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by I Mahmutovic Persson, H Falk Håkansson, J Persson, P Önnervik, L E. Olsson, K Von Wachenfeldt  on behalf of the TRISTAN Consortium

ERJ Open Research 2020; 6(suppl 5): 66. doi: 10.1183/23120541.LSC-2020.66

Abstract

Drug-induced interstitial lung disease (DIILD) is highly underdiagnosed and very few preclinical models exist to study these event. To address the increasing issue of drug-induced toxicity, we aimed to develop two translational models in rats using two different drugs; Bleomycin (BL) or Nitrofurantoin (NF). Here long-term systemic exposure to medication was applied to mimic clinical features.

Methods:
Sprague-Dawley rats received BL or NF challenge subcutaneously, 3 days/week during 1-4 weeks. MRI was performed at week 5. At termination (week 1, 2, 3, 4 and 5), BAL was collected and analysed for total protein and inflammatory cells. Lungs were further analysed by histology.

Results:
The two models showed diverse pathological alteration in the lungs (Figure). BL rats presented weight loss and significant increase (p<0.001) in BALF neutrophils. Low progression of fibrosis and hypertrophy of endothelium was seen in the BL group over time. NF group showed signs of lipid pneumonia and fibrotic loci formation early on, which stayed throughout the 4-5 weeks’ observation. NF rats gained weight and had elevated macrophage count in their BALF, vs control. Lesions were observed by MRI.

Conclusion:
Here we present two DIILD models in rat, with distinct pathological changes over time showing two examples of alterations in the lung upon medication. These models serve as platforms for further biomarker development in DIILD.