A PROSPECTIVE LONGITUDINAL-STUDY OF METHACHOLINE AIRWAY RESPONSIVENESS AS A PREDICTOR OF PULMONARY-FUNCTION DECLINE - THE NORMATIVE AGING STUDY
A PROSPECTIVE LONGITUDINAL-STUDY OF METHACHOLINE AIRWAY RESPONSIVENESS AS A PREDICTOR OF PULMONARY-FUNCTION DECLINE - THE NORMATIVE AGING STUDY
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DOI：
10.1164/ajrccm.152.1.7599868
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发表时间：
1995-07-01
影响因子：
24.7
通讯作者：
WEISS, ST
中科院分区：
文献类型：
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作者：
OCONNOR, GT;SPARROW, D;WEISS, ST
据推测，非特异性气道高反应性是一个危险因素，加速肺功能下降，在老龄化和慢性气流阻塞的发展。我们在一项前瞻性纵向研究中检验了这一假设，该研究纳入了912名参加规范性老龄化研究（NAS）的中年和老年男性（中位年龄60岁，范围41 - 86岁）。受试者在定期安排的NAS检查时接受乙酰甲胆碱激发试验和肺量测定，并在中位间隔3.3年后进行随访肺量测定。在初始检查时，还使用一组四种空气致敏原（混合草、混合树、豚草和屋尘）进行过敏皮肤试验。乙酰甲胆碱反应性表示为剂量-反应斜率（DRS）（即，连接醋甲胆碱剂量反应图起点与最后一点的直线的斜率），单位为FEV（1）/μ mol醋甲胆碱下降百分比。以肺功能下降率为结果变量，采用多元线性回归模型，研究乙酰甲胆碱DRS与随后肺功能年下降率（FEV（1）、FVC和FEV（1）/FVC）的关系。校正年龄、身高、吸烟状况和肺功能初始水平后，log（10）DRS是FEV（1）下降率的显著预测因子（回归系数β = 12.8，p = 0.03）和FEV（1）/FVC x 100（β = 0.506，p = 0.0001），是FVC的临界显著预测因子（β = 15.3，p = 0.05）。FEV（1）的回归模型预测与log（10）DRS增加2 SD相关的额外下降为8.4 ml/yr，而在同一模型中与当前吸烟相关的额外下降为17.2 ml/yr。在回归模型中调整特应性状态后，log（10）DRS与肺功能下降的关系对于FEV（1）/FVC x 100（β = 0.507，p = 0.0001）仍然显著，对于FEV（1）（P = 11.8，p = 0.05）和NC（P = 15.7，p 0.05）具有边缘显著性。限制对否认任何哮喘史的男性的分析削弱了FEV（1）下降的这种关系，但log（10）DRS仍然是FEV（1）/FVC年下降的重要预测因子。我们的结论是，气道反应性乙酰甲胆碱是一个显着的预测随后加速肺功能下降在这个队列的中年和老年男性。这一发现表明，需要进行干预试验，以确定降低非特异性气道反应性的治疗方法，如吸入性皮质类固醇，是否可以减缓慢性气流阻塞的进展，并防止致残性呼吸障碍的发展。
It has been hypothesized that nonspecific airway hyperresponsiveness is a risk factor for accelerated pulmonary-function decline during aging and the development of chronic airflow obstruction. We tested this hypothesis in a prospective, longitudinal study of 912 middle-aged and older men (median age, 60 yr; range, 41 to 86 yr) participating in the Normative Aging Study (NAS). Subjects underwent methacholine challenge testing and spirometry at the time of a regularly scheduled NAS examination, and follow-up spirometry was performed after a median interval of 3.3 yr. Allergy skin testing with a panel of four aeroallergens (mixed grasses, mixed trees, ragweed, and house dust) was also performed at the initial examination. Methacholine responsiveness was expressed as the dose-response slope (DRS) (i.e., the slope of a line connecting the origin with the last point of the methacholine dose-response plot) in units of percent decline FEV(1)/mu mol methacholine. The relationship of the methacholine DRS to the subsequent rate of annual decline in lung function (FEV(1), FVC, and FEV(1)/FVC) was examined using multiple linear-regression models with the rates of pulmonary-function decline as the outcome variables. After adjusting for age, height, smoking status, and initial level of lung function, the log(10) DRS was a significant predictor of the rate of decline of FEV(1) (regression coefficient beta = 12.8, p = 0.03) and FEV(1)/FVC x 100 (beta = 0.506, p = 0.0001), and a borderline significant predictor of FVC (beta = 15.3, p = 0.05). The regression model for FEV(1) predicted an excess decline of 8.4 ml/yr in association with a 2 SD increase in log(10) DRS, compared with an excess decline of 17.2 ml/yr in association with current cigarette smoking in the same model. After adjusting for atopic status in the regression models, the relationship of log(10) DRS to pulmonary-function decline remained significant for FEV(1)/FVC x 100 (beta = 0.507, p = 0.0001) and of borderline significance for FEV(1)(P = 11.8, p = 0.05) and NC (P = 15.7, p 0.05). Restricting the analysis to men who denied any history of asthma weakened this relationship for FEV(1) decline, but log(10) DRS remained a significant predictor of annual decline in FEV(1)/FVC. We conclude that airway responsiveness to methacholine was a significant predictor of subsequent accelerated pulmonary decline in pulmonary function in this cohort of middle-aged and older men. This finding suggests the need for intervention trials to determine whether therapies that reduce nonspecific airway responsiveness, such as inhaled corticosteroids, can slow the progression of chronic airflow obstruction and prevent the development of disabling ventilatory impairment.