Tolerability of the first inhaled mannitol dose in children with cystic fibrosis

Abstract

Mannitol for inhalation is recommended for the treatment of cystic fibrosis in children over 6 years of age and adults. Because of the risk of bronchospasm, a challenge test to assess the drug tolerability should be performed prior to prescribing inhalation mannitol. Aim. Tо evaluate the tolerability of the first dose of inhaled mannitol in children with cystic fibrosis. Methods. The mannitol challenge test (according to the instructions for use of the Bronchitol (inhaled mannitol), Pharmaxis Ltd, Australia) was assessed in 81 children aged 6 to 18 years (11.6 ± 3.2 years). The patients were observed in the centers of the Novosibirsk region, the Moscow region, and the Perm region. The patient’s general state, forced expiratory volume in the first second (FEV1), and SpO2 were monitored. Results. Baseline FEV1 data in patients ranged from 30 % to 146 % (87.8 ± 25.7%), and SpO2 was 94 – 99% (97.7 ± 1.3%). 73 (90.1%) patients passed the test. In 8 (9.9%) patients, the following symptoms were observed: bronchospasm (6), laryngospasm (1), and vomiting (1). Bronchial obstruction was treated by inhalation of a bronchodilator, and the children were under observation until the restoration of FEV1. In patients who passed the test, FEV1 ranged from 33 to 149 % (85.4 ± 24.5%), and SpO2 spanned from 95 to 99% (96.7 ± 1.7%). The children who did not pass the test were monitored. One patient passed the test later when targeted therapy was added. Two children did not tolerate other mucolytic drugs (one child – NaCl solution in various dilutions, and the second patient suffering from asthma – dornase alfa). During follow-up, one patient was diagnosed with allergic bronchopulmonary aspergillosis at 12 years of age and with asthma at 13 years of age, which may have influenced the decrease in mannitol tolerability through formation of bronchial hyperreactivity. Thus, true adverse drug reaction in the form of bronchospasm occurred in three children out of 81 (3.7%). Conclusion. 90.1% of patients passed the inhalation mannitol challenge test, and 9.9% of patients did not pass the test. Analysis of adverse drug reactions revealed that only 3.7% of patients experienced true adverse reactions in the form of bronchospasm. During the test, patients were taught the correct technique for inhaling the drug. All the supplies to relieve bronchospasm should be readily available during the test.