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The Protective Effect of Salbutamol Inhaled Using Different Devices on Methacholine Bronchoconstriction^*

^* From the Cardio-Thoracic Department, University of Pisa, Pisa, Italy.

Correspondence to: Daniele Giannini, MD, U.O. Fisiopatologia Respiratoria, Ospedale di Cisanello, via Paradisa 2, 56100 Pisa, Italy

Study objective: To determine the protective effect of salbutamol, 100 µg, inhaled by different devices (pressurized metered-dose inhaler [pMDI; Ventolin; GlaxoWellcome; Greenford, UK], pMDI + spacer [Volumatic; GlaxoWellcome], or breath-activated pMDI [Autohaler; 3M Pharmaceuticals; St. Paul, MN]) on bronchoconstriction induced by methacholine.

Design: Randomized, double-blind, cross-over, placebo-controlled study.

Patients: Eighteen subjects with stable, moderate asthma, asymptomatic, receiving regular treatment with salmeterol, 50 µg bid, and inhaled beclomethasone dipropionate, 250 µg bid, in the last 6 months, with high hyperreactivity to methacholine (baseline provocative dose of methacholine causing a 20% fall in FEV₁ [PD₂₀] geometric mean [GM], 0.071 mg). Subjects were classified into two groups: subjects with incorrect (n = 5) pMDI inhalation technique, and subjects with correct (n = 13) inhalation technique.

Methods and measurements: After cessation of therapy for 3 days, all subjects underwent four methacholine challenge tests, each test 1 week apart, each time 15 min after inhalation of salbutamol, 100 µg (via pMDI, pMDI + spacer, or Autohaler), or placebo. The protective effect on methacholine challenge test was evaluated as the change in the PD₂₀, and expressed in terms of doubling doses of methacholine in comparison with placebo treatment.

Results: The PD₂₀ was significantly higher after salbutamol inhalation than after placebo inhalation, but no significant difference was observed among the three different inhalation techniques. Only when salbutamol was inhaled via pMDI + spacer, PD₂₀ was slightly but not significantly higher (pMDI GM, 0.454 mg; pMDI + spacer GM, 0.559 mg; and Autohaler GM, 0.372 mg; not significant [NS]) than other inhalation techniques. Similar results (mean ±SEM) were obtained with doubling doses of methacholine (pMDI, 2 ± 0.47; pMDI + spacer, 3 ± 0.35; and Autohaler, 2.4 ± 0.40; NS). No significant difference was found among techniques when subjects with correct or incorrect inhalation technique were separately considered.

Conclusions: Our data show that the protective effect of salbutamol, 100 µg, on methacholine-induced bronchoconstriction is not affected by the different inhalation techniques, although inhalation via pMDI + spacer tends to improve the bronchoprotective ability of salbutamol. These data confirm the clinical efficacy of salbutamol, whatever the device, and the patient’s inhalation technique.

Key Words: inhalation devices • methacholine challenge test • salbutamol

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