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Clinical Investigations: AIRWAYS |

Evaluation of Bronchial Constriction in Children With Cystic Fibrosis After Inhaling Two Different Preparations of Tobramycin*

Ghassan A. Alothman, MD; Muslim M. Alsaadi, MBBS; Bernard L. Ho, BSc, RCPT(P); Sharon L. Ho, BSc, RRT; Annie Dupuis, MSc; Mary Corey, PhD; Allan L. Coates, MD CM
Author and Funding Information

*From the Division of Respiratory Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Correspondence to: Allan L. Coates, MD CM, Division of Respiratory Medicine, Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada M5G IX8; e-mail: allan.coates@sickkids.ca



Chest. 2002;122(3):930-934. doi:10.1378/chest.122.3.930
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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 FEV1 (ΔFEV1) of 12 ± 9% (mean ± SD) for the IV preparation, compared to 4 ± 5% for the preservative-free preparation (p = 0.046). An ΔFEV1 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 ΔFEV1 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 ΔFEV1 > 10% after inhaling each preparation. The largest ΔFEV1 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.

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