Methods for "indirect" challenge tests including exercise, eucapnic voluntary hyperpnea, and hypertonic aerosols

Clin Rev Allergy Immunol. 2003 Feb;24(1):27-54. doi: 10.1385/CRIAI:24:1:27.


Bronchial provocation tests that use stimuli that act indirectly to cause airway narrowing have a high specificity for identifying people with active asthma who have the potential to respond to treatment with antiinflammatory drugs. The first test to be developed was exercise and it was used to assess the efficacy of drugs such as sodium cromoglycate. Eucapnic voluntary hyperpnea was developed later, as a surrogate test for exercise. Hypertonic aerosols were introduced to mimic the dehydrating effects of evaporative water loss that occurs during hyperpnea. A wet aerosol of 4.5% saline or a dry powder formulation of mannitol is used. At present the indirect challenge tests are becoming increasingly recognised as appropriate for monitoring treatment with inhaled steroids. Indirect tests identify those with potential for exercise-induced bronchoconstriction, an important problem for some occupations, such as the defence forces, fire fighters and the police force and for some athletic activities. The advantage in using an indirect challenges, over a direct challenge with a single pharmacological agonist, is that a positive response indicates that inflammatory cells and their mediators (prostaglandins, leukotrienes and histamine) are present in the airways in sufficient numbers and concentration to indicate that asthma is active at the time of testing. The corollary to this is that a negative test in a known asthmatic indicates good control or mild disease. Another advantage is that healthy subjects do not have significant airway narrowing to indirect challenge tests. The protocols used for challenge with indirectly acting stimuli are presented in detail.

Publication types

  • Review

MeSH terms

  • Adult
  • Aerosols / administration & dosage
  • Asthma / diagnosis*
  • Asthma / prevention & control
  • Bronchial Provocation Tests*
  • Child
  • Child, Preschool
  • Clinical Protocols
  • Exercise Test* / instrumentation
  • Exercise Test* / methods
  • Forced Expiratory Flow Rates
  • Forced Expiratory Volume
  • Humans
  • Hypertonic Solutions / administration & dosage
  • Mannitol / administration & dosage
  • Sodium Chloride / administration & dosage
  • Spirometry


  • Aerosols
  • Hypertonic Solutions
  • Mannitol
  • Sodium Chloride