PT - JOURNAL ARTICLE AU - Philipp Kolb AU - Chandak Upagupta AU - Megan Vierhout AU - Ehab Ayaub AU - Pierre Simon Bellaye AU - Jack Gauldie AU - Chiko Shimbori AU - Mark Inman AU - Kjetil Ask AU - Martin R.J. Kolb TI - The importance of interventional timing in the bleomycin model of pulmonary fibrosis AID - 10.1183/13993003.01105-2019 DP - 2020 Jan 01 TA - European Respiratory Journal PG - 1901105 4099 - http://erj.ersjournals.com/content/early/2020/03/04/13993003.01105-2019.short 4100 - http://erj.ersjournals.com/content/early/2020/03/04/13993003.01105-2019.full AB - Idiopathic Pulmonary Fibrosis (IPF) is a complex disease of unknown etiology which makes drug development challenging. Single administration of bleomycin directly to the lungs of mice is a widely used experimental model for studying pulmonary fibrogenesis and to evaluate the effect of therapeutic anti-fibrotic strategies. The model works by inducing an early inflammatory phase which transitions into fibrosis after 5–7 days. This initial inflammation makes therapeutic timing crucial. To accurately assess anti-fibrotic efficacy, the intervention should inhibit fibrosis without impacting early inflammation.Studies published between 2008 and 2019 using the bleomycin model to investigate pulmonary fibrosis were retrieved from PubMed, and study characteristics were analysed. Intervention based studies were classified as either preventative (starting <7 days after bleomycin installation) or therapeutic (>7 days). Studies were also cross-referenced with current major clinical trials to assess the availability of preclinical rational.A total of 976 publications were evaluated. 726 investigated potential therapies, of which 443 (61.0%) were preventative alone, 166 (22.9%) therapeutic alone, and 105 (14.5%) were both. Of the 443 preventative studies, only 70 (15.8%) characterised inflammation during the model's early inflammatory phase. Of the reported 145 IPF clinical trials investigating 93 compounds/combinations, only 25 (26.9.0%) had any PubMed-available preclinical data in bleomycin.Since 2008, we observed a shift (from <5% to 37.4%) in the number of studies evaluating drugs in the therapeutic setting in the bleomycin model. While this shift is encouraging, more characterisation of early inflammation and appropriate preclinical therapeutic testing are still needed. This will facilitate fruitful drug development in IPF, and more therapeutic strategies for patient with this devastating disease.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Upagupta has nothing to disclose.Conflict of interest: Dr. Ask reports grants from Boehringer Ingelheim, grants from GSK, grants from Prometic, grants from Alkermes, grants from Pharmaxis, grants from Respivert, grants from Indalo, grants from Canadian Institutes for Health Research, grants from Kniksa, grants from Avalyn, grants from National Sciences and Engineering Research Council, grants from Ontario Thoracic Society, grants from Candadian Pulmonary Fibrosis Foundation, grants from Actelion, grants from Gilead, grants from Patara, grants from Synairgen, grants from Unity, outside the submitted work.Conflict of interest: Dr. Ayaub has nothing to disclose.Conflict of interest: Dr. Kolb reports grants and personal fees from Roche, grants and personal fees from Boehringer Ingelheim, grants from GSK, grants from Respivert, personal fees from Genoa, grants from Alkermes, grants from Pharmaxis, grants and personal fees from Prometic, personal fees from Indalo, personal fees from Third Pole, personal fees from Pieris, grants from Canadian Institute for Health Research, outside the submitted work.Conflict of interest: Dr. Bellaye has nothing to disclose.Conflict of interest: Dr. Chiko Shimbori has nothing to disclose.Conflict of interest: Mr. Philipp Kolb has nothing to disclose.Conflict of interest: Dr. Gauldie has nothing to disclose.Conflict of interest: Miss Megan Vierhout has nothing to disclose.Conflict of interest: Dr. Inman has nothing to disclose.