Dataset Information

Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies.

ABSTRACT: Idiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma - i.e. reduced compliance. Passive respiratory mechanics were measured. ^81mKr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with ^99mTc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. ^81mKr gas-ventilation and ^99mTc-DTPA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials.

SUBMITTER: Montigaud Y

PROVIDER: S-EPMC6884587 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies.

Montigaud Yoann Y Périnel-Ragey Sophie S Plantier Laurent L Leclerc Lara L Goy Clémence C Clotagatide Anthony A Prévôt Nathalie N Pourchez Jérémie J

Scientific reports 20191129 1

Idiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Thr ...[more]

PMID: 31784683

Similar Datasets

Project description:BackgroundThere is no standard definition of respiratory-related hospitalisation, a common end-point in idiopathic pulmonary fibrosis (IPF) clinical trials. As diverse aetiologies and complicating comorbidities can present similarly, external adjudication is sometimes employed to achieve standardisation of these events.MethodsAn algorithm for respiratory-related hospitalisation was developed through a literature review of IPF clinical trials with respiratory-related hospitalisation as an end-point. Experts reviewed the algorithm until a consensus was reached. The algorithm was validated using data from the phase 3 ISABELA trials (clinicaltrials.gov identifiers NCT03711162 and NCT03733444), by assessing concordance between nonadjudicated, investigator-defined, respiratory-related hospitalisations and those defined by the adjudication committee using the algorithm.ResultsThe algorithm classifies respiratory-related hospitalisation according to cause: extraparenchymal (worsening respiratory symptoms due to left heart failure, volume overload, pulmonary embolism, pneumothorax or trauma); other (respiratory tract infection, right heart failure or exacerbation of COPD); "definite" acute exacerbation of IPF (AEIPF) (worsening respiratory symptoms within 1 month, with radiological or histological evidence of diffuse alveolar damage); or "suspected" AEIPF (as for "definite" AEIPF, but with no radiological or histological evidence of diffuse alveolar damage). Exacerbations ("definite" or "suspected") with identified triggers (infective, post-procedural or traumatic, drug toxicity- or aspiration-related) are classed as "known AEIPF"; "idiopathic AEIPF" refers to exacerbations with no identified trigger. In the ISABELA programme, there was 94% concordance between investigator- and adjudication committee-determined causes of respiratory-related hospitalisation.ConclusionThe algorithm could help to ensure consistency in the reporting of respiratory-related hospitalisation in IPF trials, optimising its utility as an end-point.

Dataset Information

Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies.

Publications

Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets