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.

SUMMARY Lung function was recorded in a cohort of 130 age specific children of low birth weight (under 2000 g) and a reference population of 120 unselected local schoolchildren at 7 years of age. Children of the cohort were similar in height and forced vital capacity to the reference group, but had significantly reduced forced expiratory volume in 0-75 second and expiratory flow indices. Although neonatal respiratory illness was associated with reduced airway function, we were unable to confirm that this was a consequence of oxygen treatment or mechanical ventilation. Low birth weight, however, was closely associated with poor airway function independent of neonatal respiratory illness. Other factors of importance included the male gender and maternal smoking. The reduction in airway function observed in the low birthweight children was associated with cough but not wheeze. The disparity between the relatively well preserved vital capacity and reduced airway function suggests that very low birth weight, and hence prematurity, has its greatest effect on the subsequent growth of airway function.

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Twenty-seven children of very low birthweight (less than or equal to 1,500 g) whose lung function had been measured on several occasions during the first year were studied at the age of about 9 years. Fifteen of the children had received neonatal intermittent positive pressure ventilation, mostly for respiratory distress syndrome. Ten of the ventilated children were still oxygen dependent at 30 days of age. Compared to the remainder of the group, mechanically ventilated children had reduced lung compliance in early infancy and increased thoracic gas volume in the middle of their first year. These changes correlated with the level of neonatal respiratory therapy as indicated by the oxygen score. Lung compliance in early infancy, but not thoracic gas volume, correlated with forced expiratory volume at 1 second recorded at 9 years. On the other hand, reduced airway conductance showed no significant correlation with the neonatal oxygen score, but there was a strong correlation between airway conductance late in infancy and lung function at 9 years. This relationship was independent of neonatal mechanical ventilation. We conclude that perinatal factors, which may be associated with disturbed lung mechanics early in infancy, are only weak and indirect predictors of childhood lung function. Airway conductance late in infancy, determined by constitutional factors, prematurity itself or other undetermined factors, is a good predictor of airway function at 9 years.