Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients

Clin Exp Allergy. 2008 Jan;38(1):43-50. doi: 10.1111/j.1365-2222.2007.02878.x. Epub 2007 Nov 19.


Background: Airway hyperresponsiveness (AHR) to stimuli that cause bronchial smooth muscle (BSM) contraction indirectly through the release of endogenous mediators is thought to reflect airway inflammation more closely compared with AHR measured by stimuli that act directly on BSM.

Methods: Fifty-three adult non-smoking asthmatics (28 females, 18-56 years) who were not taking inhaled steroids were challenged with mannitol (up to 635 mg) and methacholine (up to 8 mumol). Induced sputum eosinophils, exhaled nitric oxide (eNO), peak flow variation and clinical severity of asthma according to the Global Initiative for Asthma guidelines were measured in addition to the health-related quality-of-life score using the Juniper asthma quality-of-life questionnaire.

Findings: Both AHR to mannitol as well as to methacholine was associated with elevated markers of airway inflammation: in 83% of asthma patients with AHR to mannitol, and in 88% of asthma patients with AHR to methacholine, the eNO level was >20 p.p.b. Sputum% eosinophils >1% was measured in 70% of asthma patients with AHR to mannitol and in 77% of asthma patients with AHR to methacholine. In asthma patients without AHR, 15% had an eNO level >20 p.p.b., but none had sputum% eosinophils >1%. AHR to mannitol was more closely associated with the percentage of sputum eosinophils (PD(15) to mannitol vs. sputum% eosinophils: r: -0.52, P<0.05), compared with AHR to methacholine (PD(20) to methacholine vs. sputum% eosinophils: r: -0.28, NS). Furthermore, there was a stronger correlation between AHR to mannitol and the level of eNO [PD(15) to mannitol vs. eNO (p.p.b.): r: -0.63, P<0.001], compared with AHR to methacholine [PD(20) to methacholine vs. eNO (p.p.b.): r: -0.43, P<0.05].

Interpretation: In asthma patients not being treated with steroids, AHR to mannitol and to methacholine indicated the presence of airway inflammation. AHR to mannitol reflected the degree of airway inflammation more closely when compared with methacholine.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / pathology
  • Biomarkers
  • Drug Therapy, Combination
  • Eosinophils / cytology
  • Female
  • Humans
  • Male
  • Mannitol / therapeutic use*
  • Methacholine Chloride / therapeutic use*
  • Middle Aged
  • Nitric Oxide / metabolism
  • Quality of Life
  • Sputum / cytology
  • Sputum / immunology


  • Biomarkers
  • Methacholine Chloride
  • Nitric Oxide
  • Mannitol