Am. J. Respir. Crit. Care Med., Volume 156, Number 3, September 1997, 758-765

A New Method For Bronchial-provocation Testing in Asthmatic Subjects Using a Dry Powder of Mannitol

SANDRA D. ANDERSON, JOHN BRANNAN, JOANNE SPRING, NATASHA SPALDING, LEANNE T. RODWELL, KIM CHAN,^* IGOR GONDA,^* ANDREW WALSH,^* and ANDREW R. CLARK^*

Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown; and Department of Pharmacy, University of Sydney, Australia

We developed a bronchial provocation test (BPT) with a dry powder preparation of mannitol. The mannitol was inhaled from gelatin capsules containing 5, 10, 20, or 40 mg to a cumulative dose of 635 mg, and was delivered via an Inhalator, Halermatic, or Dinkihaler device. We studied the airway sensitivity to inhaled mannitol, the repeatability of the response, and the recovery after challenge in 43 asthmatic subjects 18 to 39 yr of age who had a 20% decrease in FEV₁ in response to inhaling a 4.5% NaCl. We compared this with the airway response to methacholine in 25 subjects. The geometric mean (GM) for the dose of dry mannitol required to reduce the FEV₁ by 15% of the baseline value (PD₁₅) was 64 mg, with a 95% confidence interval (CI) of 45 to 91. Subjects responsive to mannitol had a PD₂₀ to methacholine of < 7.8 µmol, with a GM of 0.7 µmol (CI: 0.4 to 1.2). For the first of two challenges to mannitol the PD₁₅ was 59 mg (CI: 36 to 97) and for the second the PD₁₅ was 58 mg (CI: 35 to 94) p = 0.91 (n = 23). Spontaneous recovery to within 5% of baseline occurred within 60 min and within 10 min after 0.5 mg terbutaline sulfate was inhaled. Arterial oxygen saturation (Sa_O2) remained at 93% or above during mannitol challenge. Subjects tolerated the inhalation of the mannitol well. A dry powder preparation of mannitol may be suitable to develop for bronchial provocation testing.

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