Application of an algorithm for the diagnosis of asthma in Chinese families - Limitations and alternatives for the phenotypic assessment of asthma infamily-based genetic studies

Phenotype assessment is a crucial issue in gene mapping studies of asthma. Recently, Panhuysen and coworkers proposed an algorithm to define the asthm a phenotype in gene mapping family-based studies. We classified members of 2,756 Chinese families ascertained on the basis of the presence of two or m ore siblings and no more than one parent with asthma using a slightly modif ied version of the aforementioned algorithm. Among 4,097 Chinese parents, 4 04 (9.9%) were classified as having "definite asthma," 284 (6.9%) as "proba ble asthma," 1,193 (29.1%) as "unclassifiable obstructive airway disease," 626 (15.3%) as "COPD," and 1,590 (38.8%) as "unaffected" (no obstructive ai rway disease). Among 6,424 Chinese offspring, 1,065 (16.6%) were classified as having "definite asthma," 820 (12.8%) as "probable asthma," 1,996 (31.1 %) as "unclassifiable obstructive airway disease," 228 (3.5%) as "COPD," an d 2,315 (36%) as "unaffected." The use of the algorithm proposed by Panhuys en and coworkers in a Chinese population with a high prevalence of smoking would result in the exclusion of subjects with asthma who smoke or who have severe airflow obstruction from linkage analysis, as well as in an inabili ty to explore any potential interactions between genetic factors and cigare tte smoking in the pathogenesis of asthma. In the absence of a "gold standa rd," definitions of asthma that incorporate a combination of respiratory sy mptoms, increased airway responsiveness or bronchodilator response, and a p hysician's diagnosis of asthma are reasonable. The choice of a particular d iagnostic algorithm for family-based genetic studies of asthma should be ma de according to factors such as the prevalence of smoking in the study popu lation. Genetic studies of intermediate phenotypes related to asthma, which are objectively defined and may be influenced by a smaller number of genes , continue to be of great importance.