Cellular Basis of Chronic Obstructive Pulmonary Disease in Horses

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Chronic obstructive pulmonary disease (COPD) is an inflammatory obstructive disease of the airways characterized with hypersensitivity of the airway tissues to various allergens, most commonly the fungi contained in the poor‐quality hay and straw bedding—Saccharopolyspora rectivirgula, Aspergillus fumigatus, and Thermoactinomyces vulgaris. It is manifested clinically in middle‐aged horses with recurrent episodes of dyspnea, chronic cough, and their reduced athletic and working capacity. Pulmonary emphysema and lack of pulmonary collapse are the most common gross lesion. Pathohistological findings in horses with COPD are chronic bronchitis/bronchiolitis, with characteristic changes in lumen, mucosa, submucosa, and smooth muscle layer and alveolar emphysema, both distensive and destructive form. Increased immunoreactivity in lungs and tracheobronchial lymph nodes is also noted. Most common lesions seen on cytology imprint smears from tracheal bifurcation is thick, viscous, PAS‐positive mucus that forms Curschmann's spirals. Dominant cell population consists of desquamated airway epithelial cells, as well as eosinophils, neutrophils, mast cells, erythrocytes, and alveolar macrophages. Primary pulmonary pathogens as well as potential contaminants and secondary infection agents were isolated bacteriologically from lung samples. All of the aforementioned findings correlate pointing to the fact that chronic bronchitis/bronchiolitis represents a basic substrate of COPD, which have combined inflammatory and immunological etiology, and emphysema is secondary to airway obstruction.

Introduction

Because respiratory diseases are widely spread among the horse population and account for a substantial share of pathology of the animal species, study of chronic obstructive pulmonary disease (COPD) in horses is of great importance. COPD belongs to the group of chronic respiratory diseases that reduce the value of the sports animals and working capacity of the draught animals. The importance of the study is further illustrated by the fact that COPD is markedly similar to allergic, atopic, extrinsic asthma in humans. Study of pathogenesis and therapy of the COPD in horses may contribute to the body of knowledge in pulmonology and promote treatment of asthma and chronic inflammatory disease of airways occurring in humans hypersensitive to various known and unknowns environmental stimuli. COPD is an inflammatory obstructive disease of the airways characterized with hypersensitivity of the airway tissues to various allergens, most commonly the fungi contained in poor‐quality hay and straw bedding (S. rectivirgula, A. fumigatus, and T. vulgaris). It is manifested clinically in middle‐aged horses with recurrent episodes of dyspnea, chronic cough, and their reduced athletic and working capacity.

The disease is commonly called pursy or chronic alveolar emphysema, but there are many synonyms, because all authors studying this issue proposed a name for the disease: heaves, broken wind, RAO (Recurrent Airway Obstruction), chronic bronchiolitis‐emphysema complex, chronic small airway disease, alveolar emphysema, chronic bronchiolitis, allergic bronchiolitis, asthma, asthmatic bronchiolitis, chronic cough, chronic pulmonary emphysema, chronic bronchitis/bronchiolitis, chronic pulmonary disease, hypersensitive pneumopathy, hyperreactive airway disease, chronic airway reactivity, and hay sickness (Rooney and Robertson, 1996).

This disease is encountered in horses that spend a lot of time in poorly aired dusty stables during winter, although there is a special type of the disease that also occurs in the summer. The reference literature states that the age at which the disease occurs for the first time varies from 4 to 8 years or more. It is most frequently encountered in sports horses in the following disciplines: show jumping, equestrian dressage, endurance (endurance race, cross‐country riding with regular veterinary check‐ups in which the horse pulse must not exceed 64 beats per minute), eventing (comprises show jumping, dressage, and cross‐country with show jumping), but it also occurs in horses that are used for recreational riding, in riding schools, etc. (Art et al., 1998).

The disease presents itself in two forms: (1) typical form of COPD in the winter months in horses that spend longer time in unaired, dusty stables and are hay‐fed; and (2) Summer pasture‐associated obstructive pulmonary disease (SPAOPD)— this form of the disease is encountered in the southeast part of the United States, California, and the United Kingdom during the summer when the horses are grazing and when the weather is warm and humid (Costa 2001, Robinson 2001, Seahorn 1993). Both in humans and horses the genetic base of COPD is considered to be very important. In the pathogenesis of equestrian COPD, an important role is played by T lymphocytes, CD4+ Th1 that release: IL‐8, MIP‐2, LTB‐4, and ICAM‐1, whereas CD4+ Th2 lymphocytes produce IL‐4, IL‐13, and IL‐5.

Pathogenesis of the disease has not been fully elucidated, but some hypotheses have been proposed suggesting the development of the disease. With genetic predisposition, noxae (recurrent and uncured viral and bacterial infections of the airways, noxious effect of protease, and endotoxins) lead to lesions on the airway epithelium—loss of the cilia from the ciliary epithelium, desquamation of the epithelial cells of bronchioli and bronchi, as well as denudation of the basal membrane. Denudation of the basal membrane enables the antigen to establish a direct contact with the immunologically active tissues and as a result respiratory tissues become hypersensitive (McPherson 1974, Moore 2004, Trailovic 2000).

The main role of CD4+ Th1 that produce IL‐4, IL‐5 and IL‐13 activated mastocytes, platelets, epithelial cells, and substances originating from these cells—histamine, bradykinin, LTC‐4, LTD‐4, PAF, PGD2, PGF2α—has been recognized in the pathogenesis of asthma. These substances lead to a series of pathological changes characteristic of both diseases. Macroscopically, appearance of the lung is mainly unchanged, but some authors suggest that in horses suffering from COPD the lungs usually do not collapse at exenteration from the chest or appear voluminous and excessively inflated, pale pink, and occasionally with imprints of the ribs seen. Sometimes there is emphysema as well as thick mucus that may be squeezed out of the lung section when pressed.

The pathohistological findings are very characteristic. The main pathohistological substrates of COPD include bronchitis and bronchiolitis that are characterized with changes on the mucosal and muscular layers of bronchi and bronchioli, in the peribronchial and peribronchiolar tissues as well as accumulation of content in the airways, their obstruction, and consequent development of secondary emphysema and atelectasis. Regardless of the fact that the disease was recognized long ago, few data exist on the pathogenesis, which makes the diagnosis establishing difficult. In addition to standard diagnostic methods, cytological smears obtained by bronchoalveolar and tracheobronchial lavage are also used. Moreover, imprints from the mucosal tissue in the tracheal bifurcation make postmortem diagnostic substantially easier and substantiates the diagnosis of the disease.

Section snippets

Lungs

Histology of the lungs is composed of conducting elements (lung conducting ways) composed of the bronchi and bronchioli; transitory elements composed of respiratory bronchioli; respiratory elements comprising alveolar channels, alveolar sacs, and alveoli; and stromal elements of the lungs represented by vascular and lymph vessels and nerves. The conducting elements start where the trachea branches into the right and main left bronchus that are initially extrapulmonary situated where in the lung

Cytological Features of Equine Lungs

The pulmonary parenchyma contain the subepithelial and free mastocytes that have, on the surface, incorporated E class immunoglobulins (IgE) and as a response to stimulation by specific antigen release histamine, heparin, arachidonic acid metabolites, platelet activation factor, and hemotoxic factors. Consequently, they play an important role in pathogenesis of some major equine diseases such as COPD and infection by pulmonary nematodes (Ainsworth and Biller, 1998).

Secretion of the lower

Chronic Obstructive Pulmonary Disease (COPD) in Horses

In the respiratory system pathology COPD plays a very important role. COPD is an inflammatory obstructive disease of the airways that becomes clinically manifested in middle aged horses as recurrent episodes of dyspnea, chronic cough, and impaired sports and working capacity of horses (Robinson, 2001).

Conclusions and Perspectives

Cytological analysis of mucosal imprints of the tracheal bifurcation suggests the presence of an asthmatic pattern analogous to that of humans (a large number of eosinophils, mucosal spirals, Creola bodies) but histological examinations of pulmonary parenchyma and bronchi do not correspond to human asthma, because hyalinization of the basal membrane is missing (Dunnill 1960, Salvato 1968, Sanerkin 1965). Obviously, allergic component plays a very important role in the pathogenesis of COPD. The

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