Published ahead of print on June 3, 2005, doi:10.1164/rccm.200501-010OC Am. J. Respir. Crit. Care Med., Volume 172, Number 5, September 2005, 552-558 A more recent version of this article appeared on September 1, 2005
Submitted on January 4, 2005 Paternal History of Asthma and Airway Responsiveness in Children with AsthmaBenjamin A Raby1*,1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA, 2 Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA, 3 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA * To whom correspondence should be addressed. 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 asthmatic children participating in a randomized trial of anti-inflammatory medications (the Childhood Asthma Management Program [CAMP]). Methods: Methacholine challenge testing was performed prior to treatment randomization and once per year over an average of 4.5 years post-randomization. Crosssectional and longitudinal repeated measures analyses were performed to model the relationship between PC20 (the methacholine concentration causing a 20% fall in forced expiratory volume in one second) 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=.006). Although maternal history of asthma was not associated with AHR, children with two asthmatic parents had greater AHR than those with no asthmatic parents (median logePC20=0.52 vs. 1.17, p=.0008). Longitudinal multivariate analysis of the relation between paternal history of asthma and AHR using repeated PC20 measurements over 44 months post-randomization 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, family history, longitudinal analysis
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