Panhuysen C I, Bleecker E R, Koeter G H, Meyers D A, Postma D S
Department of Pulmonary Medicine, Beatrixoord Hospital, Haren, The Netherlands.
Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1734-42. doi: 10.1164/ajrccm.157.6.9606088.
To investigate the genetic susceptibility to asthma, we developed an algorithm to classify the phenotype of each family member enrolled in a family study on the genetics of asthma. This algorithm was applied to 92, two- and three-generation families, identified through a subject (proband) with asthma first diagnosed 25 yr previously. The algorithm consisted of five classes based on the presence or absence of bronchial hyperresponsiveness (BHR), respiratory symptoms, smoking, airways obstruction, and bronchodilator reversibility. All family members were classified as: (1) definite asthma; (2) probable asthma; (3) unclassifiable airway disease; (4) chronic obstructive pulmonary disease (COPD); (5) unaffected (without clinical evidence of asthma and COPD). Thirteen of the 92 probands (14%) could not be classified as asthmatic when retested 25 yr later because of loss of BHR, loss of bronchodilator reversibility, or a current history of cigarette smoking. Of the 265 first-degree offspring, 49 (18%) were classified as having definite asthma (Class 1), and 22 (8%) as probable asthma (Class 2). A large number of offspring with clinical evidence of asthma did not have a prior physician's diagnosis of asthma, and offspring in Class 1 (definite asthma), with and without a physician's diagnosis, had similar clinical and physiologic characteristics. These results support the usefulness of this approach to classify subjects with asthma for genetic epidemiologic studies and show that reliance on a prior physician's diagnosis may result in misclassification or underdiagnosis. Characterization of the offspring in this family study showed that there is familial clustering, which supports the presence of a hereditary component in asthma.
为了研究哮喘的遗传易感性，我们开发了一种算法，用于对参与哮喘遗传学家庭研究的每个家庭成员的表型进行分类。该算法应用于92个两代和三代家庭，这些家庭是通过一名25年前首次被诊断为哮喘的受试者（先证者）确定的。该算法基于支气管高反应性（BHR）、呼吸道症状、吸烟、气道阻塞和支气管扩张剂可逆性的有无分为五类。所有家庭成员被分类为：（1）确诊哮喘；（2）可能哮喘；（3）无法分类的气道疾病；（4）慢性阻塞性肺疾病（COPD）；（5）未受影响（无哮喘和COPD的临床证据）。92名先证者中有13名（14%）在25年后重新检测时，由于BHR丧失、支气管扩张剂可逆性丧失或目前有吸烟史，不能被分类为哮喘患者。在265名一级后代中，49名（18%）被分类为确诊哮喘（第1类），22名（8%）为可能哮喘（第2类）。大量有哮喘临床证据的后代之前没有医生诊断为哮喘，第1类（确诊哮喘）的后代，无论有无医生诊断，都有相似的临床和生理特征。这些结果支持了这种方法在哮喘遗传流行病学研究中对哮喘患者进行分类的有用性，并表明依赖先前医生的诊断可能导致错误分类或诊断不足。该家庭研究中后代的特征表明存在家族聚集性，这支持了哮喘中存在遗传成分。
