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Published ahead of print on June 3, 2005, doi:10.1164/rccm.200501-010OC
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American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 552-558, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200501-010OC

Original Article

Paternal History of Asthma and Airway Responsiveness in Children with Asthma

Benjamin A. Raby, Kristel Van Steen, Juan C. Celedón, Augusto A. Litonjua, Christoph Lange, Scott T. Weiss for the CAMP Research Group*

Channing Laboratory, Department of Medicine, and Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital; Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center; Harvard Medical School; Department of Biostatistics, Harvard School of Public Health; and Harvard Partners Center for Genetics and Genomics, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Benjamin Raby, M.D.C.M., M.P.H., Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115. E-mail: benjamin.raby{at}channing.harvard.edu

Rationale: Little is known regarding the relationship between parental history of asthma and subsequent airway hyperresponsiveness (AHR) in children with asthma. Objectives: We evaluated this relationship in 1,041 children with asthma participating in a randomized trial of antiinflammatory medications (the Childhood Asthma Management Program [CAMP]). Methods: Methacholine challenge testing was performed before treatment randomization and once per year over an average of 4.5 years postrandomization. Cross-sectional and longitudinal repeated measures analyses were performed to model the relationship between PC20 (the methacholine concentration causing a 20% fall in FEV1) with maternal, paternal, and joint parental histories of asthma. Models were adjusted for potential confounders. Measurements and Main Results: At baseline, AHR was strongly associated with a paternal history of asthma. Children with a paternal history of asthma demonstrated significantly greater AHR than those without such history (median logePC20, 0.84 vs. 1.13; p = 0.006). Although maternal history of asthma was not associated with AHR, children with two parents with asthma had greater AHR than those with no parents with asthma (median logePC20, 0.52 vs. 1.17; p = 0.0008). Longitudinal multivariate analysis of the relation between paternal history of asthma and AHR using repeated PC20 measurements over 44 months postrandomization confirmed a significant association between paternal history of asthma and AHR among children in CAMP. Conclusions: Our findings suggest that the genetic contribution of the father is associated with AHR, an important determinant of disease severity among children with asthma.

Key Words: airway responsiveness • asthma • genetics • longitudinal analysis • parent of origin




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