Acute Bronchodilator Responsiveness to Tiotropium in Postinfectious Bronchiolitis Obliterans in Children

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Abstract

Background:

Patients with postinfectious bronchiolitis obliterans (PIBO) usually have severe airflow obstruction and respond poorly to β-adrenergic drugs. However, the bronchodilator response to an anticholinergic agent such as tiotropium bromide is not known. We studied the acute bronchodilator response to tiotropium for up to 24 h in children with PIBO using spirometric and plethysmographic criteria.

Methods:

A randomized, double-blind, placebo-controlled, crossover, prospective study was performed in patients with stable PIBO, 6 to 16 years of age. Standard spirometry and plethysmography were performed before and at 30, 60, 120, and 180 min and 24 h after inhalation of 18 μg of tiotropium or a placebo. After 7 to 14 days, the drugs were inverted, and the procedures were repeated. The changes in lung function parameters at each time point were compared with the baseline by analysis of variance and Tukey posttest, and the differences in all time points assessments vs baseline in tiotropium vs placebo groups were compared using the Friedman test.

Results:

A total of 30 patients were enrolled in the study (23 boys, seven girls; aged 10.9 ± 2.8 years) with baseline lung function values (% predicted) of FVC, FEV1, FEV1/FVC, forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), total lung capacity (TLC), residual volume (RV), RV/TLC, airway resistance (Raw), and specific airway conductance (sGaw) of 75 ± 15, 48 ± 14, 59 ± 11, 22 ± 11, 120 ± 19, 281 ± 101, 49 ± 13, 250 ± 65, and 23 ± 9, respectively. Statistically significant differences were observed after tiotropium inhalation in the following parameters compared with baseline: FVC at 60, 120, and 180 min and 24 h; FEV1 at 30, 60, 120, and 180 min; FEV1/FVC at 60, 120, and 180 min; FEF25%-75% at 60, 120, and 180 min; RV at 30, 60, 120, and 180 min; TLC at 30, 120, and 180 min; RV/TLC at 30, 60, 120, and 180 min; Raw at 30, 60, 120, and 180 min and 24 h; and sGaw at 30, 60, 120, and 180 min and 24 h. For the placebo group, no significant differences were observed in any lung function parameters at any time. The differences in the main functional measurements between the tiotropium and placebo groups were statistically significant.

Conclusions:

Tiotropium acutely decreased airway obstruction and air trapping for up to 24 h in children with PIBO.

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