Tashkin D P, Altose M D, Bleecker E R, Connett J E, Kanner R E, Lee W W, Wise R
Pulmonary & Critical Care, UCLA School of Medicine 90024-1690.
Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):301-10. doi: 10.1164/ajrccm/145.2_Pt_1.301.
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.
作为一项多中心临床试验（肺部健康研究）的一部分，对5877名年龄在35至59岁（平均48.5±6.8岁）、气流受限处于临界至中度（FEV1/FVC比值为63.0±5.5）的现吸烟者进行了乙酰甲胆碱吸入激发试验。96.4%的受试者成功完成了该试验，其中63%为男性，95.9%为白人。对乙酰甲胆碱的症状反应很少严重到需要试验医生进行评估。非特异性气道高反应性（AHR）定义为吸入小于或等于25mg/ml乙酰甲胆碱后FEV1较稀释后对照值下降大于或等于20%。女性中出现AHR的比例（85.1%）显著高于男性（58.9%）。此外，对小于或等于5mg/ml乙酰甲胆碱有反应的女性人数几乎是男性的两倍（分别为46.6%和23.9%）。在男性和女性中，气道阻塞的基线程度和临床中心与AHR密切相关（p<0.001），而年龄则不然。在对基线肺功能、年龄和中心间差异进行调整后，分别使用逻辑回归对男性和女性中与AHR的其他关联进行了分析。在男性中，AHR与喘息、慢性咳嗽和/或咳痰症状以及哮喘或花粉症病史显著相关（p<0.004），但与当前或终生吸烟情况无关。相比之下，在女性中，AHR与慢性咳嗽和/或咳痰（p>0.05）或既往哮喘或花粉症病史（p>0.1）无显著关联，仅与喘息和当前哮喘（p = 0.04）以及吸烟包年数（p = 0.044）有微弱关联。这些结果表明，大多数有早期慢性阻塞性肺疾病功能证据的持续吸烟者具有非特异性AHR，其与性别和基线肺功能密切相关，在较小程度上与呼吸道症状相关。早期慢性阻塞性肺疾病中性别对AHR产生显著影响的原因尚不清楚，但不能归因于男女在年龄、吸烟、哮喘存在情况或气流阻塞基线程度方面的差异。
