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Published ahead of print on April 17, 2008
Am. J. Respir. Crit. Care Med. 2008, doi:10.1164/rccm.200708-1174OC
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Submitted on August 9, 2007
Accepted on April 17, 2008

Airway Responsiveness in Mild to Moderate Childhood Asthma: Gender Influences on the Natural History

Kelan G Tantisira1*, Ryan Colvin2, James Tonascia2, Robert C Strunk3, Scott T Weiss4, Anne L Fuhlbrigge5, and Childhood Asthma Management Program Research Group6

1 Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Pumonary Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Center for Genomic Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 2 CAMP Coordinating Center, Bloomberg School of Public Health, John Hopkins University, Baltimore, MD, USA, 3 Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA, 4 Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Center for Genomic Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 5 Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Pumonary Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 6 Childhood Astma Management Program Research Group, none

* To whom correspondence should be addressed. 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 asthmatic children. Methods, Measurements, and Main Results: 1041 children initially aged 5-12 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. Least squares geometric mean models were fit to determine effects of gender and age on airway responsiveness (provocative concentration producing 20% decrease in FEV1 or 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. 7748 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. Post-pubertal girls had greater airway responsiveness, even after adjustment for FEV1 and other potential confounders. While multivariable regression analyses noted a variety of factors that influenced airway responsivness in both genders, a history of hayfever ({beta}= -0.30, p=0.005), respiratory allergy ({beta}= -0.32, p=0.006), or recent inhaled corticosteroid usage ({beta}= -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 post-pubertal asthmatic female than in males. While there are factors associated with airway responsiveness in both males and females, gender specific factors may contribute to new insights into asthma pathogenesis.
Key words: Methacholine, PC20, FEV1, bronchoconstriction, sex






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