Published ahead of print on April 17, 2008, doi:10.1164/rccm.200708-1174OC
© 2008 American Thoracic Society doi: 10.1164/rccm.200708-1174OC
Airway Responsiveness in Mild to Moderate Childhood AsthmaSex Influences on the Natural History1 Channing Laboratory, 2 Pulmonary Division, and 3 Center for Genomic Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; 4 Childhood Asthma Management Program (CAMP) Coordinating Center, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and 5 Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri Correspondence and requests for reprints should be addressed to Kelan Tantisira, M.D., M.P.H., Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115. E-mail: kelan.tantisira{at}channing.harvard.edu Rationale: Airway responsiveness is a prognostic marker for asthma symptoms in later life. Objectives: To evaluate characteristics responsible for persistence of airway responsiveness in children with asthma. Methods: A total of 1,041 children, initially aged 5–12 years, with mild to moderate persistent asthma enrolled in the Childhood Asthma Management Program (CAMP) were studied prospectively for 8.6 ± 1.8 years with methacholine challenges yearly. Measurements and Main Results: Least squares geometric mean models were fit to determine effects of sex and age on airway responsiveness (provocative concentration producing 20% decrease in FEV1 [PC20]). Multiple linear regression analysis was performed to determine factors at baseline and over time, which were associated with PC20 at end of follow-up. A total of 7,748 methacholine challenges were analyzed. PC20 increased with age, with boys having greater increase after age 11 years than girls (P < 0.001). The divergence coincided with the mean age for Tanner stage 2. Postpubertal girls had greater airway responsiveness, even after adjustment for FEV1 and other potential confounders. Although multivariable regression analyses noted a variety of factors that influenced airway responsivness in both sexes, a history of hay fever (β= –0.30, P = 0.005), respiratory allergy (β= –0.32, P = 0.006), or recent inhaled corticosteroid usage (β= –0.18, P = 0.02) were associated with decrements in final log PC20 only in girls. Conclusions: Airway responsiveness (PC20) is more severe in the postpubertal female with asthma than in males. Although there are factors associated with airway responsiveness in both males and females, sex-specific factors may contribute to new insights into asthma pathogenesis.
Key Words: methacholine • PC20 • FEV1 • bronchoconstriction
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