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

Abstract

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 metacholine of < 7.8 mumol, with a GM of 0.7 mumol (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 (SaO2) 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.

Evidence of mast cell activation and leukotriene release after mannitol inhalation

“…The FEV1 was used as the index of change in airway calibre (Microlab 3300 spirometer; Micro Medical, Kent, UK). A mannitol challenge was performed by progressively increasing the doses, as described previously [10]. Briefly, the dose protocol consisted of 0 (empty capsule acting as a placebo), 5,10,20,40,80,160,160 and 160 mg mannitol.…”

“…A positive response to mannitol identifies asthmatics with EIB [8,9] and there are no significant airway responses to mannitol in healthy nonasthmatics [10]. Inhaled mannitol is thought to cause airways to narrow in asthmatics by a similar mechanism to exercise, that is by increasing the osmolarity of the airway surface liquid [8].…”

Dry powder inhalation: past, present and future

“…On the application site, new dry powder bronchial challenge tests have recently been presented for methacholine and adenosine [110,166] in addition to the mannitol test [167].…”

Novel dry powder inhalation system based on dispersion of lyophilisates

“…Mannitol (Aridol ® , Pharmaxis Pharmaceuticals Limited), for example, is used in asthma diagnosis to identify persons with bronchial hyper-responsiveness [84]. For the bronchial provocation test patients are supposed to inhale the mannitol powder in increasing doses with the following protocol: 0 (empty capsule acting as a placebo), 5,10,20,40,80,160,160, and 160 mg mannitol whereby the 80-, and 160-mg doses are given in multiples of 40-mg capsules [85].…”