Carbocysteine as Adjuvant Therapy in Acute Respiratory Tract Infections in Patients without Underlying Chronic Conditions: Systematic Review and Meta-Analysis
Objective: This study aims to systematically examine the existing evidence
regarding the clinical benefits of carbocysteine as an adjunctive treatment in
acute bronchopulmonary and otorhinological processes. Design: Systematic
review and meta-analysis. Datasources: An electronic search was
conducted acrossPubMed,
Cochrane Library, clinicaltrials.gov, and the European Clinical Trial Register,
with the search dated to May 2023. Bibliographic references from other
literature reviews and meta-analyses were also reviewed. The search was limited
to randomized clinical trials published in any language and year. It was
completed by cross-checking the references of the located articles. Methods:
Inclusion criteria covered studies assessing systemic or inhaled carbocysteine,
regardless of dosing regimen. Concomitant medication use was acceptable if
balanced between intervention and control groups. Authors independently
extracted data, resolving disagreements through consensus. Methodological
quality assessment relied on critical reading of each study. Dichotomous
variables were analyzed using odds ratio (OR), and a final effect size was
calculated. Statistical significance was established when confidence intervals
did not cross the neutral value. Heterogeneity was assessed via the X2 test and I2 index. Results: Out of 318 initially identified
studies, 4 met inclusion criteria. The meta-analysis for poor general condition
yielded an OR of 0.45 in favor of intervention, p = 0.013, with non-significant
heterogeneity. Cough events showed a percentage of 15.8% for carbocysteine vs.
References
[1]
Mayor, S. (2010) Acute Respiratory Infections Are World’s Third Leading Cause of Death. British Medical Journal, 341, c630. https://doi.org/10.1136/bmj.c6360
[2]
Marimón, J.M. and Navarro-Marí, J.M. (2017) Métodos de diagnóstico rápido de las infecciones respiratorias. Enfermedades Infecciosas y Microbiología Clínica, 35, 108-115. https://doi.org/10.1016/j.eimc.2016.11.007
[3]
Bezerra, P., Britto, M., Correia, J., et al. (2011) Viral and Atypical Bacterial Detection in Acute Respiratory Infection in Children Under Five Years. PLOS ONE, 6, e18928. https://doi.org/10.1371/journal.pone.0018928
[4]
Teichtahl, H., Buckmaster, N. and Pertnikovs, E. (1997) The Incidence of Respiratory Tract Infection in Adults Requiring Hospitalization for Asthma. Chest, 112, 591-596. https://doi.org/10.1378/chest.112.3.591
[5]
Li, Y., Wang, X., Blau, D.M., et al. (2022) Global, Regional, and National Disease Burden Estimates of Acute Lower Respiratory Infections Due to Respiratory Syncytial Virus in Children Younger than 5 Years in 2019: A Systematic Analysis. The Lancet, 399, 2047-2064. https://doi.org/10.1016/S0140-6736(22)00478-0
[6]
Remartínez, S.G., Pión, M.G., Gómez, F.J.G. and García, E.G. (2015) Infecciones Respiratorias en Urgencias [Respiratoryinfections in Emergencies]. Medicine, 11, 5254-5263. https://doi.org/10.1016/j.med.2015.10.007
[7]
Anesi, G., Lynch, Y. and Evans, L. (2020) A Conceptual and Adaptable Approach to Hospital Preparedness for Acute Surge Events Due to Emerging Infectious Diseases. Critical Care Explorations, 24, e0110. https://doi.org/10.1097/CCE.0000000000000110
[8]
Nalbandian, A., Sehgal, K., Gupta, A., et al. (2021) Post-Acute COVID-19 Syndrome. Nature Medicine, 27, 601-615. https://doi.org/10.1038/s41591-021-01283-z
Bianco, A., Conte, S., Mariniello, D., et al. (2022) Mucolytic and Antioxidant Properties of Carbocysteine as a Strategy in COVID-19 Therapy. Life, 12, Article 1824. https://doi.org/10.3390/life12111824
[11]
Hoffmann, M., Kleine-Weber, H., Schroeder, S., et al. (2020) SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181, 271-280.E8. https://doi.org/10.1016/j.cell.2020.02.052
[12]
Hill, D.B., Button, B., Rubinstein, M., et al. (2022) Physiology and Pathophysiology of Human Airway Mucus. Physiological Reviews, 102, 1757-1836. https://doi.org/10.1152/physrev.00004.2021
[13]
Ikeuchi, Y., Kogiso, H., Hosogi, S., et al. (2019) Carbocysteine Stimulated an Increase in Ciliary Bend Angle via a Decrease in [Cl-]I in Mouse Airway Cilia. Pflügers Archiv—European Journal of Physiology, 471, 365-380. https://doi.org/10.1007/s00424-018-2212-2
[14]
Wu, G., Fang, Y., Yang, S., et al. (2004) Glutathione Metabolism and Its Implications for Health. The Journal of Nutrition, 134, 489-492. https://doi.org/10.1093/jn/134.3.489
[15]
Pace, E., Cerveri, I., Lacedonia, D., et al. (2022) Clinical Efficacy of Carbocysteine in COPD: Beyond the Mucolytic Action. Pharmaceutics, 14, Article 1261. https://doi.org/10.3390/pharmaceutics14061261
[16]
Asada, M., Yoshida, M., Hatachi, Y., et al. (2012) L-Carbocysteine Inhibits Respiratory Syncytial Virus Infection in Human Tracheal Epithelial Cells. Respir. Respiratory Physiology & Neurobiology, 180, 112-118. https://doi.org/10.1016/j.resp.2011.10.017
[17]
Kahraman, M.E., Yüksel, F. and Özbugday, Y. (2021) The Relationship between Covid-19 and Mucociliary Clearance. Acta Oto-Laryngologica, 141, 989-993. https://doi.org/10.1080/00016489.2021.1991592
[18]
Sun, L., Tang, L., Xu, Y., et al. (2010) The Effect and Mechanism of Action of Carbocysteine on Airway Bacterial Load in Rats Chronically Exposed to Cigarette Smoke. Respirology, 15, 1064-1071. https://doi.org/10.1111/j.1440-1843.2010.01816.x
[19]
Ndour, C.T., Ahmed, K., Nakagawa, T., et al. (2001) Modulating Effects of Mucoregulating Drugs on the Attachment of Haemophilus influenzae. Microbial Pathogenesis, 30, 121-127. https://doi.org/10.1006/mpat.2000.0417
[20]
Yasuda, H., Yamaya, M., Sasaki, T., et al. (2006) Carbocisteine Inhibits Rhinovirus Infection in Human Tracheal Epithelial Cells. European Respiratory Journal, 28, 51-58. https://doi.org/10.1183/09031936.06.00058505
[21]
Bonci, M. and Bozzi, A. (1994) Terapia mucoregolatricenella patología secernentedell’orecchio medio [Mucoregulatory Therapy in Secreting Disease of the Middle Ear]. Minerva Medica, 85, 83-87.
[22]
Malka, M. and Lablache, C.B. (1990) Interet d’un mucolytique, la carbocistèine, dans la bronchiteaiguë de l’enfant [Carbocysteine in the Treatment of Acute brOnchitis in Children]. Medicina Infantil, 97, 687-692.
[23]
Nakayama, Y., maeda, K., Fuanabashi, S., et al. (1977) Carbocisteine Syrup in Pediatrics: A Clinical Trial. Japanese Journal of Pediatrics, 10, 1823. (In Japanese)
[24]
Zanini, A. and Dodesni, G. (1974) Illisomucil in Campo Pediatrico [Lisomucilin Pediatrics]. Cliica Europea, 13, 1-12.
[25]
Rogers, D.F. (2007) Mucoactive Agents for Airway Mucus Hypersecretory Diseases. Respiratory Care, 52, 1176-1193.
[26]
Ishibashi, Y., Takayama, G., Inouye, Y. and Taniguchi, A. (2010) Carbocisteine Normalizes the Viscous Property of Mucus through Regulation of Fucosylated and Sialylated Sugar Chain on Airway Mucins. European Journal of Pharmacology, 641, 226-228. https://doi.org/10.1016/j.ejphar.2010.05.045
[27]
Dickey, B.F., Chen, J. and Peebles, R.S. (2022) Airway Mucus Dysfunction in COVID-19. American Journal of Respiratory and Critical Care Medicine, 206, 1304-1306. https://doi.org/10.1164/rccm.202207-1306ED
[28]
Takafumi, K., Takanori, A. and Caitlin, E. (2022) Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease. American Journal of Respiratory and Critical Care Medicine, 206, 1336-1352. https://doi.org/10.1164/rccm.202111-2606OC
