Le souffle...               

Connue sous les noms d’emphysème pulmonaire, bronchite chronique, COPD (MPOC) équin et maladie des petites voies respiratoires, on préfère maintenant les termes « souffle » (Heaves, ou Recurrent Airway Obstruction (RAO) en anglais) pour décrire cette condition incurable des chevaux adultes (généralement ayant sept ans ou plus) associée à une obstruction respiratoire chronique dans laquelle des périodes de détresse respiratoire au repos sont notées. Certains chevaux développent plutôt des signes cliniques alors qu’ils sont au pâturage; on parle alors de Summer Pasture Associated Pulmonary Obstructive Disease (SPAOPD). Nous avons récemment proposé de plutôt utiliser le terme "asthme équin", à cause des nombreuses similitudes avec l'asthme de l'humain. 

L'asthme est une affection pulmonaire débilitante et chronique de l'homme, qui se caractérise par une difficulté respiratoire et une perte accélérée de la capacité pulmonaire des sujets affectés. On estime qu'il affecte environ 300 millions d'individus mondialement et que 250 000 décès sont attribuables annuellement à cette maladie. Des estimations conservatrices indiquent que 8 % de la population adulte canadienne et 12 % des enfants sont atteints d'asthme et que son incidence est grandissante. L’objectif de notre programme de recherche aux IRSCs est d'explorer la relation existante entre l’inflammation asthmatique chronique et les lésions pulmonaires (remodelage) qui y sont associées, dans le but d'identifier de nouvelles thérapies capables d'arrêter la progression de l'asthme de l'homme et du cheval, voir à renverser les changements établis.



La maladie inflammatoire des voies respiratoires profondes ou IAD...      

L’Inflammatory Airway Disease (IAD) est utilisée pour décrire une condition dont les signes respiratoires sont moins sévères avec absence de détresse respiratoire au repos. La majorité des chevaux connaîtront des épisodes transitoires d’IAD durant leur vie, avec une progression vers le souffle, ce qui est observé chez environ 15 % des chevaux. Cette condition correspond à la forme légère et modérée de l'Asthme Équin.


Le souffle, le SPAOPD et l’IAD ne sont pas des maladies différentes, mais bien des syndromes complexes résultant possiblement de phénomènes inflammatoires variés menant à des signes cliniques similaires, mais de sévérités variables.



Heaves, Severe Equine Asthma

It has been known (for many years) since antique time that horses develop a chronic and debilitating "asthma"-like disease when stabled and exposed to hay.  Many names have been used to describe this condition over the years (Heaves, equine COPD, Equine emphysema, Recurrent Airway obstruction ...), which can lead to confusion.  Furthermore, some horses will rather develop these clinical signs when on pasture (Summer Pasture Associated Obstructive Pulmonary Disease), suggesting that different antigens may contribute to the disease.  We have recently proposed to use the term "Equine Asthma" because of the similarities with human asthma, both in terms of the natural history of the disease, the clinical presentation, and the response to therapy.

Human asthma is the most common chronic inflammatory diseases of the respiratory tract affecting 300 million people globally, and 2 million Canadians. The hallmarks of the disease are airway inflammation and remodeling. Despite development of effective therapy to control inflammation, asthma remains incurable.


Mild/Moderate Equine Asthma or Inflammatory Airway Disease  (IAD)

IAD, or Inflammatory Airway Disease, is a term used to describe a non-infectious disease of the small airways in the horse. It is a highly prevalent disease in the equine species. IAD is a less severe form of asthma (Mild and Moderate Equine Asthma) with no respiratory distress at rest. The majority of horses will experience transient episodes of IAD in their lifetime, with an increase to the breath, which is observed in about 75% of horses at some point during their lifetime.



    Three main research programs:

Airway remodeling and its reversibility 


Airway remodeling occurs in horses with long-term, unresolved inflammation caused by recurrent airway obstruction (RAO), the disease commonly known as heaves. Is it possible to reverse this negative effect in horses? In human asthma, repeated exposure to environmental allergens leads to persistent inflammation and damage (remodeling) of the lungs, and a progressive loss of airway function. We have recently shown that a 12 months administration of inhaled corticosteroids, a common anti-asthma medication, alone or combined with a decrease antigen exposure, only partially reverse the asthmatic airway remodeling. Dr Lavoie's studies aim to determine if the reversibility of the asthma lung lesions can be potentiated and accelerated by the use of combined anti-asthma therapies and if so, to identify the cells and the mediators responsible for these changes. 

Dr. Jean-Pierre Lavoie answers the question of whether airway remodeling is reversible in horses with heaves.

Video http://www.thehorse.com/videos/34128/airway-remodeling-in-heaves


Contribution of neutrophils to allergic inflammation

Neutrophils are the predominant cells present in the airways of horses with heaves and  is also frequently present in the airways of serve human asthma.  In both conditions, neutrophils are insensitive to the administration of corticosteroids, the most common anti-asthma medication. This lead us to investigate the contribution of neutrophils to allergic inflammation and its response to corticosteroids.


Inflammatory Airway Disease (IAD) - inflammation and remodeling

IAD is the term commonly used to describe mild to moderate Equine Asthma.  It is associated with clinically variable intensities, and by definition, dyspnea at rest is not observed in affected horses. Similarly to human asthma, eosinophils, mast cells, and neutrophils may be found in the airways in IAD. Currently, the remodeling processes affecting the airways of these horses, and its relationship to severity and inflammation is largely unknown. Our program aims at blood biomarkers to identify horses with mild to moderate asthma that will eventually develop heaves, and therapy to stop this progression.



Current projects 

#1 PhD project - Selma Ben Hamouda 

In asthmatic subjects (as humans as horses), major changes occur principally in the extracellular matrix (ECM) and in the airway smooth muscle (ASM). As the ECM deposition in type I and type III collagen and in elastin increases and the ASM cells become more proliferative and show a secretory and migratory profiles.The aim of this study is to characterize the contribution of the ECM in the phenotypic modifications of the ASM cells observed in asthma by searching in different combinations of normal and asthmatic ASM cells and matrix and studying the morphologic and proliferative changes and the expression of the contractile proteins and the transcription factors of the ASM cells in each combination.We expect that the asthmatic ECM will increase the proliferative phenotype of the normal ASM cells and even reveal their migratory and secretory profiles. These modifications will be even more significant with asthmatic ASM cells.

Supported by CIHR



#2 Post-doctoral project  - Mohamed Issouf

Due to its contractile properties, smooth muscle cells have a central role in bronchospasm-induced airway obstruction. Our group had recently reported that the fast contracting myosin isoform is overexpressed in the equine asthmatic airways. Deciphering the regulation of the expression levels of myosin heavy chain 11 gene (myh11) and its isoforms would represent a major step for understanding the triggers and pathways leading to airway smooth muscle contraction in equine lung diseases. Therefore, one of our lines of research tried to elucidate the molecular mechanisms regulating the mRNA expression of smooth muscle myosin heavy chain and the overexpression of the SMB isoform in horses in order to identify new therapeutic target.

Supported by CIHR

#3 Post-doctoral project - Amandine Vargas

Neutrophils infiltrate the airways of asthmatic patients of all severities, yet their role in the pathogenesis of asthma and their contribution to airway remodeling is largely unknown. In this post-doctoral project, we hypothesized that neutrophils present in the airways of asthmatic patients modulate airway smooth muscle (ASM) proliferation by releasing bioactive exosomes. While not yet reported to be secreted by neutrophils, these newly discovered nano-sized vesicles have the capacity to modulate immune responses, cell migration, cell differentiation, and other aspects of cell-to-cell communication. The aim of this study is to determine whether exosomes are released by neutrophils, and if so, characterize their proteomic profile, and evaluate their capacity to modulate ASM cell proliferation.

Supported by NSERC

#4 Post-doctoral project - Alexandra Jochmans-Lemoine

Asthma is the most common chronic inflammatory lung disease worldwide. It is caused by a bronchial hypersensitivity to exogenous stimuli leading to bronchoconstriction, airway inflammation and remodelling. Unfortunately, if the symptoms of the disease are well characterized and for the most part well controlled, up until today, research was unable to find a cure for asthma. Assessing lung tissues in vivo in asthmatic patients is very difficult and invasive. More recently, advances in engineered tissue, has proven to be a great tool to understand diseases from a cellular to an organ level before assessing the pathology in animal models. In collaboration with Dr. Francine Goulet, we undertook to create a tissue-engineered bronchus alternative that would closely resemble natural airways. The 3D tri-layered bronchus combines smooth muscle, fibroblasts and epithelial cell layers. In our cellular model, we will first use horse tissues as this specie has the unique particularity to display a spontaneous disease called “heaves” presenting clinical signs very similar to those seen in human asthmatic patients. We are confident that this unique 3D tri-layered bronchus will help understand cellular communications responsible for airway remodelling in asthma and we propose to use it as a primary model to test allergens as well as treatments before using animal models

Supported by CIHR

#5 Master project - Amandine Bessonnat




Supported by Le Fonds de Recherche en Santé Équine

#6 Master project - Mireille Godbout

The project focuses on better understanding the mechanisms underlying the recruitment of equine neutrophils and, more specifically, to define the role of interleukin-4 (IL-4) in this response. An in vivo subcutaneous model incorporating the protein matrix Corning Matrigel ™ Matrix as a vehicle for cytokines was developed. We were able to study the migration of inflammatory cells in response to different concentrations of IL-4 and various incubation times. The matrices were harvested by biopsy and neutrophil infiltration quantified using a histological grade as well as flow cytometry.

Supported by NSERC


#7 Residency project  - Sophie Mainguy-Seers 

Several studies describe the therapeutic effects of azithromycin, an antibiotic from the macrolide family, in the treatment of severe neutrophilic human asthma. This molecule has anti-inflammatory and immunomodulation properties that improve pulmonary inflammation and respiratory functions in asthmatic patients. Our goal is first to determine if those beneficial effects are present in heaves-affected horses, and if so the molecular pathways associated with these findings.

Supported by Le Fonds de Recherche en Santé Équine


#8 Residency project - Clémentine Gy

Inflammatory Airway Disease (IAD), or mild to moderate Equine Asthma, is a highly prevalent non-infectious disease of the small airways in the horse. Currently, the diagnosis is based on the presence of lower airway inflammation using bronchoalveolar lavage fluid cytology, or an altered lung function. However, because neither of these techniques is commonly performed in the field, this common cause of exercise intolerance that may progress to Severe Equine Asthma is largely unrecognized in the horse population. The development of  biomarkers would facilitate the recognition of this condition. Five blood biomarkers will be evaluated on IAD or control horses with various unrelated inflammatory conditions to determine their capacity and specificity for IAD diagnosis.

Supported by Le Fonds de Recherche en Santé Équine



Laboratoire de Recherche sur l'Asthme Équin- Equine Asthma Research Laboratory



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