Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?

Abstract

Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is commonly used to evaluate the severity of local inflammation in the lung. Other mediators of inflammation, like interleukins involved in the chemotaxis of neutrophils, have been studied. Chronic obstructive pneumopathies lead to remodeling of bronchial walls and lung parenchyma, ultimately causing fibrosis. Matrix metalloproteinases (MMPs) are discussed as the most important proteolytic enzymes during remodeling in human medicine and increasing evidence exists for the horse as well. A systemic involvement has been shown for severe equine asthma by increased acute phase proteins like serum amyloid A and haptoglobin in peripheral blood during exacerbation. Studies focusing on these and further possible inflammatory markers for chronic respiratory disease in the horse are discussed in this review of the literature.

Modeling asthma: Pitfalls, promises, and the road ahead

“…A milder form of RAO, identified as “IAD” is characterized by nasal discharge and decreased performance, but horses with IAD display no increased respiratory effort at rest. In IAD, mixed/neutrophilic and eosinophilic inflammation may be present . Similar to human asthma, RAO and IAD respond to beta‐adrenergic agonists in combination with inhaled or systemic corticosteroids …”

G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

“…Reports using models of Drosophila melanogaster (Roeder et al, 2009), canines (Padrid, 1992;Zosky and Sly, 2007), felines (Norris Reinero et al, 2004), rats (Kucharewicz et al, 2008), equines (Herszberg et al, 2006), sheep (Zosky and Sly, 2007;Scheerlinck et al, 2008), guinea pigs (Canning and Chou, 2008), nonhuman primates (Coffman and Hessel, 2005), and mice (Zosky and Sly, 2007;Nials and Uddin, 2008;Chapman et al, 2014;Aun et al, 2017) can be found in the literature. Although felines and equines spontaneously display asthma-like symptoms, 1% of cats develop eosinophilic bronchitis (Padrid, 2000;Aun et al, 2017), and horses develop heaves resulting from moldy hay (Barton and Gehlen, 2016); they are not financially viable models for asthma research. Despite the physiologic compatibility of cats and horses, as well as guinea pigs, and nonhuman primates compared with mice, the diminished feasibility based on costs, transgenic resources, and other factors has made mice the gold standard for models of asthma (Zosky and Sly, 2007;Nials and Uddin, 2008;Chapman et al, 2014;Aun et al, 2017).…”

Leukotriene B4 in equine asthma syndrome: what do we know so far?

“…According to Barton & Gehlen (2016), disorders of the respiratory system are the most frequently diagnosed conditions in sport horses evaluated for poor performance, particularly in the lower airways such as equine recurrent airway obstruction (RAO) and inflammatory airway disease (IAD).…”

“…Since the use of fiber-optic endoscopy was first described in horses, cytological and microbiological evaluation of BALF have become the pillars in the diagnosis of respiratory disease alongside clinical and functional examinations (Barton & Gehlen 2016). Although severely asthmatic horses often show easily visible clinical signs of disease, difficulties may arise in clinical practice due to the fact that patients may be presented in remission.…”

“…The immunologic background of severe equine asthma remains not fully elucidated despite many studies on the pathogenesis and the therapeutic approach to exacerbation. Therefore, multiple studies have been performed to establish further inflammatory markers for equine respiratory diseases, but there are no data on the role of LTB4 in these diseases yet (Barton & Gehlen 2016).…”