Bronchodilatory effects of salbutamol, ipratropium bromide, and their combination: double-blind, placebo-controlled crossover study in cystic fibrosis

Pediatr Pulmonol. 2001 Jun;31(6):431-5. doi: 10.1002/ppul.1071.


The efficacy of inhaled sympathomimetic and anticholinergic agents on airway obstruction in cystic fibrosis (CF) has been proven in several studies. However, studies comparing combined therapy with monotherapy led to divergent results, probably due to different study designs, different dosages, and the small numbers of patients investigated. Therefore, we wanted to answer the question which inhalation has the best short term effect: a sympathomimetic or an anticholinergic agent, or the combination of both. We investigated 17 patients with CF on 4 successive days in the morning, using pulmonary function testing before and 30 min after inhalation. Each patient received aerosolized salbutamol (SB, maximum dose (max.) 2.5 mg), ipratropium bromide (IB, max. 0.5 mg), the combination of both, or placebo (normal saline) in a randomized, double-blind crossover design. The mean forced expiratory volume in the first second improved significantly (adjusted P-value < 0.017) after each treatment compared to placebo. Analysis of variance showed that SB and combination therapy with SB and IB were superior to IB alone, without significant difference between SB and combination therapy. Response of a patient to combined therapy was usually associated with response to SB. Long-term efficacy and side effects of treatment with bronchodilators still remain to be investigated after this short term study. We conclude that in CF patients bronchodilator therapy with sympathomimetic agents is usually sufficient. Only in cases with proven additional benefit from inhalation by anticholinergics should combination therapy be recommended.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Aerosols
  • Airway Obstruction / drug therapy
  • Airway Obstruction / etiology
  • Albuterol / administration & dosage*
  • Albuterol / pharmacology*
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / pharmacology*
  • Child
  • Cross-Over Studies
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / pathology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Ipratropium / administration & dosage*
  • Ipratropium / pharmacology*
  • Male
  • Placebos
  • Respiratory Function Tests
  • Treatment Outcome


  • Aerosols
  • Bronchodilator Agents
  • Placebos
  • Ipratropium
  • Albuterol