Systematic review: In vivo imaging in animal models relevant to drug-induced Interstitial lung disease (DIILD)

Translational Imaging Biomarkers (IB) are needed to avoid or manage drug-toxicity, resulting in drug-induced interstitial lung disease (DIILD). We reviewed the literature on in vivo imaging to detect and assess lung lesions in animal models with relevance to DIILD and with pathological changes resembling clinical DIILD. Methods: A systematical search was carried out using the 3 databases PubMed, EMBASE and Scopus, searching for “Animal models”, “Imaging”, “Lung disease” and “Drugs”. Eligibility criteria for inclusion were limited to original articles in English, published or in press from 1970 to 13th May 2017. From a total of 4354 articles, three reviewers selected papers for inclusion, while additional 6 reviewers (total 9) extracted data from 218 articles selected. Consensus was achieved by discussion. Results: 130 out of 218 papers were found eligible for data extraction. Single or multiple inducing agents to produce lung injury were described, in eight different animal species. Exposure, duration and dosing of substances varied from extremely non-physiological to clinically relevant levels. In total, nine different imaging modalities were used, and more than half of the studies were longitudinal. 24 studies used more than one imaging modality. The majority of studies also reported other biomarkers and- or histological confirmation of the imaging results. Inflammation and fibrosis pathologies resembling DIILD were described in 38 papers, but only two explicitly addressed drug-induced toxicity. Conclusions: There is a need for better animal IB models to help interpret DIILD IB findings on incidence, progression and reversibility in patients.