Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group

Am J Respir Crit Care Med. 1999 Apr;159(4 Pt 1):1043-51. doi: 10.1164/ajrccm.159.4.9806052.


According to international guidelines, the level and adjustment of antiinflammatory treatment for asthma are based solely on symptoms and lung function. We investigated whether a treatment strategy aimed at reducing airway hyperresponsiveness (AHR strategy) in addition to the recommendations in the existing guidelines (reference strategy) led to: (1) more effective control of asthma; and (2) greater improvement of chronic airways inflammation. To accomplish this, we conducted a randomized, prospective, parallel trial involving 75 adults with mild to moderate asthma who visited a clinic every 3 mo for 2 yr. At each visit, FEV1 and AHR to methacholine were assessed, and subjects kept diaries of symptoms, beta2-agonist use, and peak expiratory flow (PEF). Medication with corticosteroids (four levels) was adjusted according to a stepwise approach (reference strategy), to which four severity classes of AHR were added (AHR strategy). At entry and after 2 yr, bronchial biopsies were obtained by fiberoptic bronchoscopy. Patients treated according to the AHR strategy had a 1.8-fold lower rate of mild exacerbations than did patients in the reference strategy group (0. 23 and 0.43 exacerbation/yr/patient, respectively). FEV1 also improved to a significantly greater extent in the AHR strategy group (p </= 0.05). In bronchial biopsies this was accompanied by a greater reduction in thickness of the subepithelial reticular layer in the AHR strategy group than in the reference strategy group (mean difference [95% confidence interval (CI): 1.7 micrometers (0.2 to 3.1) micrometers]). The changes in AHR in both strategy groups were correlated with eosinophil counts in the biopsies (r = -0.48, p = 0.003). We conclude that reducing AHR in conjunction with optimizing symptoms and lung function leads to more effective control of asthma while alleviating chronic airways inflammation. This implies a role for the monitoring of AHR or other surrogate markers of inflammation in the long-term management of asthma.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Administration, Topical
  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Asthma / drug therapy*
  • Asthma / pathology
  • Asthma / physiopathology
  • Biopsy
  • Bronchi / pathology*
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests
  • Bronchodilator Agents / administration & dosage
  • Female
  • Forced Expiratory Volume
  • Glucocorticoids
  • Humans
  • Inflammation
  • Male
  • Methacholine Chloride
  • Peak Expiratory Flow Rate
  • Practice Guidelines as Topic
  • Prospective Studies
  • Single-Blind Method
  • Steroids


  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Glucocorticoids
  • Steroids
  • Methacholine Chloride