Kesten S, Dzyngel B, Chapman K R, Zamel N, Tarlo S, Malo J L, Slutsky A S
University of Toronto, Canada.
J Asthma. 1997;34(6):483-91. doi: 10.3109/02770909709055392.
In 1991, we began a project to search for the genetic basis of asthma using linkage analysis. We encountered discord between a history of asthma and physiological measures of variable airflow obstruction and sought to examine the frequency of such occurrences and the issues surrounding phenotyping of patients with asthma. We reviewed our experience in ascertaining the asthma phenotype in 50 nuclear families comprised of 219 subjects (110 male, 109 female). Three respiratory physicians reviewed data including a questionnaire, skin testing, objective measures of variable airflow obstruction [increase in FEV1 > or = 15% following salbutamol 400 micrograms of PC20 (methacholine) < or = 4 mg/ml], and serum for IgE. Thirty-eight percent of subjects had both objective and questionnaire data consistent with asthma (++) whereas 39% had negative objective and negative questionnaire findings (--) (i.e., no asthma). A positive history but negative objective findings occurred in 7% of subjects, 2% had a negative history and positive objective findings. Retesting was requested in 13% of subjects; review of historical data was requested in 1% (i.e., childhood asthma but no present asthma). Retesting was requested for either (a) positive history, negative objective if symptoms were seasonal or the subject was using medications known to affect the challenge study, (b) viral infection within 6 weeks of a positive methacholine study, or (c) technically inadequate study. Overall, after the initial assessment, all members of only 22 families could be catagorized as either ++ or --. The diagnostic group requested at least 1 retest in 19 families and a review of historical records in 2 families. We conclude that discordance between self-reported questionnaire data and laboratory measures of variable airflow limitation is common and will increase the numbers of asthmatic subjects in studies that seek to determine the genetic basis of asthma.
1991年，我们启动了一个项目，运用连锁分析探寻哮喘的遗传基础。我们发现哮喘病史与可变气流阻塞的生理学指标之间存在不一致的情况，并试图研究此类情况的发生频率以及哮喘患者表型分型所涉及的问题。我们回顾了在确定由219名受试者（110名男性，109名女性）组成的50个核心家庭中哮喘表型时的经验。三位呼吸内科医生审查了相关数据，包括一份问卷、皮肤测试、可变气流阻塞的客观指标[沙丁胺醇400微克后FEV1增加≥15%或PC20（乙酰甲胆碱）≤4毫克/毫升]以及血清IgE。38%的受试者客观指标和问卷数据均与哮喘相符（++），而39%的受试者客观指标和问卷结果均为阴性（--）（即无哮喘）。7%的受试者有阳性病史但客观指标为阴性，2%的受试者有阴性病史但客观指标为阳性。13%的受试者被要求重新测试；1%的受试者被要求查阅历史数据（即儿童期哮喘但目前无哮喘）。若出现以下情况则要求重新测试：（a）病史阳性但客观指标阴性，前提是症状为季节性或受试者正在使用已知会影响激发试验的药物；（b）乙酰甲胆碱激发试验阳性后6周内发生病毒感染；或（c）技术上不充分的试验。总体而言，在初始评估后，只有22个家庭的所有成员能够被归类为++或--。诊断小组要求19个家庭至少进行1次重新测试，2个家庭查阅历史记录。我们得出结论，自我报告的问卷数据与可变气流受限的实验室测量结果之间的不一致情况很常见，这会增加旨在确定哮喘遗传基础的研究中哮喘受试者的数量。
