Since this approach utilized an extant asthmatic family population, no support for data collection was required. The primary focus of the study was two intermediate phenotypes related to asthma and COPD: airway responsiveness (characterized by increased responsiveness to histamine methacholine or other nonspecific agonists and measured by the slope of the dose response relationship) and forced expiratory volume in 1 second (FEV1). Since both traits are continuous, the appropriate study design considered only siblings with extremely discordant phenotypes. For many studies, this strategy was not feasible due to the thousands of families that must be phenotyped to identify a sample of such siblings. The plan was to utilize the organization of a well-established network in China to collect 150 extreme discordant sib pairs of each intermediate phenotype. For airway responsiveness, the estimated power from this sample, equivalent to roughly 600 concordant sib pairs, was intended to surpass the power of all existing studies, including the U.S. Collaborative Study on the Genetics of Asthma. Further, with similar power, this was the first study to test for linkage to FEV1. Moreover, to further augment power, potential phenotypic heterogeneity was reduced by stratifying the analyses by total and specific serum IgE levels, skin test reactivity, peripheral blood eosinophilia, respiratory symptoms, age, gender, bronchodilator response, and cigarette smoking.