Tolerability of the first inhaled mannitol dose in children with cystic fibrosis
V. V. Shadrina,
E. K. Zhekaite,
A. Yu. Voronkova,
V. D. Sherman,
Yu. A. Kondakova,
Yu. S. Pinegina,
A. A. Poloyko,
E. G. Furman,
E. I. Kondratyeva https://doi.org/10.18093/0869-0189-2024-34-4-515-521
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.
Supporting agencies: This article was prepared with the financial support of Pharmaxis Ltd.
About the Authors
V. V. Shadrina
State Budgetary Educational Institution of Higher Professional Training “Perm State Medical University named after Academician E.A. Wagner” of the Ministry of Healthcare of the Russian Federation; Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation
Russian Federation
Competing Interests:
Russian Federation
Vera V. Shadrina - Candidate of Medicine, Associate Professor, Department of Faculty and Hospital Pediatrics, State Budgetary Educational Institution of Higher Professional Training “Perm State Medical University named after Academician E.A. Wagner” of the Ministry of Healthcare of the Russian Federation; Leading Researcher, Scientific and Clinical Department of Cystic Fibrosis, Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation.
Petropavlovskaya ul. 26, Perm, 614990; Moskvorechye ul. 1, Moscow, 115522
Tel.: (342) 221-86-15
Competing Interests:
None
E. K. Zhekaite
Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; State Budgetary Healthcare Institution of the Moscow region “Research Clinical Institute of Childhood”, Healthcare Ministry of Moscow Region
Russian Federation
Competing Interests:
Russian Federation
Elena K. Zhekaite - Candidate of Medicine, Senior Researcher, Research and Clinical Department of Cystic Fibrosis, Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; Senior Researcher, Department of Hereditary and Metabolic Diseases, State Budgetary Healthcare Institution of the Moscow region “Research Clinical Institute of Childhood”, Healthcare Ministry of Moscow Region.
Moskvorechye ul. 1, Moscow, 115522; Kominterna ul. 124A, build. 1, Moskovskaya obl., Mytishchi, 141009
Tel.: (499) 324-15-01
Competing Interests:
None
A. Yu. Voronkova
Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; State Budgetary Healthcare Institution of the Moscow region “Research Clinical Institute of Childhood”, Healthcare Ministry of Moscow Region
Russian Federation
Competing Interests:
Russian Federation
Anna Yu. Voronkova - Candidate of Medicine, Leading Researcher, Scientific and Clinical Department of Cystic Fibrosis, Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; Senior Researcher, Department of Hereditary and Metabolic Diseases, State Budgetary Healthcare Institution of the Moscow region “Research Clinical Institute of Childhood”, Healthcare Ministry of Moscow Region.
Moskvorechye ul. 1, Moscow, 115522; Kominterna ul. 124A, build. 1, Moskovskaya obl., Mytishchi, 141009
Tel.: (499) 324-15-01
Competing Interests:
None
V. D. Sherman
Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation
Russian Federation
Competing Interests:
Russian Federation
Viktoriya D. Sherman - Candidate of Medicine, Leading Researcher, Research and Clinical Division of Cystic Fibrosis, Associate Professor, Department of Genetics of Respiratory System Diseases, Institute of Higher and Additional Professional Education, Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation.
Moskvorechye ul. 1, Moscow, 115522
Tel.: (499) 324-15-01
Competing Interests:
None
Yu. A. Kondakova
State budgetary healthcare institution of the Novosibirsk region “City Children’s Clinical Hospital of Emergency Medical Care”
Russian Federation
Competing Interests:
Russian Federation
Yulia A. Kondakova - Pulmonologist, Consultative and Diagnostic Center, State Budgetary Healthcare Institution of the Novosibirsk region “City Children’s Clinical Hospital of Emergency Medical Care”.
Krasnyy prospekt 3, Novosibirsk, 630007
Tel.: (383) 223-06-67
Competing Interests:
None
Yu. S. Pinegina
State Budgetary Healthcare Institution of the Novosibirsk region “State Novosibirsk Regional Clinical Hospital”
Russian Federation
Competing Interests:
Russian Federation
Yuliya S. Pinegina - Сandidate of Medicine, Chief Pediatric Pulmonologist of the Novosibirsk region, Head of the Pediatric Pulmonology Department, State Budgetary Healthcare Institution of the Novosibirsk region “State Novosibirsk Regional Clinical Hospital”.
NemirovichаDanchenko ul. 130, Novosibirsk, 630087
Tel.: (3832) 315-99-99
Competing Interests:
None
A. A. Poloyko
State budgetary healthcare institution of the Novosibirsk region “City Children’s Clinical Hospital of Emergency Medical Care”
Russian Federation
Competing Interests:
Russian Federation
Anastasia A. Poloyko - Pulmonologist, Consultative and Diagnostic Center, State Budgetary Healthcare Institution of the Novosibirsk region “City Children’s Clinical Hospital of Emergency Medical Care”.
Krasnyy prospekt 3, Novosibirsk, 630007
Tel.: (383) 223-06-67
Competing Interests:
None
E. G. Furman
State Budgetary Educational Institution of Higher Professional Training “Perm State Medical University named after Academician E.A.Wagner” of the Ministry of Healthcare of the Russian Federation
Russian Federation
Competing Interests:
Russian Federation
Evgeny G. Furman - Doctor of Medicine, Professor, Corresponding Member of Russian Academy of Sciences, Head of the Department of Faculty and Hospital Pediatrics, State Budgetary Educational Institution of Higher Professional Training “Perm State Medical University named after Academician E.A. Wagner” of the Ministry of Healthcare of the Russian Federation.
Petropavlovskaya ul. 26, Perm, 614990
Tel.: (342) 221-86-15
Competing Interests:
None
E. I. Kondratyeva
Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; State Budgetary Healthcare Institution of the Moscow region “Research Clinical Institute of Childhood”, Healthcare Ministry of Moscow Region
Russian Federation
Competing Interests:
Russian Federation
Elena I. Kondratyeva - Doctor of Medicine, Professor, Head of the Scientific and Clinical Department of Cystic Fibrosis, Head of the Department of Genetics of Respiratory System Diseases, Institute of Higher and Additional Professional Education, Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; Deputy Director for Research, State Budgetary Healthcare Institution of the Moscow region “Research Clinical Institute of Childhood”, Healthcare Ministry of Moscow Region.
Moskvorechye ul. 1, Moscow, 115522; Kominterna ul. 124A, build. 1, Moskovskaya obl., Mytishchi, 141009
Tel.: (495) 111-03-03
Competing Interests:
None
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Shadrina V.V., Zhekaite E.K., Voronkova A.Yu., Sherman V.D., Kondakova Yu.A., Pinegina Yu.S., Poloyko A.A., Furman E.G., Kondratyeva E.I. Tolerability of the first inhaled mannitol dose in children with cystic fibrosis. PULMONOLOGIYA. 2024;34(4):515-521. (In Russ.) https://doi.org/10.18093/0869-0189-2024-34-4-515-521
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