The pathogenesis of chronic obstructive pulmonary disease of horses.
Abstract: Present evidence suggests that chronic obstructive pulmonary disease (COPD) of horses is a delayed hypersensitivity response to inhaled antigens, particularly the thermophilic moulds and actinomycetes that grow in damp hay. Within several hours of exposing COPD-susceptible horses to such hay, neutrophils invade the lung and accumulate in the lumens of airways, particularly bronchioles. The inflammatory response is accompanied by increased levels of histamine in bronchoalveolar lavage fluid, increased plasma levels of the inflammatory mediators thromboxane and 15-hydroxyeicosatetraenoic acid (15-HETE), and a decrease in the production of prostaglandin (PG) E2 by the airway mucosa. During acute exacerbations of COPD, airways exhibit nonspecific hyperresponsiveness and become obstructed as a result of bronchospasm and the accumulation of mucus and exudates. Bronchospasm is due largely to activation of smooth muscle muscarinic receptors by acetylcholine (ACh). Because the in vitro response of smooth muscle to ACh is unaltered, the increase in airway smooth muscle tone is probably a result of activation of airway reflexes by inflammatory mediators and decreases in inhibitory mechanisms such as the intrapulmonary nonadrenergic noncholinergic nervous system and the production of PGE2 in affected horses. The diffuse airway obstruction leads to uneven distribution of ventilation, ventilation/perfusion mismatching, and hypoxaemia. As a result of the increased respiratory drive caused by hypoxaemia and the presence of airway obstruction, horses adopt a characteristic breathing strategy in which very high peak flows at the start of exhalation rapidly diminish as exhalation proceeds.
Publication Date: 1995-05-01 PubMed ID: 8762605DOI: 10.1016/s0007-1935(96)80101-1Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
- Review
Summary
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This study focuses on understanding the cause and mechanism of chronic obstructive pulmonary disease (COPD) in horses, suggesting it lies in an immune response to inhaled antigens from certain moulds and actinomycetes in damp hay, leading to inflammation, an imbalance in certain chemical levels, and breathing difficulties.
Pathogenesis of COPD in Horses
- The research paper begins by asserting that chronic obstructive pulmonary disease (COPD) in horses appears to be a delayed hypersensitivity response to inhaled antigens. Particularly, these antigens originate from thermophilic moulds and actinomycetes that grow in damp hay. Essentially, the horse’s immune system reacts excessively and slowly to the typically harmless substances, leading to inflammation in the lungs.
- When horses that are susceptible to COPD are exposed to damp hay, neutrophils, a type of white blood cell, invade the lungs within a few hours. They primarily accumulate in the airways—specifically, the bronchioles —where they trigger an inflammatory response.
Indicators and Consequences of Inflammation
- The inflammation is characterized by several changes in the levels of substances in the bronchoalveolar lavage fluid and plasma. This includes an increase in levels of histamine, thromboxane, and 15-hydroxyeicosatetraenoic acid (15-HETE), and a decrease in the production of prostaglandin (PG) E2 by the airway mucosa. Each of these mediators play various roles in the inflammation process and, in this context, contribute to the dysfunction of the airway.
- The paper goes on to discuss the treatment of acute exacerbations of COPD which result in the airways being obstructed. This obstruction is due to bronchospasm (sudden constriction of the muscles in the walls of the bronchioles) combined with an accumulation of mucus and exudates (fluid emitted by an open wound).
Role of Acetylcholine and Loss of Inhibitory Mechanisms
- Bronchospasms are attributed to the activation of muscarinic receptors in the smooth muscles of the airway by acetylcholine (ACh), a neurotransmitter. However, the paper notes that the response of smooth muscle to ACh is the same in healthy tissue, suggesting that the hyperactivity in COPD-affected horses is due to an increase in airway reflexes triggered by inflammatory mediators.
- Furthermore, it mentions a decrease in certain mechanisms that would typically limit bronchospasms, such as the intrapulmonary nonadrenergic noncholinergic nervous system and the production of PGE2. Combined, these changes culminate in an uneven distribution of ventilation, ventilation/perfusion mismatching, and hypoxaemia (a decrease in the level of oxygen in the blood).
Respiratory Changes and Adaptation
- As a direct result of the obstructed airways and hypoxaemia, horses with COPD increase their respiratory drive. They develop a characteristic breathing strategy where extraordinarily high peak flows at the start of exhalation diminish as exhalation continues. This pattern is an adaptive response aiming to optimize breathing in the face of significant ventilation obstacles.
Cite This Article
APA
Robinson NE, Derksen FJ, Olszewski MA, Buechner-Maxwell VA.
(1995).
The pathogenesis of chronic obstructive pulmonary disease of horses.
Br Vet J, 152(3), 283-306.
https://doi.org/10.1016/s0007-1935(96)80101-1 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA.
MeSH Terms
- Animals
- Bronchial Spasm / complications
- Bronchial Spasm / veterinary
- Forecasting
- Horse Diseases / etiology
- Horse Diseases / pathology
- Horses
- Inflammation / complications
- Inflammation / veterinary
- Lung Diseases, Obstructive / etiology
- Lung Diseases, Obstructive / pathology
- Lung Diseases, Obstructive / veterinary
- Research
Grant Funding
- HL 49494 / NHLBI NIH HHS
Citations
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