Preliminary observations on inhalation and intradermal challenges of horses with oil seed rape.

Horses with asymptomatic or symptomatic chronic obstructive pulmonary disease (COPD) and control horses were challenged with oil seed rape either by exposure to a field of flowering Brassica campestris for six days, or by an inhalation challenge with freshly collected pollen from Brassica napus, or by inhalation challenge with a commercial extract of B napus pollen. Clinical and bronchoscopic examinations showed that the challenges did not induce detectable pulmonary disease in the control or asymptomatic COPD affected horses and did not significantly affect their pulmonary mechanics, arterial blood gas tensions, arterial pH or the cytology of bronchoalveolar lavage fluid. However, the challenges with fresh B napus pollen and the commercial extract of B napus pollen exacerbated the pulmonary disease in some of the symptomatic horses, possibly owing to non-specific toxicity or non-specific bronchial hyperresponsiveness. Intradermal testing with the commercial extract of B napus pollen suggested that none of the horses were hypersensitive to this agent.     

Chronic obstructive pulmonary disease in the horse. 2: Therapy

The therapy of equine chronic obstructive pulmonary disease (COPD) essentially entails minimising the horse's exposure to the aetiological antigens which are predominantly thermophilic actinomycetes and moulds occurring in hay and straw. This can be achieved, for example, by keeping affected horses permanently out of doors, or when stabled, using shredded paper, wood shavings or peat moss as bedding and feeding a complete cubed diet. There should be no supplementary hay feeding apart from dust-free vacuum-packed hay. Applying such measures generally allows horses to become asymptomatic in seven to 14 days. Bronchodilators and corticosteroids bring about a marked, but temporary, improvement and can be of value in the treatment of acute attacks. The use of oral bronchodilators in combination with environmental control measures may hasten the remission of clinical signs in affected horse. Inhaled sodium cromoglycate can be used prophylactically in asymptomatic horses to prevent the onset of COPD when unavoidable antigen exposure is anticipated.     

Chronic obstructive pulmonary disease (COPD): factors influencing the occurrence.

Breed, age, weight, type of work performed, seasonal onset, poor ventilation and exposure to moulds in the habitat were investigated in relation to the occurrence of chronic obstructive pulmonary disease (COPD). COPD was most commonly detected in showjumping and hacking horses. The older a horse, the more likely it was to become affected although most were 6 to 10 years of age. Of the horses in this sample of the population, which was not a random one, thoroughbred horses were affected least and ponies most often. The high incidence in ponies was related to their more frequent exposure to poor quality fodder and bedding. Most horses are exposed to the hazard of moulds, but more affected horses were so exposed than those not affected with COPD. Poor ventilation of the stable increased the chance of a horse becoming affected. Sex, body weight and season of onset of coughing had no influence on the occurrence of the disease.     

Pulmonary artery pressures in normal horses and in horses affected with chronic obstructive pulmonary disease

Horses clinically affected with chronic obstructive pulmonary disease (COPD) were found to have pulmonary artery hypertension which was associated with systemic arterial hypoxia. The pulmonary hypertension in symptomatic COPD-affected horses was partially reversible upon remission of clinical signs or by oxygen administration. The induction of acute hypoxaemia caused an increase in pulmonary artery pressure in both normal and COPD-affected horses.     

Interleukin-8 concentration and neutrophil chemotactic activity in bronchoalveolar lavage fluid of horses with chronic obstructive pulmonary disease following exposure to hay

OBJECTIVE: To analyze effects of hay dust exposure on interleukin-8 (IL-8) concentration, percentage of neutrophils, and neutrophil chemotactic activity in bronchoalveolar lavage fluid (BALF) of horses with chronic obstructive pulmonary disease (COPD). ANIMALS: 16 healthy horses and 29 horses with COPD. PROCEDURE: IL-8 concentration, percentage of neutrophils, and neutrophil chemotactic activity in BALF were measured. Values were analyzed with respect to hay dust exposure.These variables were also measured in 5 asymptomatic horses with COPD after the induction of clinical signs by changing feed from silage to hay. RESULTS: L-8 concentrations and chemotactic activity in BALF were greater in horses with COPD, compared with healthy horses, and greater in horses with COPD exposed to hay dust, compared with nonexposed affected horses. An increase in IL-8 concentration accompanied by an increase in percentage of neutrophils in BALF and development of clinical signs of COPD were induced in asymptomatic horses with COPD by changing feed from silage to hay. CONCLUSIONS AND CLINICAL RELEVANCE: Exposure of horses with COPD to hay dust components resulted in an increase in IL-8 secretion at the bronchoalveolar surface. This chemokine may play a role in the pathogenesis of COPD, because it causes neutrophil accumulation in the bronchoalveolar space. Our results underscore the importance of eliminating dust sources for the treatment and prevention of COPD in horses.     

Clinical signs, evaluation of bronchoalveolar lavage fluid, and assessment of pulmonary function in horses with inflammatory respiratory disease

OBJECTIVE: To evaluate the association among clinical signs, results of cytologic evaluation of bronchoalveolar lavage (BAL) fluid, and measures of pulmonary function in horses with inflammatory respiratory disease. ANIMALS: 9 healthy horses, 5 horses with inflammatory airway disease (IAD), and 9 horses with chronic obstructive pulmonary disease (COPD). PROCEDURES: Clinical examination, lung function tests, and BAL were performed on each horse. RESULTS: Standard lung mechanics of horses with exacerbated COPD differed significantly from those of healthy horses; however, there were few differences among horses with IAD, horses with COPD during remission, and healthy horses. Most variables for forced expiration (FE) in horses with COPD or IAD differed significantly from those for healthy horses. Results of clinical examination had low to moderate sensitivity and predictive values for a diagnosis of COPD (range, 67 to 80%). Results of FE tests had high sensitivity, specificity, and predictive values for a diagnosis of COPD (79 to 100%), and results of standard lung mechanics tests had low sensitivity and predictive values (22 to 69%). Percentage of neutrophils in BAL fluid was highly sensitive (100%) but moderately specific (64%) for a diagnosis of COPD. CONCLUSIONS AND CLINICAL RELEVANCE: Clinical examination is moderately accurate for establishing a diagnosis of COPD. Forced expiration tests can specifically detect early signs of airway obstruction in horses with COPD and IAD that may otherwise be inapparent. Cytologic evaluation of BAL fluid allows early detection of inflammatory respiratory disease, but it is not specific for COPD.     

Effect of the 5-lipoxygenase inhibitor, fenleuton, on antigen-induced neutrophil accumulation and lung function changes in horses with chronic obstructive pulmonary disease

The leukotrienes (LT) LTD₄ and LTB₄ have been shown to cause bronchoconstriction and neutrophil accumulation, respectively, in horse lungs. Such changes are characteristic of the equine allergic respiratory disease, chronic obstructive pulmonary disease (COPD). To further investigate the role of these putative mediators in the pathogenesis of equine COPD the effect of a 5-lipoxygenase inhibitor, fenleuton, on antigen-induced changes in horses with this condition has been examined. Six horses with COPD underwent a series of four antigen challenges, one month apart, with placebo pre-treatment on three occasions and fenleuton (4 days oral dosing 5 mg/kg) pre-treatment on one occasion. Three horses received fenleuton prior to the second challenge and three horses received the drug prior to the fourth antigen challenge. Changes in radiolabelled neutrophil distribution, lung function and peripheral leucocyte counts were monitored on each occasion for 7 h following the start of antigen challenge. Antigen challenge caused an increase in radioactive counts over the lungs and a decrease in peripheral leucocyte count. Neither response was affected by fenleuton pre-treatment. Mean maximal changes in pleural pressure (ΔP_plmax) and respiratory rate were also unaffected by fenleuton pre-treatment. However, in the two horses which responded to antigen-challenge with a particularly marked increase in ΔP_plmax (>15 cm H₂O), prior administration of fenleuton reduced the response by 64 and 63%. These results suggest that 5-lipoxygenase inhibitors warrant further investigation as bronchodilators in equine COPD.     

Monthly, daily, and circadian variations of measurements of pulmonary mechanics in horses with chronic obstructive pulmonary disease

OBJECTIVES: To determine temporal variations of pulmonary function in horses without respiratory tract disease (controls) and horses with chronic obstructive pulmonary disease (COPD) and determine whether reversibility of airway obstruction after environmental control can be predicted by response to atropine administration. ANIMALS: 7 COPD-affected and 5 control horses. PROCEDURES: Pulmonary function testing was performed monthly during 3 consecutive months, daily for 5 consecutive days, and at 6-hour intervals for 24 hours before and after administration of atropine (0.02 mg/kg of body weight, i.v.) and after 5 consecutive months at pasture. Respiratory rate, tidal volume (VT), minute ventilation (VE), maximal change in transpulmonary pressure (deltaP(L)), pulmonary resistance (R(L)), and pulmonary elastance (E(L)) were calculated. RESULTS: COPD-affected horses had a significantly higher expiratory to inspiratory time ratio (T(E)/T(I)) and deltaP(L), E(L), and R(L) than horses without respiratory tract diseases during all periods and higher V(E) during monthly and daily evaluations. Daily variation in VT and monthly and circadian variation in E(L) were significant in COPD-affected horses. In control horses, significant changes were apparent only in T(E)/T(I) during daily recordings. In COPD-affected horses, reduction in deltaP(L), R(L), and E(L) was significant after atropine administration and after maintenance on pasture. CONCLUSIONS AND CLINICAL RELEVANCE: Despite variations in measurements of respiratory mechanics in both groups of horses, values remained significantly different between groups over time. Despite individual variation, measurements were repeatable during short and long periods. Response to administration of atropine to COPD-affected horses underestimated improvement in respiratory tract function that resulted from maintenance on pasture.     

Effect of hyonate administration on pulmonary function and indices of oxidative stress in COPD horses in clinical remission at rest and after exercise

Pulmonary function tests, bronchoalveolar lavages, and venous blood samplings were performed 24 hours before and one hour after a standardized strenous treadmill exercise test on six horses suffering from chronic obstructive pulmonary disease (COPD) in clinical remission. Pulmonary function test consisted of the measurement of the mechanics of breathing and arterial blood gases analyses. During the exercise tests, heart and respiratory rates, and venous plasma lactate, pH and packed cell volume were controlled. Venous blood was analyzed for some markers of the oxidative stress, i.e., hemolysate glutathione redox ratio and oxidized glutathione, and plasma uric acid. BAL was analyzed for cell cytology as well as for markers of oxidative stress, i.e., glutathione redox ratio, and isoprostanes concentration. The procedure was repeated twice, i.e., before and after two IV injections of 40mg hyaluronate administered at seven day intervals. The results were compared to assess a possible influence of the treatment on the pulmonary and systemic inflammatory and/or oxidative status of these horses.Hyaluronate did not influence the pulmonary function test or the physiological parameters recorded during exercise. There was a decrease in the percentage of BAL neutrophils after the treatment, suggesting a possible anti-inflammatory effect at the pulmonary level. As well, the concentration of isoprostanes in the pulmonary epithelium lining fluid was significantly lower after the treatment, which might be either a consequence of the decrease of the BAL neutrophils, or related to a possible antioxidant effect of the treatment. Lastly, the exercise-induced increase in plasma uric acid was significantly less marked after the treatment, which could be due to a systemic antioxidant effect of the hyaluronate.In conclusion, this preliminary study brings some evidence that hyaluronate could have some antiinflammatory and antioxidant effects at the pulmonary—and systemic—level in COPD horses in remission. However, it does not help to understand the possible mechanisms underlying these observations. Further studies are now necessary to better understand its action, to assess the effect of the product on the pulmonary function of horses suffering from other respiratory problems as well as to assess the efficiency of other ways of administration, i.e., nebulization.     

Influence of subclinical pulmonary findings on cardiac parameters in Icelandic horses

In the present study we examined, if in Icelandic horses an increase in heart and/ or breathing rate is physiological and breed dependend or a sign of a pulmonary or cardiac disease. Therefore we examined 37 Icelandic horses with the prereport of being healthy. During clinical lung examination four horses showed symptoms of a pulmonary disease like increased breathing rate and enforced breathing at rest. These horses were excluded from the study. The other 33 horses were clinically normal. 17 of these horses were unridden (untrained) and 16 horses were regularly worked (trained). After clinical examination in all horses analysis of arterial blood gas, endoscopy with tracheo- bronchial secret analysis and radiographic examination of the lung were carried out. Additionally electro- and echocardiographic examinations and standardised exercise tests with determination of heart and breathing rate as well as plasma lactate values were performed in all horses. During electro- and echocardiographic examination no pathological findings were observed. In total 22 of the 33 horses showed abnormal lung findings. Seven horses had mild signs of RAO and 15 horses had mild signs of interstitial bronchitis. Three horses had additional pulmonary haemorrhage. Eleven out of the 33 horses showed no abnormal lung findings. The breathing rate at rest differed not significantly between horses with (21 +/- 1/min) or without (23 +/- 2/min) pulmonary findings. The heart rate also did not differ significantly between horses with (39 +/- 1/min) or without (42 +/- 1/min) pulmonary findings. In contrast to this the trained Icelandic horses with abnormal pulmonary findings had significantly higher heart rates (p = 0.01) and significantly lower breathing rates (p = 0.009) compared to those without abnormal pulmonary findings. During echocardiography Icelandic horses with abnormal pulmonary findings had significantly larger left atrial diameter (without abnormal pulmonary findings: 82 +/- 7 mm, with abnormal pulmonary findings: 90 +/- 8 mm, p = 0.02). Compared to the untrained Icelandic horses (5.4 +/- 2 mmol/l) the trained horses showed significantly lower plasma lactate values (3.1 +/- 2 mmol/l, p = 0.001) immediately after exercise. After exercise the icelandic horses with abnormal pulmonary findings had significantly higher breathing rates (p < 0.05) and longer recovery periods (30 minutes) than horses without abnormal respiratory findings (15 minutes). Recovery of heart rate after exercise showed no differences between groups.     

Correlation of clinical score, intrapleural pressure, cytologic findings of bronchoalveolar fluid, and histopathologic lesions of pulmonary tissue in horses with summer pasture-associated obstructive pulmonary disease

OBJECTIVE: To correlate clinical score, intrapleural pressure, cytologic findings of bronchoalveolar lavage fluid (BALF), and histologic lesions of pulmonary tissue in horses affected with summer pasture-associated obstructive pulmonary disease (SPAOPD). ANIMALS: 8 adult horses affected with SPAOPD and 6 adult horses without evidence of respiratory tract disease. PROCEDURE: Clinical score, change in intrapleural pressure (deltaPpl) during tidal breathing, results of cytologic examination and bacteriologic culture of BALF, and results of histologic examination of pulmonary parenchyma were evaluated. RESULTS: Clinical scores for SPAOPD-affected horses (median, 5.75; range, 4.0 to 7.5) were significantly greater, compared with clinically normal horses (median, 2.0; range, 2.0 to 3.0). Cytologic examination of BALF from SPAOPD-affected horses revealed predominantly nondegenerate neutrophils. Histologic lesions were identified throughout pulmonary tissue and included severe accumulation of mucus and neutrophils within the small airways, metaplasia of bronchiolar goblet cells, and mild peribronchial infiltrate. Histologic examination of specimens collected via percutaneous biopsy was predictive of disease and corresponded to findings at postmortem examination. Clinical score and deltaPpl were highly correlated with mucus accumulation in the airways of affected horses. Peribronchial inflammatory infiltrate correlated with percentage of neutrophils in BALF of affected horses. CONCLUSIONS AND CLINICAL RELEVANCE: Clinical scoring and deltaPpl provided valid estimates of disease severity. Findings from cytologic examination of BALF of SPAOPD-affected horses varied, although, in most instances, it was diagnostically useful. Severe mucus accumulation in the airways was the most remarkable histopathologic finding in SPAOPD-affected horses. Examination of biopsy specimens collected from pulmonary parenchyma was consistently useful in diagnosing SPAOPD.     

Chronic obstructive pulmonary disease: Usefulness of clinical signs, bronchoalveolar lavage, and lung biopsy as diagnostic and prognostic aids

We examined 18 horses with clinical signs of chronic obstructive pulmonary disease (COPD) using physical examination, cytological and bacteriological evaluation of bronchoalveolar fluid, and percutaneous lung biopsy. In 16 cases, histological examination of lung tissue confirmed the diagnosis of COPD. Two horses were excluded: one had uncomplicated bacterial pneumonia and in the other a satisfactory lung biopsy could not be obtained. In horses with COPD, the most common historical complaint was coughing, which was reported in 88%. The most frequently detected abnormal finding on physical examination was abnormal lung sounds; these were detected in 69% of horses at rest and in 88% of horses breathing deeply into a bag. A novel finding was that 29% of horses had lung sounds that were quieter than would be expected for the degree of respiratory effort. Horses with COPD had increased percentages of neutrophils and decreased percentages of lymphocytes and macrophages in their bronchoalveolar lavage fluid. Bronchiolar neutrophil infiltration and peribronchiolar mast cell accumulation in lung biopsy tissue had the highest correlation with clinical condition. The severity of pathological changes in biopsies of lung did not predict whether the horse would die in the two to four year follow-up period. Horses that died in the follow-up period were more severely affected clinically at initial presentation than horses that were alive at the end of the follow-up period.     

A study of the effect of a platelet activating factor (PAF) receptor antagonist on antigen challenge of horses with chronic obstructive pulmonary disease

Antigen challenge involving exposure to straw and mouldy hay for 7 h produced lung function changes and neutrophil recruitment to the lungs in horses with chronic obstructive pulmonary disease (COPD). During the challenge, an increase in radiolabelled neutrophils in the lungs occurred, together with increased respiratory rate and pleural pressure. The role of platelet activating factor (PAF) in antigen-induced neutrophil accumulation, and increased pleural pressure and respiratory rate was investigated by administering the PAF receptor antagonist WEB 2086 to asymptomatic COPD horses prior to antigen challenge. WEB 2086 (3 mg/kg i.v.) did not affect antigen-induced changes in either neutrophil accumulation or respiratory function. These results suggest that PAF may not be an important mediator of the response to antigen in equine COPD.     

Safety and efficacy of a technique for thoracoscopically guided pulmonary wedge resection in horses

OBJECTIVE: To evaluate the safety and efficacy of thoracoscopically guided pulmonary wedge resection in horses. ANIMALS: 10 horses (5 control horses and 5 horses affected with recurrent airway obstruction [ie, heaves]). PROCEDURE: Each horse underwent a thoracoscopically guided pulmonary wedge resection. Before, during, and after surgery, heart rate, respiratory rate, arterial blood gases, and systemic and pulmonary arterial pressures were measured. Physical examination, CBC, and thoracic radiography and ultrasonography were performed 24 hours before and 2 and 48 hours after surgery. Pulmonary specimens were assessed by histologic examination. A second thoracoscopic procedure 14 days later was used to evaluate the resection site. RESULTS: The technique provided excellent specimens for histologic evaluation of the lung. Heart and respiratory rates decreased significantly after horses were administered sedatives. A significant transient decrease in Pao2 was detected immediately after pulmonary wedge resection, but we did not detect significant effects on arterial pH, Paco2, or mean arterial and pulmonary arterial pressures. All horses except 1 were clinically normal after thoracoscopic surgery; that horse developed hemothorax attributable to iatrogenic injury to the diaphragm. The second thoracoscopy revealed minimal inflammation, and there were no adhesions. CONCLUSIONS AND CLINICAL RELEVANCE: Thoracoscopically guided pulmonary wedge resection provides a minimally invasive method for use in obtaining specimens of lung tissues from healthy horses and those with lung disease. This technique may be useful for the diagnosis of diseases of the lungs and thoracic cavity.     

The presence of precipitating antibodies in the sera of horses with chronic obstructive pulmonary disease (COPD).

The sera of horses affected and not affected with chronic obstructive pulmonary disease (COPD) were examined for precipitins to Micropolyspora faeni and Aspergillus fumigatus. Precipitins to both antigens were not restricted to COPD cases but occurred more frequently in animals affected with COPD. Many animals without detectable precipitins responded clinically to inhalation challenge with these antigens.     

An investigation of the incidence of chronic obstructive pulmonary disease (COPD) in random populations of Swiss horses

The incidence of Chronic Obstructive Pulmonary Disease (COPD) in Switzerland was determined in three groups of horses selected at random. Group A (97 horses) and Group B (93 horses) had no history of respiratory disease, but Group C (113 horses) had a history of lower respiratory tract disease. All horses were examined by auscultation of the respiratory tract under forced breathing, endoscopic examination of the upper and lower respiratory tract, arterial blood gas analysis at rest and cytological examination of respiratory secretions (RS). Fifty-four per cent of the horses in Group A and 54.8 per cent of Group B were diagnosed as suffering clinical COPD and only 12.4 per cent of horses in Group A and 8.6 per cent in Group B had no detectable abnormalities in their lower respiratory tracts. In Group B, 19.4 per cent were considered to be suffering from parasitic pulmonary disease indicated by elevated numbers of eosinophils in their RS. Pharyngeal lymphoid hyperplasia was exhibited in 70.1 per cent of Group A and 74.2 per cent of Group B. Cytological examination of RS was useful to determine if the secretions found in the trachea originated from the upper or lower respiratory tract. Arterial blood gas analysis revealed no significant differences between healthy horses and those with subclinical or mild COPD.     

A study on the possible role of chymotrypsin in the aetiology of equine chronic obstructive pulmonary disease (COPD)

The chymotrypsin activity of seven batches of Micropolyspora faeni and of five batches of Aspergillus fumigatus culture extracts, prepared for inhalation challenge in horses, was assayed and was found to range between 0.29 and 1.45 units/mg protein and 0.02 and 0.20 units/mg protein respectively. Horses affected with chronic obstructive pulmonary disease (COPD) were challenged with two batches of each antigen which had different chymotrypsin activities and no significant correlations were found between the degree of response to challenge and the chymotrypsin activity of the antigens. Inhalation of two doses of nebulised, purified chymotrypsin over 4 days did not induce signs of respiratory disease in COPD-affected horses. However, repeated chymotrypsin inhalations after an interval of 3 weeks caused an exacerbation of signs of COPD in one horse. These studies suggest that, although repeated inhalation of purified chymotrypsin may induce respiratory hypersensitivity in horses, the chymotrypsin-like enzymes of M. faeni and A. fumigatus do not play a major role in the precipitation of clinical signs of equine COPD.     

Effect of antigen challenge on the activation of peripheral blood neutrophils from horses with chronic obstructive pulmonary disease

The effect of antigen challenge on the state of activation of peripheral blood neutrophils from horses with chronic obstructive pulmonary disease ( ) has been determined by measuring neutrophil superoxide anion formation. Prior to a seven-hour antigen challenge superoxide anion production by neutrophils from asymptomatic horses with and normal horses in response to platelet activating factor ( ) (with and without cytochalasin B), serum treated zymosan ( ) and phorbol myristate acetate ( ) was similar. Agonist-induced superoxide production by neutrophils from symptomatic and normal horses remained unchanged five and 24 hours after antigen challenge. Interestingly, however, superoxide production by neutrophils from symptomatic horses was significantly increased 24 hours after antigen challenge in the control samples for each agonist (basal superoxide production), a five-fold increase being measured in the presence of cytochalasin B. There was a small increase in superoxide production by neutrophils from normal horses but this only reached significance in one set of control samples. The change in activation state of circulating neutrophils during antigen challenge may facilitate the lung neutrophilia and subsequent tissue damage which occur in .     

Growth-related changes in the pulmonary function of goats

Growth-related changes in pulmonary function values were investigated in 20 healthy French Alpine goats, aged between 20 and 550 days, weighing 7–55 kg. Pulmonary ventilation, mechanics of breathing and arterial oxyten tension were measured using standardized techniques and methods adapted for goats of different body sizes. The Ppl values and the tI/tTOT ratio showed no significant changes with age and body size. The ventilation values (Vt, Ve, mVI and mVE) increased linearly with growth. There was a significant correlation of age and body weight with dynamic lung compliance (Cdyn), total pulmonary resistance (RL), viscous work of breathing (Wvis tot) and minute viscous work (Wvis min) throughout the age range studied. Cdyn, Wvis tot and Wvis min increased and RL decreased with age and body weight. Arterial blood gases (PaO₂ and PaCO₂) did not show significant changes over the age range studied. Regression equations for each pulmonary function parameter are given with body weight as the independent variable. Data for the mechanics of breathing were compared with those elsewhere for cattle, horses, man and dogs.