asinine

Characterisation of Asinine Pulmonary Fibrosis and similarities to an emerging human interstitial lung disease

Citation

Amy Miele, Nicole du Toit, Harriet Brooks, Sionagh H. Smith, W Wallace, C Dhaliwal, J Murchison, T Schwarz, N Hirani, C Haslett, K Dhaliwal, Bruce McGorum. Characterisation of Asinine Pulmonary Fibrosis and similarities to an emerging human interstitial lung disease. Presented at BSAS Annual Meeting 2013. (16 April - 17 April 2013). Nottingham, UK.

Authors
Presentation details
Date presented: 
Tuesday 16 April 2013
Event name: 
BSAS Annual Meeting 2013
Abstract

Introduction

Pleuroparenchymal Fibroelastosis (PPFE) is an emerging, idiopathic and likely under diagnosed condition that does not fall within any of the current classifications of human interstitial lung diseases (Frankel et al, 2004). Key features include an upper zone predominance of pleural fibrosis with associated intra-alveolar fibrosis and elastosis of alveolar walls (Frankel et al, 2004; Reddy et al., 2012). The objective of our study was to examine ex vivo lung tissue from a small cohort of aged donkeys with a high prevalence (35%) of fibrosing interstitial lung disease termed Asinine Pulmonary Fibrosis (APF;Morrow et al, 2010). APF is a potentially debilitating and untreatable syndrome of donkeys that is poorly understood and rarely documented. We hypothesise that some cases of APF share several key gross and histopathological features of PPFE and propose that both can be linked to recurrent respiratory infection.

Materials and Methods

Whole asinine lungs were collected from 30 aged donkeys at routine necropsy examination at two UK donkey sanctuaries between June 2009 and September 2012. 19 ‘APF affected’ donkeys had evidence of pulmonary fibrosis on gross examination while 11 ‘control’ animals had grossly normal lungs. Lungs were manually inflated prior to clamping of the trachea and gross images were photographed with a digital camera. 16 whole inflated ex vivo lungs (11 APF, 5 controls) were then imaged with high resolution computed tomography (HRCT). Tissue samples were collected from each lung into 10% buffered formalin according to a standard protocol before undergoing routine processing to paraffin blocks. Sections were routinely stained with haematoxylin and eosin (H&E), elastic van Gieson (EVG) and Masson’s trichrome (MT). HRCT images and histology sections were reviewed independently and blindly by a radiologist and pathologist respectively from both medical and veterinary fields. Sections and HRCT images were categorised as ‘definite’, ‘consistent with’ or ‘inconsistent with’ with regard to PPFE using criteria described by Reddy et al (2012). Cases were categorised as ‘definite’ on either CT or histology if there was pleural thickening with associated subpleural fibrosis either concentrated in upper or dorsal lung lobes (with respect to CT evaluation) or demonstrating intra-alveolar fibrosis with alveolar septal elastosis (with respect to histological evaluation of EVG sections). CT images were categorised as ‘consistent with’ if there was dorsal lobe pleural thickening and associated subpleural fibrosis but the distribution of fibrosis was not concentrated in the dorsal lung lobes or there was evidence of coexistent lung disease elsewhere. Histology sections were categorised as ‘consistent with’ if intra-alveolar fibrosis was present but either not associated with pleural fibrosis, not predominantly subpleural or not in a dorsal lobe biopsy. ‘Inconsistent with’ was assigned to cases that lacked the aforementioned features either on CT or histology.

Results

Ages of ‘APF affected’ (median 31 years, range 14-53) and ‘control’ (median 28 years, range 4-36) donkeys at the time of death were not significantly different (Mann Whitney, p>0.05). The donkeys comprised 11 geldings and 19 entire jennies. 10/19 APF affected cases were euthanased on humane grounds due to respiratory disease, while 9 were euthanased on humane grounds for other reasons and pulmonary fibrosis was an incidental post mortem finding.
10/19 APF affected cases were categorised as either ‘definite’ or ‘consistent with’ PPFE on histological evaluation, while 9 showed histological evidence of pleuroparenchymal fibrosis but this did not have an intra-alveolar distribution. 8/11 APF affected cases were categorised as either ‘definite’ or ‘consistent with’ PPFE on evaluation of HRCT images. Two of the remaining 3 cases showed pleural and subpleural fibrosis concentrated in the ventral lung lobes while one demonstrated diffuse ground glass opacity with minimal pleural fibrosis. Histological evaluation of these three cases also resulted in an ‘inconsistent with’ classification. All control cases were classified as ‘inconsistent with’ on both HRCT and histology.

Conclusions

APF is a common yet rarely diagnosed and apparently untreatable syndrome of aged donkeys. This study is the first to combine HRCT and histological data to characterise and document pathological features of APF. We conclude that the majority of cases of APF share key pathological features with human PPFE. Further study of APF may yield valuable information to help elucidate the aetiopathogenesis of this emerging human disease.

Acknowledgements The authors gratefully acknowledge funding from the MRC.

References
Frankel, S.K., Cool, C.D., Lynch, D.A., & Brown, K.K., 2004, CHEST Journal 126(6): 2007.
Morrow, L., Smith, K., Piercy, R., et al., 2010, Journal of Comparative Pathology.
Reddy, T.L., Tominaga, M., Hansell, D.M., et al., 2012, European Respiratory Journal 40(2): 377.

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