A longitudinal evaluation of bronchial responsiveness to methacholine in children: role of baseline lung function, gender, and change in atopic status

Am J Respir Crit Care Med. 1996 Mar;153(3):1098-104. doi: 10.1164/ajrccm.153.3.8630551.


A longitudinal study was done to evaluate the determinants of bronchial responsiveness (BR) to methacholine in children and adolescents. A cohort of 892 7- to 11-yr-old schoolchildren was restudied after a 3.5-yr interval. The same protocol for methacholine challenge (up to 64.0 mg/ml) and skin prick testing was employed at both the baseline survey and follow-up. An overall decline in the level of BR was observed, the geometric mean slope (percent decline in FEV1 per mg/ml of methacholine) decreasing from 0.68 (95% CI=0.61 to 0.75) to 0.51 (95% CI=0.46 to 0.57) (p<0.001). At both surveys, the strongest determinants of slope were baseline pulmonary function level (FEF25-75) and degree of atopic status. After adjusting for log FEF25-75, no gender difference was found in the first survey, whereas girls had greater BR than boys at follow-up. Longitudinal changes in skin prick test reactivity were associated with the BR level. Subjects in whom an initially positive skin prick test became negative (5.3%) had an increased slope at baseline but a follow-up slope similar to that of never skin-reactors. Conversely, those whose skin prick test converted from negative to positive (13.0%) had a slope similar to that of never-reactors at baseline but became stronger responders to methacholine than never-reactors at follow-up. Finally, responsiveness was highest in the presence of persistently positive skin prick testing (13.5%). In conclusion, BR declines from childhood to adolescence, paralleling the increase in lung function during this period; the decline is less pronounced in females. Changes in atopic status are associated with modifications in the BR level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asthma / immunology
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests
  • Bronchoconstrictor Agents*
  • Child
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Humans
  • Hypersensitivity / immunology
  • Hypersensitivity / physiopathology*
  • Logistic Models
  • Longitudinal Studies
  • Lung / drug effects
  • Lung / physiopathology*
  • Male
  • Maximal Midexpiratory Flow Rate
  • Methacholine Chloride*
  • Multivariate Analysis
  • Sex Characteristics*
  • Skin Tests
  • Vital Capacity


  • Bronchoconstrictor Agents
  • Methacholine Chloride