Safety, Tolerability, and Effects of Sodium Bicarbonate Inhalation in Cystic Fibrosis

Abstract

Background

Among the many consequences of loss of CFTR protein function, a significant reduction of the secretion of bicarbonate (HCO3) in cystic fibrosis (CF) is a major pathogenic feature. Loss of HCO3 leads to abnormally low pH and impaired mucus clearance in airways and other exocrine organs, which suggests that NaHCO3 inhalation may be a low-cost, easily accessible therapy for CF.

Objective

To evaluate the safety, tolerability, and effects of inhaled aerosols of NaHCO3 solutions (4.2% and 8.4%).

Methods

An experimental, prospective, open-label, pilot, clinical study was conducted with 12 CF volunteer participants over 18 years of age with bronchiectasis and pulmonary functions classified as mildly to severely depressed. Sputum rheology, pH, and microbiology were examined as well as spirometry, exercise performance, quality-of-life assessments, dyspnea, blood count, and venous blood gas levels.

Results

Sputum pH increased immediately after inhalation of NaHCO3 at each clinical visit and was inversely correlated with rheology when all parameters were evaluated: [G′ (elasticity of the mucus) = − 0.241; G″ (viscosity of the mucus) = − 0.287; G* (viscoelasticity of the mucus) = − 0.275]. G* and G′ were slightly correlated with peak flow, forced expiratory volume in 1 s (FEV1), and quality of life; G″ was correlated with quality of life; sputum pH was correlated with oxygen consumption (VO2) and vitality score in quality of life. No changes were observed in blood count, venous blood gas, respiratory rate, heart rate, peripheral oxygen saturation of hemoglobin (SpO2), body temperature, or incidence of dyspnea. No adverse events associated with the study were observed.

Conclusion

Nebulized NaHCO3 inhalation appears to be a safe and well tolerated potential therapeutic agent in the management of CF. Nebulized NaHCO3 inhalation temporarily elevates airway liquid pH and reduces sputum viscosity and viscoelasticity.

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Affiliations

Authors

Contributions

All authors approved the manuscript and agreed with its submission. CCSG formalized the protocol, collected patient data, wrote the manuscript, and responded to critical reviews of the study; FALM performed the statistical analysis of the data, wrote the manuscript, critically reviewed the study, and responded to critical reviews of the study; PFLP, KJC, RMM, FBTP, and MAGOR collected data; DC and PMQ provided the project concept and edited the manuscript; AOP, CEL, and AFR provided supervision and contributed to the safety analysis; JDR worked on supervision and the project concept, clinically evaluated the patients included in the study, and validated phenotypic findings according to repeatability criteria. All authors contributed to writing the manuscript.

Corresponding authors

Correspondence to Carla Cristina Souza Gomez or Fernando Augusto Lima Marson or José Dirceu Ribeiro.

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Funding

FALM and JDR Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for #2011/12939-4, #2011/18845-1, #2015/12183-8 and #2015/12858-5.

Conflicts of interest

The authors declare they have no conflicts of interest.

Ethical approval

All procedures in this study were in accordance with the 1964 Helsinki Declaration and its amendments. The project (#12398956) was approved by the research ethics committee of the Faculdade de Ciências Médicas, Universidade Estadual de Campinas.

Informed consent

Informed consent was obtained from each participant.

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Gomez, C.C.S., Parazzi, P.L.F., Clinckspoor, K.J. et al. Safety, Tolerability, and Effects of Sodium Bicarbonate Inhalation in Cystic Fibrosis. Clin Drug Investig 40, 105–117 (2020). https://doi.org/10.1007/s40261-019-00861-x

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