{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T03:06:51Z","timestamp":1770174411228,"version":"3.49.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Mucpharm Pty Ltd"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pulm Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    BromAc\n                    <jats:sup>\u00ae<\/jats:sup>\n                    (MP-171) is a novel first in class therapeutic agent under investigation for its potential in treating respiratory diseases. Evaluating its safety profile following inhalation is necessary for future clinical application. Here, we evaluated BromAc\n                    <jats:sup>\u00ae<\/jats:sup>\n                    safety in an extended subacute short-term inhalation study. Forty BALB\/c mice were divided into five groups (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20098 each): sham control, saline control, and three BromAc\n                    <jats:sup>\u00ae<\/jats:sup>\n                    dose groups at 0.250\/20, 0.500\/20, and 0.750\/20\u00a0mg\/mL. Treatments were administered by inhalation three times daily for 28 days. A final single dose was given on Day 29 before euthanasia. Various parameters were assessed during the study to evaluate the effect of BromAc such as wellbeing and bodyweight, along with tissue pathology and inflammatory cytokine assessment. The results indicated that inhalation of BromAc\n                    <jats:sup>\u00ae<\/jats:sup>\n                    over 28 days did not affect general health, behavior, or body weight compared to controls. No signs of respiratory distress, hemorrhage, hypoxia, or any other disorders were observed. Mild, non-dose-dependent lung pathology and inflammatory changes were observed across all groups including controls. There was no difference between treated and control groups on multiplex immunoassay. These findings suggest that BromAc\n                    <jats:sup>\u00ae<\/jats:sup>\n                    is safe for inhalation at the tested concentrations and exposure duration.\n                  <\/jats:p>","DOI":"10.1186\/s12890-025-04090-1","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T06:19:59Z","timestamp":1767680399000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical assessment of inhalational subacute safety of nebulized MP-171 (BromAc\u00ae)"],"prefix":"10.1186","volume":"26","author":[{"given":"Ahmed H.","family":"Mekkawy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md Khalilur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna","family":"Pillai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samina","family":"Badar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirela","family":"Simic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javed","family":"Akhter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah J.","family":"Valle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"issue":"8","key":"4090_CR1","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1111\/all.13139","volume":"72","author":"JL Aron","year":"2017","unstructured":"Aron JL, Akbari O. Regulatory T cells and type 2 innate lymphoid cell-dependent asthma. Allergy. 2017;72(8):1148\u201355.","journal-title":"Allergy"},{"key":"4090_CR2","doi-asserted-by":"crossref","unstructured":"Hlap\u010di\u0107 I, Belamari\u0107 D, Bosnar M, Kifer D, Vuki\u0107 Dugac A, Rumora L. Combination of Systemic Inflammatory Biomarkers in Assessment of Chronic Obstructive Pulmonary Disease: Diagnostic Performance and Identification of Networks and Clusters. Diagnostics (Basel). 2020;10(12):1029.","DOI":"10.3390\/diagnostics10121029"},{"key":"4090_CR3","doi-asserted-by":"publisher","first-page":"1201658","DOI":"10.3389\/fimmu.2023.1201658","volume":"14","author":"KL Raby","year":"2023","unstructured":"Raby KL, et al. Mechanisms of airway epithelial injury and abnormal repair in asthma and COPD. Front Immunol. 2023;14:1201658.","journal-title":"Front Immunol"},{"key":"4090_CR4","doi-asserted-by":"crossref","unstructured":"Hill DB, Long RF, Kissner WJ, Atieh E, Garbarine IC, Markovetz MR, Fontana NC, Christy M, Habibpour M, Tarran R, Forest MG, Boucher RC, Button B. Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH. Eur Respir J. 2018;52(6):1801297.","DOI":"10.1183\/13993003.01297-2018"},{"issue":"1","key":"4090_CR5","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1093\/oxfordjournals.bmb.a071454","volume":"34","author":"JM Creeth","year":"1978","unstructured":"Creeth JM. Constituents of mucus and their separation. Br Med Bull. 1978;34(1):17\u201324.","journal-title":"Br Med Bull"},{"issue":"47","key":"4090_CR6","doi-asserted-by":"publisher","first-page":"eabq5049","DOI":"10.1126\/sciadv.abq5049","volume":"8","author":"D Song","year":"2022","unstructured":"Song D, et al. MUC5B mobilizes and MUC5AC spatially aligns mucociliary transport on human airway epithelium. Sci Adv. 2022;8(47):eabq5049.","journal-title":"Sci Adv"},{"issue":"23","key":"4090_CR7","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1056\/NEJMra0910061","volume":"363","author":"JV Fahy","year":"2010","unstructured":"Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med. 2010;363(23):2233\u201347.","journal-title":"N Engl J Med"},{"issue":"8","key":"4090_CR8","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/j.rmed.2012.04.001","volume":"106","author":"A Yaghi","year":"2012","unstructured":"Yaghi A, et al. Ciliary beating is depressed in nasal cilia from chronic obstructive pulmonary disease subjects. Respir Med. 2012;106(8):1139\u201347.","journal-title":"Respir Med"},{"key":"4090_CR9","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1146\/annurev-physiol-021014-071931","volume":"77","author":"AE Tilley","year":"2015","unstructured":"Tilley AE, et al. Cilia dysfunction in lung disease. Annu Rev Physiol. 2015;77:379\u2013406.","journal-title":"Annu Rev Physiol"},{"issue":"9","key":"4090_CR10","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1007\/PL00000936","volume":"58","author":"HR Maurer","year":"2001","unstructured":"Maurer HR. Bromelain: biochemistry, Pharmacology and medical use. Cell Mol Life Sci. 2001;58(9):1234\u201345.","journal-title":"Cell Mol Life Sci"},{"issue":"5","key":"4090_CR11","first-page":"9","volume":"18","author":"ER Secor Jr","year":"2012","unstructured":"Secor ER Jr., et al. Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma. 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BMC Pulm Med. 2024;24(1):434.","journal-title":"BMC Pulm Med"},{"issue":"3","key":"4090_CR16","doi-asserted-by":"publisher","first-page":"425","DOI":"10.3390\/v13030425","volume":"13","author":"J Akhter","year":"2021","unstructured":"Akhter J, et al. The combination of Bromelain and acetylcysteine (BromAc) synergistically inactivates SARS-CoV-2. Viruses. 2021;13(3):425.","journal-title":"Viruses"},{"key":"4090_CR17","doi-asserted-by":"crossref","unstructured":"Coelho Dos Reis JGA, Ferreira GM, Louren\u00e7o AA, Ribeiro \u00c1L, da Mata CPDSM, de Melo Oliveira P, et al. Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19. Biomed Pharmacother. 2022;148:112753.","DOI":"10.1101\/2021.12.23.21268347"},{"issue":"2","key":"4090_CR18","doi-asserted-by":"publisher","first-page":"146","DOI":"10.3390\/arm91020013","volume":"91","author":"K Pillai","year":"2023","unstructured":"Pillai K, et al. Effect of nebulized bromac on rheology of artificial sputum: relevance to Muco-Obstructive respiratory diseases. Adv Respir Med. 2023;91(2):146\u201363.","journal-title":"Adv Respir Med"},{"issue":"9","key":"4090_CR19","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.3390\/life14091111","volume":"14","author":"N Valle","year":"2024","unstructured":"Valle N, et al. Impact of nebulized BromAc\u00ae on mucus plug clearance in a mechanically ventilated ex vivo ovine lung model of obstructive respiratory conditions. Life. 2024;14(9):1111.","journal-title":"Life"},{"issue":"1","key":"4090_CR20","doi-asserted-by":"publisher","first-page":"11882","DOI":"10.1038\/s41598-025-92242-y","volume":"15","author":"EVS Reis","year":"2025","unstructured":"Reis EVS, et al. Antiviral effect of Bromelain combined with acetylcysteine against SARS-CoV-2 Omicron variant. 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Eur Respir J 2025;66:Suppl. 69, PA3604.","DOI":"10.1183\/13993003.congress-2025.PA3604"}],"container-title":["BMC Pulmonary Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12890-025-04090-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12890-025-04090-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12890-025-04090-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T13:56:03Z","timestamp":1770126963000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12890-025-04090-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,6]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4090"],"URL":"https:\/\/doi.org\/10.1186\/s12890-025-04090-1","relation":{},"ISSN":["1471-2466"],"issn-type":[{"value":"1471-2466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,6]]},"assertion":[{"value":"20 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The safety study protocol was reviewed and approved by University of New South Wales (UNSW) Animal Care and Ethics Committee (ACEC), approval number iRECS6785.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Mucpharm Pty Ltd solely owns or has sublicensed the intellectual property surrounding BromAc\u00ae. D.L.M. and S.V. are shareholders of Mucpharm Pty Ltd. A.H.M., M.K.R., K.P., M.S., and J.A., are employees of Mucpharm Pty Ltd.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"49"}}