Summer Pasture-Associated Obstructive Pulmonary Disease
Dorothy M. Ainsworth
■ Definition and Etiopathogenesis A condition clinically similar to RAO develops in mature horses in the southeastern United States that are kept outdoors on pasture.
It is called summer pasture-associated obstructive pulmonary disease (SPAOPD), pasture asthma, or more recently severe equine asthma. As with RAO, this new term applies to horses that are exhibiting clinical exacerbations or are in remission. Clinical signs typically occur in June through September when the weather is warm and humid1; clinical signs resolve partially or completely when the horse is removed from the pasture. Winter manifestations of the disease are uncommon. Clinical signs parallel increases in environmental fungal spore (basidiospore, Nigrospora, and Curvularia) and grass (Bermuda grass and Johnson grass) pollen counts,2 suggesting that aeroallergens (and potentially others) trigger the disease. SPAOPD has also been reported in horses in the United Kingdom, although some of those cases may represent horses with underlying RAO whose condition is exacerbated by hot weather and airborne particulates.3-6As with RAO, the immunopathogenesis of SPAOPD is uncertain. In one study, neither the total nor the antigenspecific IgE and IgG titers to certain fungi (Aspergillus spp., Cladosporium herbarum, Penicillium spp.), to thermophilic actinomycetes species (Faenia rectivirgula, Saccharomonospora viridis, Thermoactinomyces thalpophilus), or to the forage mite Lepidoglyphus destructor in the tracheal lavage fluid were increased in SPAOPD-affected horses relative to controls.7 Cytokine mRNA profiles in BAL cells and in peripheral blood mononuclear cells (PBMCs) isolated from SPAOPD-affected and control horses fail to provide consistent support for a polarized response. Increased IL-4 and IFN-γ copy number in BAL cells and PBMCs isolated from affected horses relative to controls was reported in one study.8 In another investigation by the same group,9 the gene expression of IFN-γ and IL-13 (but not IL-4) in BAL cells and peripheral blood lymphocytes isolated from symptomatic horses exceeded that of controls.
In a gene expression study of peripheral lung tissue isolated from affected and control horses,10 18 genes of known function were differentially expressed and found to be involved with lung protection, defense, mediation of proinflammatory or antiinflammatory responses, promotion of or protection from oxidative stress, cell recovery and repair, and mitogenesis. Of the 18 genes, only secretoglobin was downregulated in diseased horses—similar to what occurs in RAO horses.11-13 In addition to blocking phospholipase A2 activation, secretoglobin reduces IL-8-enhanced neutrophil chemotaxis. Venugopal also reported upregulation of eight genes that encode proteins associated with cell repair and proliferation10 involved in lung repair and airway remodeling, supporting histopathologic changes previously described in affected horses.14 Differential expression of immune cytokines (IL-4, IFN-γ, IL-17, TGF-β) was not reported in their transcriptome study of lung tissue.
Because of its role in the pathophysiology of human obstructive pulmonary disorders, investigators have also evaluated endothelin-1 (ET-1) concentrations in horses with SPAOPD. This 21-amino acid peptide induces bronchoconstriction; enhances mucus secretion; promotes DNA syntheses and cell proliferation in airway smooth muscle cells; and facilitates airway inflammation by upregulating IL-1, IL-4, IL-8, TNF-α, and IFN-γ expression.15,16 Compared with control horses, SPAOPD-affected horses have increased ET-1 protein concentrations in the venous blood, BAL, and pulmonary epithelial lining fluid.16 This finding, coupled with the observation that endothelin receptors A and B in the bronchial smooth muscle of affected horses are increased,15 suggests that ET-1 is just one of many mediators involved in the pathophysiology of SPAOPD.
■ Clinical Signs and Differential Diagnoses The clinical signs of SPAOPD are seasonal, reversible, and vary in severity.
As with RAO, initial signs can be subtle and include exercise intolerance, intermittent cough, intermittent nasal discharge (serous or mucoid), and tachypnea. Horses are afebrile. As the disease progresses, accentuated expiratory efforts (heave line), nostril flaring, frequent coughing, and even respiratory distress can occur.1 Crackles, wheezes, and “silent areas,” suggesting the absence of air movement, may be auscultated.1,14 Differential diagnoses include bacterial, viral, or fungal respiratory infections (ruled out by evaluation of blood work and culture and examination of tracheal aspirates) and anhidrosis (ruled out by assessing sweat production in affected animals).■ Diagnosis Historical and physical examination findings, along with the temporal development of clinical signs, support the diagnosis of SPAOPD. As with RAO, endoscopy of the lower respiratory tract reveals an accumulation of mucopurulent exudate within the tracheobronchial tree, evidence of bronchial epithelial hyperemia and dynamic collapse of intrathoracic airways during expiration. Cytologic analysis of BAL fluid demonstrates neutrophilia (>25%), the absence of intracellular bacteria, and excessive mucous production.14 Microbial culture of pulmonary secretions is typically negative. Thoracic radiographic examination may reveal mild to moderate bronchointerstitial patterns with evidence of lung field hyperexpansion (flattened diaphragm). Ultrasonographic findings, although not specifically described in SPAOPD-affected horses, would be expected to be similar to those in horses with RAO. Postmortem examination of the lungs from affected horses reveals overinflation, the presence of rib impressions, and a failure to collapse. Histopathologic changes include accumulation of mucus and neutrophils in the small airways, peribronchiolar smooth muscle hypertrophy, peribronchiolar submucosal fibrosis, epithelial hyperplasia, goblet cell hyperplasia or metaplasia, and peribronchial neutrophilic and lymphocytic infiltrates, similar to RAO.
There is usually minimal evidence of emphysema and fibrosis.14,17 Collectively these changes represent airway remodeling similar to what occurs in RAO.■ Treatment The most important management change to implement is to move the horse from the offending pasture either to another pasture or to a cool, dust-free stall that is bedded with shavings. Hay should be moistened or steamed and fed to the horse from the ground to reduce inhalation of organic dusts. When stalls and barn areas are being cleaned, the horse should be removed from these areas. Medical therapies include administration of glucocorticoids and bronchodilators, as described for horses with RAO (see the Treatment and Prognosis section for RAO).
■ Prognosis Recurrence of the condition is likely to develop when susceptible horses are exposed to environmental triggers. Longitudinal studies have not been performed to ascertain the risk of permanent (irreversible) lung remodeling in recurring cases. The heritability of SPAOPD has not been established.