The equine asthma model of airway remodeling: from a veterinary to a human perspective

Abstract

Human asthma is a complex and heterogeneous disorder characterized by chronic inflammation, bronchospasm and airway remodeling. The latter is a major determinant of the structure-function relationship of the respiratory system and is likely contributing to the progressive and accelerated decline in lung function observed in patients over time. Anti-inflammatory drugs such as corticosteroids are the cornerstone of asthma treatment. While their action on inflammation and lung function is well characterized, their effect on remodeling remains largely unknown. An important hindrance to airway remodeling as a major focus in asthma research is that the physiologic and clinical consequences of airway wall thickening and altered composition are not well understood. In this perspective, equine asthma provides a unique and ethical (non-terminal) preclinical model for hypothesis testing and generation. Severe equine asthma is a spontaneous disease affecting adult horses characterized by recurrent and reversible episodes of disease exacerbations. It is associated with bronchoalveolar neutrophilic inflammation, bronchospasm, excessive mucus secretion. Severe equine asthma is also characterized by bronchial remodeling, which is only partially improved by prolonged period of disease remission induced by therapy or antigen avoidance strategies. This review will focus on the similarities and differences of airway remodeling in equine and human asthma, on the strengths and limitations of the equine model, and on the challenges the model has to face to keep up with human asthma research.

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

“…Furthermore, the mouse does not have natural inflammatory or allergic pulmonary pathologies, so airway inflammation is usually induced by exposure to ovalbumin (OVA) or other aeroallergens. In contrast to naturally occurring human asthma, which is a chronic disease characterized by persistent inflammation and remodeling due to intermittent or continuous inhalation exposure to allergens resulting in chronic eosinophilic/neutrophilic inflammation (Aun et al, 2017;Bullone and Lavoie, 2019), the mouse model shows more acute (<3 months) inflammation and no remodeling. To circumvent this problem, systemic sensitization protocols and repeated exposures to allergens have been tried but the results obtained from different routes of systemic sensitization (subcutaneous injection, intraperitoneal injection or intranasal inhalation) and different allergens (OVA, fungi, Ascaris antigens, house dust mite, cockroach extracts), used alone or in combination, are difficult to compare and to interpret (Aun et al, 2017).…”

“…This remodeling can induce irreversible obstruction of airways and may be a consequence of chronic tissue inflammation and altered repair processes. Since function and structure are closely related, the hypothesis is that remodeling leads to loss of airway and lung function (Bullone and Lavoie, 2019).…”

“…In a good animal model, homology of genes regulating immune function is essential and the horse shares higher homology with man for IL2, IL23 , and IL17 , compared to the mouse ( Tompkins et al, 2010 ; Lange-Consiglio et al, 2019 ). However, the most interesting aspect of the horse as a model to study asthma is airway remodeling, although this is less marked and involves the bronchial tree more peripherally than in man ( Bullone and Lavoie, 2019 ). The remodeling can be completely reversed by appropriate corticosteroid treatment in both human patients and horses ( Bullone and Lavoie, 2019 ) and sequential biopsies can be collected from the same standing sedated horse without the imperative to sacrifice the animal as compared to the mouse ( Leclere et al, 2011 ).…”

Intradermal Testing Results in Horses Affected by Mild-Moderate and Severe Equine Asthma

“…Equine asthma (EA) is a syndrome including inflammatory, recurrent, and chronic lower airway disorders of adult horses, sharing several similarities with human asthma [1,2]. It is clinically characterized by airflow obstruction, mucus hypersecretion and airway hyperreactivity.…”

Recellularization of bronchial extracellular matrix with primary bronchial smooth muscle cells

“…Thus, in order to evaluate the behavior of airway smooth muscle (ASM) cells in the asthmatic airways, we aimed to decellularize an equine respiratory bronchus while maintaining its architecture and protein composition to allow recellularization by bronchial smooth muscle cells. Equine bronchi were studied as horses spontaneously develop an asthma-like condition that shares clinical and remodeling features with human asthma (Bullone and Lavoie, 2019) . Furthermore, it was shown in this model that ASM is increased, and only partially reversible even after 1 year of inhaled corticosteroids (Herszberg, et al, 2006, Leclere, et al, 2012.…”