pulmonary fibrosis

Respiratory disorders of the donkey

Donkeys suffer from the same respiratory diseases as horses; however, owing to their nonathletic nature many conditions can present in a more advanced state before becoming clinically apparent. Anatomically, their respiratory tract is similar to the horse, with certain species-specific differences that are important to be aware of. Often donkeys do not receive the same level of routine care as horses, so many are not vaccinated against respiratory pathogens such as influenza or herpesviruses. Donkeys can act as a reservoir for certain infectious and parasitic respiratory diseases and the interpretation of diagnostic tests needs to be carried out with caution.

Volume
35
Issue
3
Start page
561
End page
573
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Respiratory disease in the donkey

The donkey suffers from a similar range of respiratory diseases as the horse; however, there are a number of subtle variations, knowledge of which can influence the success of treatment. As an animal adapted to a semi-arid terrain, there are variations in physiology, anatomy and disease susceptibility. The nonathletic nature of the donkey means that delayed presentation is common with many diseases and, while there may be enhanced resistance to some transboundary and parasitic diseases, there may be equal or increased severity of illness to some endemic diseases, e.g. equine influenza. Donkeys frequently live to geriatric ages and the clinician should be aware of the increased risk of conditions such as tracheal collapse, fibrosing pneumonia and neoplasia in this age group. As with any condition that causes stress and inappetance, respiratory disease in the donkey may be complicated by hyperlipaemia and good nursing care is an essential component of treatment.

Volume
24
Issue
9
Start page
469
End page
478
Publication date

Chronic pleuropulmonary fibrosis and elastosis of aged donkeys - similarities to human pleuroparenchymal fibroelastosis (PPFE)

Donkey Pulmonary Fibrosis (DPF) is a spontaneous syndrome of aged donkeys with high prevalence (35%). No previous detailed characterisation of DPF has been performed. We sought to determine the similarities of DPF to recognised patterns of human pulmonary fibrosis.

Whole lungs were collected from 32 aged donkeys at routine necropsy. Gross examination revealed pulmonary fibrosis in 19 donkeys (DPF cases), while 13 (controls) had grossly normal lungs. Eighteen whole inflated ex vivo lungs (11 DPF, 7 controls) were imaged with high resolution computed tomography (HRCT), while the remainder were sectioned and photographed. Tissue samples were collected from all lungs for histopathological evaluation using a standardised protocol. HRCT images and histology sections were reviewed independently and blindly. Lung tissue was analysed for herpes virus, fungal hyphae, mycobacteria and dust content.

Ten of 19 DPF lungs were categorised as being 'consistent with' pleuroparenchymal fibroelastosis (PPFE) according to previously defined histological and imaging criteria. All 10 PPFE-like lungs had marked pleural and subpleural fibrosis, predominantly within the upper lung zone, with accompanying intra-alveolar fibrosis and elastosis. Asinine herpesvirus (AsHV) was ubiquitously expressed within control and DPF lung tissue. No other aetiological agents were identified.

Many cases of DPF share key pathological and imaging features with human PPFE, a rare interstitial pneumonia. Consequently, further study of DPF may help elucidate the aetiopathogenesis of human PPFE.

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Characterisation of asinine pulmonary fibrosis and similarities to an emerging human interstitial lung disease

Amy Miele
Kevin Dhaliwal
Nicole du Toit
Harriet Brooks
Sionagh H. Smith
W. Wallace
J. Murchison
T. Schwarz
N. Hirani
C. Haslett
Bruce McGorum
Presentation date

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

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

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Investigation of asinine pulmonary fibrosis

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Methodology

Non-invasive clinical examination, case/control examination of post mortem material, case review of clinical and pathology records. Whole lungs were collected from 32 aged donkeys (19 APF-like on gross examination and 13 controls) at routine necropsy from 2 UK Donkey Sanctuaries between June 2009 and January 2013. 18 whole inflated ex vivo lungs (11 APF, 7 controls) were imaged with high resolution computed tomography (HRCT) while the remainder were sectioned and photographed digitally. Tissue samples were collected from all lungsinto 10% buffered formalin and processed into paraffin blocks for histopathological evaluation . HRCT images and histology sections were objectively reviewed and categorised as, 'consistent with' or 'inconsistent with' characteristics of pleuroparenchymal fibroelastosis (PPFE). Tissue samples from 8 lungs were also processed for DNA extraction and PCR. Lung sections with granulomatomous inflammation were analysed for fungal hyphae, and Mycobacteria. X-ray diffraction was used to identify both fibrous and non-fibrous dust content.

Aims
  1. To characterise Asinine Pulmonary Fibrosis (APF) on a gross, histopathological and molecular level.
  2. To perform an epidemiological study, encompassing case histories, environmental management, and potential pathogen and dust exposure.
  3. Evaluating non-invasive clinical techniques including detailed clinical examination, pulse oximetry and thoracic ultrasound as early diagnostic and disease monitoring tools.
Objectives

To examine ex vivo lung tissue from a small cohort of aged donkeys with a high prevalence (35%) of fibrosing interstitial lung disease named Asinine Pulmonary Fibrosis.

Results

There was no statistically significant difference between the age of APF and control donkeys. Ten of 19 APF cases were categorised as being consistent with PPFE according to the defined histological and imaging criteria sharing key features with human PPFE. As donkeys are quadruped, the dorsal lung equates to the human upper zone. All 10 PPFE-like lungs had grossly visible visceral pleural fibrosis on the dorsal/costal surface, with no involvement of the parietal pleura. Histologically, all 10 PPFE-like lungs had marked pleural and subpleural fibrosis, predominantly within the upper lung zone, with accompanying intra-alveolar fibrosis and elastosis. It is possible that some of the DPF lungs classified as 'inconsistent' with PPFE may represent an earlier stage of PPFE-like disease. All control cases were classified as inconsistent with PPFE on histology and HRCT. Asinine herpes virus was ubiquitously expressed within both control and APF lung tissue. No other etiologic agents were identified. X-ray diffraction analysis revealed dust contents and small numbers of fibrous and non-fibrous particles.

Conclusions

This study showed that over 50% of donkeys with DPF shared key pathological and imaging characteristics of human PPFE, a rare and usually idiopathic interstitial pneumonia. Further study of APF may yield valuable information to help elucidate the etiopathogenesis of this emerging human disease; in particular how recurrent lower respiratory tract infections may contribute to the pathogenesis of PPFE.

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