Carla Cristina Souza Gomez1, Paloma Lopes Francisco Parazzi2, Karl Jan Clinckspoor3, Renan Marrichi Mauch2, Francisco Benedito Teixeira Pessine3, Carlos Emilio Levy4, Andressa Oliveira Peixoto2, Maria Ângela Gonçalves Oliveira Ribeiro2, Antônio Fernando Ribeiro2, Douglas Conrad5, Paul Marquis Quinton6, Fernando Augusto Lima Marson7,8,9, José Dirceu Ribeiro10. 1. Center for Investigation in Pediatrics, Department of Pediatrics, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 126, Tessália Vieira de Camargo, Campinas, São Paulo, 13083-887, Brazil. carlacg.gomez@gmail.com. 2. Center for Investigation in Pediatrics, Department of Pediatrics, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 126, Tessália Vieira de Camargo, Campinas, São Paulo, 13083-887, Brazil. 3. Department of Physical Chemistry, Instituto de Química, Universidade Estadual de Campinas, 336, Josué de Castro, Campinas, São Paulo, 13083-970, Brazil. 4. Department of Clinical Pathology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 126, Tessália Vieira de Camargo, Campinas, São Paulo, 13083-887, Brazil. 5. Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego School of Medicine, 9500 Gilman Dr., La Jolla, CA, 92093-0830, USA. 6. Department of Pediatrics, University of California, San Diego School of Medicine, 9500 Gilman Dr, La Jolla, CA, 92093-0830, USA. 7. Center for Investigation in Pediatrics, Department of Pediatrics, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 126, Tessália Vieira de Camargo, Campinas, São Paulo, 13083-887, Brazil. fernandolimamarson@hotmail.com. 8. Department of Medical Genetics and Genomic Medicine, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 126, Tessália Vieira de Camargo, Campinas, São Paulo, 13083-887, Brazil. fernandolimamarson@hotmail.com. 9. Postgraduate Program in Health Science, Laboratory of Medical and Human Genetics, São Francisco University, Avenida São Francisco de Assis 218, Bragança Paulista, São Paulo, 12916-900, Brazil. fernandolimamarson@hotmail.com. 10. Center for Investigation in Pediatrics, Department of Pediatrics, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 126, Tessália Vieira de Camargo, Campinas, São Paulo, 13083-887, Brazil. jdirceuribeiro@gmail.com.
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.
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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