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

Abstract

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.

Area under the Maximum Expiratory Flow-Volume Curve – A Sensitive Parameter in the Evaluation of Airway Patency

“…The CF patients had chronic airway obstruction with viscous mucus secretion and a positive sweat test with increased chloride levels. CF patients were treated with mucolytics, antibiotics and physical therapy, and in some of the patients the efficacy of bronchodilators on airway obstruction has been proven [16, 17]. …”

"CF asthma": what is it and what do we do about it?

“…Although Cropp also concluded that combining them might be more beneficial, 51 a more recent study found that adding ipratropium to salbutamol gave no additional benefit. 53 There are theoretical concerns, however, that anticholinergic agents may further thicken the airway mucus in CF. 54 There is little evidence for the common practice of routine bronchodilation before physiotherapy, and the improvement in mucociliary clearance that has been shown in healthy subjects after inhaled β 2 agonists is much less convincing in patients with CF.…”

Treatment of Severe Small Airways Disease in Children with Cystic Fibrosis

“…[41] Conversely, Sanchez et al [42] demonstrated that in patients who responded, a combination of ipratropium bromide and a β 2 -agonist was superior to ipratropium alone. In a recent randomized, double-blind, placebo-controlled study, Ziebach et al [44] compared salbutamol with ipratropium bromide alone and in combination over a 4-day period. They found that salbutamol alone or in combination with ipratropium bromide was superior to ipratropium bromide alone; however, combining salbutamol with ipratropium bromide did not improve the efficacy of salbutamol on its own.…”