THE PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY-DISEASE OF HORSES

Present evidence suggests that chronic obstructive pulmonary disease ( COPD) of horses is a delayed hypersensitivity response to inhaled anti gens, 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 ac companied by increased levels of histamine in bronchoalveolar lavage f luid, increased plasma levels of the inflammatory mediators thromboxan e and 15-hydroxyeicosatetraenoic acid (15-HETE), and a decrease in the production of prostaglandin (PG) E(2) by the airway mucosa. During ac ute exacerbations of COPD, airways exhibit nonspecific hyperresponsive ness and become obstructed as a result of bronchospasm and the accumul ation 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 incre ase 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 ne rvous system and the production of PGE(2) in affected horses. The diff use airway obstruction leads to uneven distribution of ventilation, ve ntilation/perfusion mismatching, and hypoxaemia. As a result of the in creased respiratory drive caused by hypoxaemia and the presence of air way obstruction, horses adopt a characteristic breathing strategy in w hich very high peak flows at the start of exhalation rapidly diminish as exhalation proceeds.