Airway responsiveness in mild to moderate childhood asthma: sex influences on the natural history

Am J Respir Crit Care Med. 2008 Aug 15;178(4):325-31. doi: 10.1164/rccm.200708-1174OC. Epub 2008 Apr 17.


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 FEV(1) [PC(20)]). Multiple linear regression analysis was performed to determine factors at baseline and over time, which were associated with PC(20) at end of follow-up. A total of 7,748 methacholine challenges were analyzed. PC(20) 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 FEV(1) 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 (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 PC(20) only in girls.

Conclusions: Airway responsiveness (PC(20)) 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Age Factors
  • Anti-Asthmatic Agents / administration & dosage
  • Asthma / epidemiology*
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / epidemiology*
  • Bronchial Hyperreactivity / physiopathology
  • Bronchial Provocation Tests
  • Bronchoconstriction / physiology
  • Bronchodilator Agents / administration & dosage
  • Budesonide / administration & dosage
  • Child
  • Child, Preschool
  • Cohort Studies
  • Disease Progression
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume / drug effects
  • Forced Expiratory Volume / physiology
  • Humans
  • Least-Squares Analysis
  • Male
  • Methacholine Chloride
  • Nedocromil / administration & dosage
  • Prognosis
  • Prospective Studies
  • Puberty / physiology
  • Sex Ratio
  • Vital Capacity / drug effects
  • Vital Capacity / physiology


  • Anti-Asthmatic Agents
  • Bronchodilator Agents
  • Nedocromil
  • Methacholine Chloride
  • Budesonide