Comparison of central and peripheral airway involvement before and during methacholine, mannitol and eucapnic hyperventilation challenges in mild asthmatics

Clin Respir J. 2011 Jan;5(1):10-8. doi: 10.1111/j.1752-699X.2009.00183.x.


Introduction: Testing for airway hyperresponsiveness with indirect stimuli as exercise or mannitol has been proposed to better reflect underlying airway inflammation, as compared with methacholine (MCh), believed to act directly on airway smooth muscle cells.

Objective: To investigate whether different direct and indirect stimuli induces different patterns of obstruction, recorded as central and peripheral resistance, and to see whether baseline resistance could predict a positive response to direct or indirect provocation.

Methods: Thirty-four mild asthmatics and 15 controls underwent MCh, mannitol and eucapnic voluntary hyperventilation (EVH) challenge tests. The response was evaluated with spirometry and impulse oscillometry (IOS).

Results: Twenty-three out of 34 asthmatics were positive to either EVH (22) or mannitol (13). Those positive to mannitol had a significant increased baseline value of IOS parameters such as ΔR5-R20 and AX. Twelve of the asthmatics had a 10% fall or more in forced expiratory volume in 1 s (FEV(1)) in all three challenge tests. However, the response pattern measured by IOS did not differ between the tests. When the limit for a positive mannitol provocation was set to 10% fall in FEV(1), 16 out of 19 mannitol-positive patients were also positive to EVH.

Conclusion: Even in mild asthmatics, a substantial number had a positive indirect test. Mannitol FEV(1) provocative dose to decrease FEV(1) by 10% from baseline (PD10) was closely associated to EVH10%. No difference in bronchoconstrictive pattern could be seen between the different provocation tests, but those positive to mannitol had more peripheral airway involvement at baseline. This supports the idea that peripheral airway involvement is an important predictor of asthma airway reactivity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aged
  • Asthma / diagnosis*
  • Asthma / physiopathology*
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests / methods*
  • Bronchoconstrictor Agents
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Mannitol / administration & dosage
  • Methacholine Chloride / administration & dosage
  • Middle Aged
  • Nitric Oxide / analysis
  • Oscillometry
  • Spirometry
  • Statistics, Nonparametric


  • Bronchoconstrictor Agents
  • Methacholine Chloride
  • Nitric Oxide
  • Mannitol