June 16, 2016

Rare Cause of Pulmonary Hypertension in Humans Has Been Identified in Dogs

The first report of pulmonary veno-occlusive disease (PVOD) in dogs has been published.
By Laurie Anne Walden, DVM, ELS
The first report of pulmonary veno-occlusive disease (PVOD) in dogs has been published in Veterinary Pathology. PVOD is a rare cause of pulmonary hypertension in humans, with an estimated incidence of 0.1 to 0.2 cases per million people.
 
In humans, PVOD is a form of pulmonary arterial hypertension that causes clinically severe disease. It is characterized by occlusion of small pulmonary veins and venules, resulting in upstream congestion of alveolar capillaries. Lesions within the pulmonary artery are also common. The cause in humans is not entirely clear, but toxins, viral infection, genetics, and immune-mediated causes have been proposed. The only treatment is lung transplantation. Without transplantation, the average survival time is 2 years after diagnosis.
 
The study authors identified lesions similar to those of human PVOD in lung samples from 11 dogs that died of respiratory disease. The dogs were of various breeds and geographic locations (Michigan, Massachusetts, California, and the United Kingdom). The most common presenting signs were acute respiratory distress, cough, and inappetence. Five of the dogs were euthanized soon after presentation (within hours, according to the authors) because of the rapid progression of their disease. The longest survival time before euthanasia was 6 months.
 
On gross pathology, the dogs’ lungs were edematous and consolidated, with many foci of congestion. Histopathologic examination revealed occlusive remodeling of small pulmonary veins, alveolar capillary congestion, foci of pulmonary capillary hemangiomatosis, and increased numbers of alveolar hemosiderophages—findings that are all typical of PVOD in humans. Six of the dogs also had pulmonary arterial remodeling. Transmission electron microscopy and immunohistochemical labeling showed that the occlusion in the pulmonary veins was partially composed of smooth muscle cells.
 
The dogs in this study were all adults (average age, 10.5 years). In contrast, PVOD in humans is more prevalent in children and young adults, although it also occurs in older adults. The clinical progression in the dogs was rapid; in most human patients the disease is reported to progress more slowly. The authors suggest that the incidence of PVOD could be higher in dogs than in people, speculating that many canine cases have gone undiagnosed. The cause of PVOD in dogs is unknown.
 
A mouse model for investigating PVOD in the laboratory has been developed. The authors write that canine PVOD could be a spontaneous model for research into the pathogenesis of the disease. “PVOD is a poorly understood disease not just because it’s so rare, but also because there’ve been no other animals known to have the disease,” said lead author Kurt Williams, of the College of Veterinary Medicine at Michigan State University, in an interview in MSUToday. “Our finding changes things.”
 
Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University in 1994. After an internship at Auburn University College of Veterinary Medicine, she returned to North Carolina, where she has been in companion animal general practice for over 20 years. Dr. Walden is also a board-certified Editor in the Life Sciences and owner of Walden Medical Writing 

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