Evaluation of bronchial constriction in children with cystic fibrosis after inhaling two different preparations of tobramycin.

OBJECTIVES

This randomized, double-blind, cross-over study evaluated the risk of bronchoconstriction with two preparations of inhaled tobramycin in children with cystic fibrosis (CF) infected with Pseudomonas aeruginosa with and without airway hyperreactivity.

DESIGN

Of 19 children with CF (age range, 7 to 16 years) with mild-to-moderate pulmonary disease, 10 children were at high risk (HR) for bronchospasm (family history of asthma and previous response to bronchodilators) and 9 children were at low risk (LR) for bronchospasm (no family history of asthma or previous response to bronchodilators). Two solutions of tobramycin were administered: (1) 80 mg in a 2-mL vial diluted with 2 mL of saline solution containing the preservatives phenol and bisulfites (IV preparation); and (2) 300 mg in a preservative-free preparation in a 5-mL solution. Following a bronchodilator-free period of 12 h, the patients inhaled either one or the other preparation in random order on two different occasions, 2 weeks apart.

RESULTS

Prechallenge and postchallenge results for the LR group showed a percentage of fall in FEV(1) (DeltaFEV(1)) of 12 +/- 9% (mean +/- SD) for the IV preparation, compared to 4 +/- 5% for the preservative-free preparation (p = 0.046). An DeltaFEV(1) of > 10% was seen in six of nine patients for the IV preparation and in one of nine patients for preservative-free preparation. For the HR group, the DeltaFEV(1) was 17 +/- 13% for the IV-preparation group, compared to 16 +/- 12% for the preservative-free group (p = 0.4). In this group, equal numbers of patients (8 of 10 patients) had an DeltaFEV(1) > 10% after inhaling each preparation. The largest DeltaFEV(1) was 44% (HR group with the preservative-free preparation that forced the early termination of inhalation).

CONCLUSIONS

Both preparations caused significant bronchoconstriction in the HR group, and the preservative-containing IV preparation caused more bronchospasm in LR group than the preservative-free solution. Heightened airway reactivity in children with CF places them at risk of bronchospasm from inhalation therapy.