降程度比持续戒烟者更大。在这两个时间段内，这些戒烟者/吸烟者的差异都随着气道反应性的增加而增大。这些发现表明，乙酰甲胆碱反应性是早期COPD持续吸烟者气道阻塞进展的重要预测指标，与阻塞的基线水平无关。
