Efficacy of BREATHOX® Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH Study): A Randomized Pilot Clinical Trial

{ 'indexed': {'date-parts': [[2023, 9, 22]], 'date-time': '2023-09-22T05:09:40Z', 'timestamp': 1695359380985}, 'reference-count': 18, 'publisher': 'MDPI AG', 'issue': '18', 'license': [ { 'start': { 'date-parts': [[2023, 9, 20]], 'date-time': '2023-09-20T00:00:00Z', 'timestamp': 1695168000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [{'name': 'Liita Care'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>(1) Background: A high concentration of sodium chloride on in vitro cell culture ' 'leads to reduced SARS-CoV-2 replication. Therefore, our aim was to evaluate the effects of ' 'inhaling hypertonic NaCl particles (BREATHOX®) on the duration of COVID-19-induced acute ' 'symptoms. (2) Methods: A prospective, open label, randomized, standard of care-controlled ' 'group (SOC) pilot trial compared inhaled oral and nasal administered BREATHOX® (2.0 mg NaCl, ' 'particles size between 1–10 μm), with five or ten inhalations per day for ten days. The ' 'primary endpoint was the time to resolve COVID-19-related symptoms. Safety outcomes included ' 'adverse clinical and laboratory events. (3) Results: A total of 101 individuals were screened ' 'and 98 were randomly assigned to BREATHOX® ten sessions per day (Group 1; 33 patients), ' 'BREATHOX® five sessions per day (Group 2; 32 patients), or SOC (33 patients), and followed up ' 'for 28 days. There was an association with cough frequency after 10 days BREATHOX® compared ' 'to SOC [Group 1: hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.06–3.81; Group 2: HR ' '2.17, 95% CI 1.17–4.04]. No differences between the groups for the reported symptoms’ ' 'resolution time were seen after 28 days. After combining both BREATHOX® groups, the period to ' 'cough resolution 10 days after randomization was significantly lower than in SOC (HR 2.10, ' '95% CI 1.20–3.67). An adverse event occurred in 30% of Group 1, 36% of Group 2, and 9% in SOC ' 'individuals. One patient from SOC had a serious adverse event. Nasal burning, sore or itchy ' 'nose, and dry mouth were considered related to BREATHOX® use and resolved after stopping ' 'inhalations. (4) Conclusion: BREATHOX® inhalation is safe and may be effective in reducing ' 'the duration of COVID-19-induced coughing.</jats:p>', 'DOI': '10.3390/jcm12186075', 'type': 'journal-article', 'created': {'date-parts': [[2023, 9, 21]], 'date-time': '2023-09-21T02:38:45Z', 'timestamp': 1695263925000}, 'page': '6075', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Efficacy of BREATHOX® Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH ' 'Study): A Randomized Pilot Clinical Trial', 'prefix': '10.3390', 'volume': '12', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-2587-2759', 'authenticated-orcid': False, 'given': 'Suzana', 'family': 'Tanni', 'sequence': 'first', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Fernando', 'family': 'Wehrmeister', 'sequence': 'additional', 'affiliation': [ { 'name': 'Departament of Social Medicine, The Faculty of Medicine, Federal ' 'University of Pelotas, Avenida Duque de Caxias 250, Pelotas ' '96030-002, Rio Grande do Sul, Brazil'}]}, { 'given': 'Robson', 'family': 'Prudente', 'sequence': 'additional', 'affiliation': [ { 'name': 'Clinical Hospital of Botucatu Medical School, São Paulo State ' 'University (Unesp), Distrito de Rubião Junior s/n, Botucatu ' '18618-970, São Paulo, Brazil'}]}, { 'given': 'Felipe', 'family': 'Damatto', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Carlos', 'family': 'Breda Neto', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Leiliane', 'family': 'Oliveira', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Luana', 'family': 'Pagan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Mariana', 'family': 'Gatto', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Letícia', 'family': 'Vieira', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Liana', 'family': 'Coelho', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Diane', 'family': 'Rezende', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Luiz', 'family': 'Machado', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'ORCID': 'http://orcid.org/0000-0001-8103-3338', 'authenticated-orcid': False, 'given': 'Gustavo', 'family': 'Mota', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'ORCID': 'http://orcid.org/0000-0003-4060-870X', 'authenticated-orcid': False, 'given': 'Marina', 'family': 'Gaiato', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Felipe', 'family': 'Santaella', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'ORCID': 'http://orcid.org/0000-0002-8529-7637', 'authenticated-orcid': False, 'given': 'Elisângela', 'family': 'Campos', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'given': 'Estefânia', 'family': 'Franco', 'sequence': 'additional', 'affiliation': [ { 'name': 'Clinical Hospital of Botucatu Medical School, São Paulo State ' 'University (Unesp), Distrito de Rubião Junior s/n, Botucatu ' '18618-970, São Paulo, Brazil'}]}, { 'ORCID': 'http://orcid.org/0000-0001-9557-3968', 'authenticated-orcid': False, 'given': 'Matheus', 'family': 'Callegari', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'ORCID': 'http://orcid.org/0000-0001-7728-4505', 'authenticated-orcid': False, 'given': 'Marina Politi', 'family': 'Okoshi', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical School, São Paulo State University (Unesp), Distrito de ' 'Rubião Junior s/n, Botucatu 18618-970, São Paulo, Brazil'}]}, { 'ORCID': 'http://orcid.org/0000-0003-1975-3654', 'authenticated-orcid': False, 'given': 'Ulla', 'family': 'Weinreich', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Clinical Medicine, The Faculty of Medicine, ' 'Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, ' 'Denmark'}]}], 'member': '1968', 'published-online': {'date-parts': [[2023, 9, 20]]}, 'reference': [ { 'key': 'ref_1', 'unstructured': 'WHO (2020). WHO COVID-19 Dashboard, World Health Organization. Available ' 'online: https://covid19.who.int/.'}, { 'key': 'ref_2', 'doi-asserted-by': 'crossref', 'first-page': '363', 'DOI': '10.1038/s41577-020-0311-8', 'article-title': 'The trinity of COVID-19: Immunity, inflammation and intervention', 'volume': '20', 'author': 'Tay', 'year': '2020', 'journal-title': 'Nat. Rev. Immunol.'}, { 'key': 'ref_3', 'doi-asserted-by': 'crossref', 'first-page': '1708', 'DOI': '10.1056/NEJMoa2002032', 'article-title': 'Clinical Characteristics of Coronavirus Disease 2019 in China', 'volume': '382', 'author': 'Guan', 'year': '2020', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref_4', 'doi-asserted-by': 'crossref', 'first-page': '672', 'DOI': '10.21037/apm-21-25', 'article-title': 'The features comparison between patients in the ICU and general wards ' 'and between patients with different outcomes: A 2020 COVID-19 study', 'volume': '10', 'author': 'Chen', 'year': '2021', 'journal-title': 'Ann. Palliat. Med.'}, { 'key': 'ref_5', 'doi-asserted-by': 'crossref', 'first-page': 'P497', 'DOI': '10.1016/S0140-6736(20)30183-5', 'article-title': 'Clinical features of patients infected with 2019 novel coronavirus in ' 'Wuhan, China', 'volume': '395', 'author': 'Huang', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': 'ref_6', 'unstructured': 'COVID-19 Treatment Guidelines Panel (2023, April 22). Coronavirus ' 'Disease 2019 (COVID-19) Treatment Guidelines, Available online: ' 'https://www.covid19treatmentguidelines.nih.gov/.'}, { 'key': 'ref_7', 'first-page': 'e3352020', 'article-title': 'Mecanismos imunopatológicos envolvidos na infecção por SARS-CoV-2', 'volume': '56', 'author': 'Brito', 'year': '2020', 'journal-title': 'J. Bras. Patol. Med. Lab.'}, { 'key': 'ref_8', 'first-page': '4', 'article-title': 'A rapid advice guideline for the diagnosis and treatment of 2019 novel ' 'coronavirus (2019-nCoV) infected pneumonia (standard version)', 'volume': '7', 'author': 'Jin', 'year': '2020', 'journal-title': 'Mil. Med. Res.'}, { 'key': 'ref_9', 'doi-asserted-by': 'crossref', 'first-page': '102', 'DOI': '10.1016/j.jpha.2020.03.001', 'article-title': 'Molecular immune pathogenesis and diagnosis of COVID-19', 'volume': '10', 'author': 'Li', 'year': '2020', 'journal-title': 'J. Pharm. Anal.'}, { 'key': 'ref_10', 'first-page': '647', 'article-title': 'From SARS to COVID-19: Pathogens, receptor, pathogenesis and principles ' 'of the treatment', 'volume': '49', 'author': 'Wang', 'year': '2020', 'journal-title': 'Zhonghua Bing Li Xue Za Zhi'}, { 'key': 'ref_11', 'doi-asserted-by': 'crossref', 'first-page': '1514', 'DOI': '10.1021/acsptsci.1c00080', 'article-title': 'Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 ' 'Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial ' 'Cells', 'volume': '4', 'author': 'Machado', 'year': '2021', 'journal-title': 'ACS Pharmacol. Transl. Sci.'}, { 'key': 'ref_12', 'doi-asserted-by': 'crossref', 'first-page': '10446', 'DOI': '10.1021/acs.jpclett.0c02602', 'article-title': 'Molecular Dynamics Reveals Complex Compensatory Effects of Ionic ' 'Strength on the Severe Acute Respiratory Syndrome Coronavirus 2 ' 'Spike/Human Angiotensin-Converting Enzyme 2 Interaction', 'volume': '11', 'author': 'Rivera', 'year': '2020', 'journal-title': 'J. Phys. Chem. Lett.'}, { 'key': 'ref_13', 'unstructured': 'World Health Organization (2020). WHO R&D Blueprint Novel Coronavirus ' 'COVID-19 Therapeutic Trial Synopsis, World Health Organization.'}, { 'key': 'ref_14', 'doi-asserted-by': 'crossref', 'first-page': '1285', 'DOI': '10.1136/bmj.283.6302.1285', 'article-title': 'Bronchial hyperreactivity in response to inhalation of ultrasonically ' 'nebulised solutions of distilled water and saline', 'volume': '283', 'author': 'Schoeffei', 'year': '1981', 'journal-title': 'Br. Med. J.'}, { 'key': 'ref_15', 'first-page': 'CD001506', 'article-title': 'Nebulised hypertonic saline for cystic fibrosis', 'volume': '2018', 'author': 'Wark', 'year': '2018', 'journal-title': 'Cochrane Database Syst. Rev.'}, { 'key': 'ref_16', 'doi-asserted-by': 'crossref', 'first-page': '1810', 'DOI': '10.1164/ajrccm.164.10.2104024', 'article-title': 'Airway response to inhaled hypertonic saline in patients with moderate ' 'to severe chronic obstructive pulmonary disease', 'volume': '164', 'author': 'Taube', 'year': '2001', 'journal-title': 'Am. J. Respir. Crit. Care Med.'}, { 'key': 'ref_17', 'doi-asserted-by': 'crossref', 'first-page': '1116', 'DOI': '10.1034/j.1399-3003.2000.01522.x', 'article-title': 'Safety of sputum induction in chronic obstructive pulmonary disease', 'volume': '15', 'author': 'Lindqvist', 'year': '2000', 'journal-title': 'Eur. Respir. J.'}, { 'key': 'ref_18', 'unstructured': '(2023, April 22). COVID-19 Rapid Guideline: Managing COVID-19—The ' 'National Institute for Health and Care Excellence (NICE). 28.0 published ' 'on 29.03.2023. Available online: ' 'https://www.nice.org.uk/guidance/ng191.'}], 'container-title': 'Journal of Clinical Medicine', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.mdpi.com/2077-0383/12/18/6075/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 9, 21]], 'date-time': '2023-09-21T03:27:40Z', 'timestamp': 1695266860000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.mdpi.com/2077-0383/12/18/6075'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 9, 20]]}, 'references-count': 18, 'journal-issue': {'issue': '18', 'published-online': {'date-parts': [[2023, 9]]}}, 'alternative-id': ['jcm12186075'], 'URL': 'http://dx.doi.org/10.3390/jcm12186075', 'relation': {}, 'ISSN': ['2077-0383'], 'subject': ['General Medicine'], 'container-title-short': 'JCM', 'published': {'date-parts': [[2023, 9, 20]]}}