No 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.

To determine predictors for failed reduction of inhaled corticosteroids (ICS), in 50 subjects with well-controlled asthma (age 43.7 [18-69]; 22 males) taking a median dose of 1,000 microg ICS/d (100-3,600 microg/d), ICS were halved every 8 wk. Airway hyperresponsiveness (AHR) to a bronchial provocation test (BPT) with histamine was measured at baseline. AHR to BPT with mannitol, spirometry, exhaled nitric oxide (eNO), and, in 31 subjects, sputum inflammatory cells were measured at baseline and at monthly intervals. Thirty-nine subjects suffered an asthma exacerbation. Seven subjects were successfully weaned off ICS. Using a Kaplan- Meier survival analysis, the significant predictors of a failure of ICS reduction were being hyperresponsive to both histamine and mannitol at baseline (p = 0.039), and being hyperresponsive to mannitol during the dose-reduction phase of the study (p = 0.02). Subjects older than 40 yr of age tended to be at greater risk of ICS reduction failure (p = 0.059). Response to mannitol and percentage sputum eosinophils were significantly greater before a failed ICS reduction than before the last successful ICS reduction, whereas there were no significant differences in symptoms, spirometry, or eNO. These findings suggest that documentation of patient's AHR or sputum eosinophils may be useful in guiding the reduction of ICS doses.