Genetics of Airway Responsiveness and Lung Function
Lung Diseases, Obstructive
Chronic Obstructive Pulmonary Disease
|Study Start Date:||July 1997|
|Study Completion Date:||June 2002|
Airway responsiveness and lung function, endpoints with a strong genetic basis, are central to the obstructive airway diseases (asthma and COPD). In contrast, the dissection of the underlying genes requires unique sample resources, accurate and comprehensive phenotyping, and an efficient study design. To address to this three-pronged challenge, a genomic screen brought together a large, homogenous, mostly untreated sample from Anhui, China, a wealth of expertise in asthma phenotypes, and a potent study design based on extreme discordant sib pairs.
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.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005537
|Investigator:||Xiping Xu||Brigham and Women's Hospital|