Topic:Asthma
Equine asthma, also known as equine recurrent airway obstruction (RAO) or heaves, is a chronic respiratory condition affecting horses. It is characterized by airway inflammation, mucus production, and bronchoconstriction, leading to clinical signs such as coughing, nasal discharge, and labored breathing. The condition is often exacerbated by environmental factors such as dust, mold, and pollen, which can trigger an immune response in susceptible horses. Equine asthma is managed through environmental modifications, medical treatments, and sometimes dietary adjustments to alleviate symptoms and improve respiratory function. This page compiles peer-reviewed research studies and scholarly articles that explore the pathophysiology, diagnosis, and management strategies of equine asthma.
Adenosine receptor modulation: potential implications in veterinary medicine. Adenosine is a purine nucleoside whose concentration increases during inflammation and hypoxia and the many roles of this molecule are becoming better understood. Increased reactivity to adenosine of the airways of asthmatic but not of normal subjects underlines the role of adenosine in airway inflammation. The identification and pharmacological characterisation of different adenosine receptors have stimulated the search for subtype-specific ligands able to modulate the effects of this molecule in a directed way. Several compounds of different chemical classes have been identified as having po...
Equine recurrent airway obstruction does not alter airway muscarinic acetylcholine receptor expression and subtype distribution. In recurrent airway obstruction (RAO) or heaves, bronchospasm has been attributed to enhanced cholinergic activity. However, the expression and function of muscarinic acetylcholine receptors (mAChR) and their signaling components are not yet known. Thus, we examined the expression, subtype distribution and postreceptor signaling pathways of mAChR in the peripheral lung, bronchial and tracheal epithelia with the underlying smooth muscle from nine horses with RAO and 11 healthy control horses. In RAO horses, no significant segment-dependent alteration in mAChR density and subtype distribution (a...
Relevance of using a human microarray to study gene expression in heaves-affected horses. Environmental causes of heaves are well described, but the molecular mechanisms of the disease remain unclear. Previous studies have highlighted the implications of variations in gene expression, most using reverse transcription polymerase chain reaction (RT-PCR). This well-known technique limits the number of genes that can be studied in a single assay. Microarray appears to be a valuable tool to by-pass this limitation, but so far there has been no equine-specific microarray available on the market. The present study was performed to determine whether a human microarray could be used to stud...
A region on equine chromosome 13 is linked to recurrent airway obstruction in horses. REASONS FOR STUDY: Equine recurrent airway obstruction (RAO) is probably dependent on a complex interaction of genetic and environmental factors and shares many characteristic features with human asthma. Interleukin 4 receptor a chain (IL4RA) is a candidate gene because of its role in the development of human asthma, confirmation of this association is therefore required. Methods: The equine BAC clone containing the IL4RA gene was localised to ECA13q13 by the FISH method. Microsatellite markers in this region were investigated for possible association and linkage with RAO in 2 large Warmblood ...
Genes and respiratory disease: a first step on a long journey. This review highlights the critical importance of phenotype definition in the understanding of the pathogenesis of respiratory disease in horses. The general approach to genetic studies is discussed and comparative studies of recurrent airway obstruction (RAO) conditions, such as asthma, described in the context of learning more about equivalent equine conditions. The availability of methods to study genetic tests have previously relied on DNA sequence knowledge from man, laboratory and domesticated animals, but recent data from the horse genome sequence are now available. This should facilita...
Early onset airway obstruction in response to organic dust in the horse. Equine recurrent airway obstruction (RAO) has been used as a naturally occurring model of human asthma. However, it is unknown whether there is an early-phase response in RAO. The aim of this study was to determine whether exposure to organic dust induces immediate changes in lung function in RAO-affected horses, which could be mediated by airway mast cells. Six RAO-affected horses in remission and six control horses were challenged with hay-straw dust suspension by nebulization. Total respiratory resistance at 1 Hz, measured by forced oscillation, was increased from 0.62 +/- 0.09 cmH(2)O.l(-1...
Theophylline does not potentiate the effects of a low dose of dexamethasone in horses with recurrent airway obstruction. Theophylline has been shown to have corticosteroid-sparing effects for the treatment of human asthma. A similar effect, if present in horses, would allow diminishing the dose of corticosteroids administered to equine patients with inflammatory airway diseases. Objective: To evaluate whether theophylline potentiates the effects of a low dose of dexamethasone when treating horses with recurrent airway obstruction (RAO). Objective: Theophylline has steroid-sparing effects in horses with RAO. Methods: Ten mature mixed breed horses in clinical exacerbation of RAO were studied. Using an incomplete c...
Platelets in equine recurrent airway obstruction. Platelets contribute to the pathogenesis of human allergic airway disease. The aim of this study was to compare platelet activating factor (PAF)-induced platelet aggregation and thromboxane (Tx) production, plasma Tx and 5-hydroxytryptamine (5-HT) in ponies with recurrent airway obstruction (RAO), an hypersensitivity to inhaled antigens, and normal ponies, before and after antigen exposure. Plasma 5-HT was significantly higher in ponies with RAO but was not further increased by antigen challenge. There was no difference between PAF-induced platelet aggregation or Tx production, or in plasma Tx...
cDNA cloning and substrate specificity of equine tryptase, a possible mediator in equine heaves. Mast cell mediators are believed to play a central role in inflammatory lung disorders such as human allergic and occupational asthma. Equine heaves is characterized by reversible neutrophilic airway inflammation and airway obstruction, primarily due to bronchospasm and mucus hypersecretion, following exposure of susceptible horses to organic stable dusts. As such, heaves shares many similarities with human occupational dust-induced asthma and therefore it is proposed that mast cells may also be implicated in the pathogenesis of heaves. Tryptase, a mast cell-specific proteinase, can be used as...
In vitro inhibition of matrix metalloproteinase activity in tracheal epithelial lining fluid from horses with recurrent airway obstruction. To evaluate inhibitory effects of synthetic matrix metalloproteinase (MMP) inhibitors in vitro on gelatinolytic and collagenolytic activities in tracheal epithelial lining fluid (TELF) of horses with recurrent airway obstruction (RAO). Methods: 10 horses with RAO and 5 healthy control horses. Methods: Substrate-based functional assays, collagen I and gelatin degradation, were used to measure endogenous collagenolytic and gelatinolytic activities in TELF. In vitro inhibition of MMP activity in TELF with 2 chemically modified tetracyclines (CMTs; CMT-3 and CMT-8) and 2 bisphosphonates (BPs; zole...
DNA binding activity of transcription factors in bronchial cells of horses with recurrent airway obstruction. Horses with recurrent airway obstruction (RAO) present many similarities with human asthmatics including airway inflammation, hyperresponsiveness, reversible obstruction, and increased NF-kappaB expression. Studies in experimental asthma models have shown that transcriptions factors such as activator protein-1 (AP-1), GATA-3, cyclic AMP response element binding protein (CREB) and CAAT/enhancer binding protein (C/EBP) may also play an important role in airway inflammation. The purpose of this study was to measure DNA binding activity of these transcription factors in the airways of horses with ...
Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling. Increased airway smooth muscle mass is a prominent feature of asthmatic airway remodeling. Airway smooth muscle hyperplasia occurs in rodent models of experimental asthma, but the relevance of such finding to spontaneously occurring disease in large mammals is unknown. Objective: We examined horses with heaves, a naturally occurring equine asthma related to sensitization and exposure to moldy hay. We hypothesized that airway remodeling occurs in heaves and shares disease mechanisms with asthma. Methods: We quantified the airway smooth muscle mass and the numbers of proliferating and apoptotic ...
The role of oxidative stress in an equine model of human asthma. Equine recurrent airway obstruction (RAO) is a naturally occurring respiratory disease in horses with many similarities to human asthma and, as a result, has been used as an animal model of this disease. Oxidative stress has been demonstrated to occur in a range of respiratory diseases in human beings including asthma. Quantitatively, horses have a greater non-enzymatic antioxidant capacity in the pulmonary epithelial lining fluid compared to human beings due to high ascorbic acid concentrations, which reflects their ability to synthesise ascorbic acid. Consequently, a greater oxidative load i...
Immunohistochemical determination of the expression of endothelin receptors in bronchial smooth muscle and epithelium of healthy horses and horses affected by summer pasture-associated obstructive pulmonary disease. To immunohistochemically determine the expression of endothelin (ET) receptors in bronchial smooth muscle and epithelium of healthy horses and horses affected by summer pasture-associated obstructive pulmonary disease (SPAOPD). Methods: Tissue specimens obtained from 8 healthy and 8 SPAOPD-affected horses. Methods: Horses were examined and assigned to healthy and SPAOPD groups. Horses were then euthanatized, and tissue specimens containing bronchi of approximately 4 to 8 mm in diameter were immediately collected from all lung lobes, fixed in zinc-formalin solution for 12 hours, and embedded in...
Improvement of the lung function of horses with heaves by treatment with a botanical preparation for 14 days. The effects of an oral preparation containing a mixture of extracts from yellow gentian, garden sorrel, cowslip, verbena and common elder on the lung function of nine horses suffering from heaves were determined in a longitudinal crossover study. The horses were divided at random into a group of five (group 1) and a group of four (group 2). The horses in group 1 were each given 15 tablets of the preparation twice daily, while the horses in group 2 were left untreated. Fourteen days later, the horses in group 2 were given the same course of treatment while the horses in group 1 were left untrea...
Direct activation of gelatinase B (MMP-9) by hay dust suspension and different components of organic dust. Matrix metalloproteinases (MMPs) are involved in tissue destruction in allergic airway diseases. We studied the ability of various allergenic substances to directly activate recombinant 92kDa proMMP-9. The substances included hay dust suspension (HDS) and its components (supernatant, particulate matter and wash fluid of particulate matter), storage mite extract and two Aspergillus fumigatus extracts. The allergen suspensions were incubated in vitro with proMMP-9. After incubation the conversion of proMMP-9 to 10kDa lower active forms were studied using gelatin zymography and Western immunoblot...
Immune sensitization of equine bronchus: glutathione, IL-1beta expression and tissue responsiveness. Increasing clinical epidemiological and experimental evidence indicates that excess of production of reactive oxygen free radicals (ROS) induced by an oxidative stress is involved in the pathogenesis of a number of human airway disorders, as well as equine recurrent airway obstruction. Free-radicals modulate the activation of transcription factors, such as nuclear factor-(NF)-kappaB and activator protein (AP)-1, in several different cells. This activation leads to expression of many pro-inflammatory cytokines, including interleukin (IL)-1beta. We have hypothesized that equine airway sensitizat...
Expression of interleukin (IL)-5 and IL-9 receptors on neutrophils of horses with heaves. Heaves, a condition associated with airway neutrophilia, is believed to result from an allergic response to environmental dust particles. However, the contribution of neutrophils to the allergic response is poorly understood. It has been hypothesized that Th2-type cytokines can directly activate neutrophils to produce pro-inflammatory mediators. The present study focused on the presence of receptors for the Th2-type cytokines interleukin (IL)-5 and IL-9 on peripheral blood neutrophils of horses with heaves. Neutrophils were isolated from peripheral blood of horses with heaves (n=7), and normal...
Respiratory mechanics in Standardbred horses with sub-clinical inflammatory airway disease and poor athletic performance. The aim of this study was to investigate and quantify respiratory mechanical dysfunctions in Standardbred horses with both poor performance and bronchoalveolar lavage fluid cytology characteristic of inflammatory airway disease (IAD). A control group of healthy Standardbred horses was compared. Respiratory mechanics and breathing pattern were examined at rest and during hyperventilation induced using a rebreathing method. At rest, respiratory mechanics and breathing pattern were superimposable in both groups. In IAD horses, rebreathing increased ventilation, with larger tidal volumes and lower...
Agonist-independent alteration in beta-adrenoceptor-G-protein-adenylate cyclase system in an equine model of recurrent airway obstruction. We examined the inhibitory sympathetic beta-adrenergic mechanisms in peripheral lung, bronchi and trachea of an equine model of recurrent airway obstruction (RAO), to support the hypothesis that the beta-adrenergic receptor dysfunction is not only restricted to cell surface receptor density but rather encompasses a mechanistic defect apart from the receptor, to the intracellular signaling components. The non-asthmatic lung possessed 3.2-fold more beta-adrenergic receptors than bronchi (496 +/- 19.4 vs. 155.1+/- 19.6 fmol/mg protein; P < 0.01) and 6.2-fold higher than in the trachea (79.8 +/...
Overexpression of eCLCA1 in small airways of horses with recurrent airway obstruction. The human hCLCA1 and murine mCLCA3 (chloride channels, calcium-activated) have recently been identified as promising therapeutic targets in asthma. Recurrent airway obstruction in horses is an important animal model of human asthma. Here, we have cloned and characterized the first equine CLCA family member, eCLCA1. The 913 amino acids eCLCA1 polypeptide forms a 120-kDa transmembrane glycoprotein that is processed to an 80-kDa protein in vivo. Three single nucleotide polymorphisms were detected in the eCLCA1 coding region in 14 horses, resulting in two amino acid changes (485H/R and 490V/L). Ho...
Chronic exacerbation of equine heaves is associated with an increased expression of interleukin-17 mRNA in bronchoalveolar lavage cells. Recent finding suggests that T-cells may be involved in the pathogenesis of heaves in horses. However, little is known concerning their possible contribution to pulmonary neutrophilia, a characteristic finding in heaves. Interleukin (IL)-17 is a cytokine secreted by activated T-cells that indirectly promotes the maturation, chemotaxis and activation of neutrophils. We therefore hypothesized that IL-17 may be involved in the recruitment of neutrophils into the airways and that its mRNA expression would be increased in bronchoalveolar lavage (BAL) cells of horses with heaves. Heaves susceptible ...
Cold weather exercise and airway cytokine expression. Athletes who perform repeated exercise while breathing cold air have a high prevalence of asthmalike chronic airway disease, but the mechanism linking such activity to airway inflammation is unknown. We used a novel animal model (exercising horses) to test the hypothesis that exercise-induced chronic airway disease is caused by exposure of intrapulmonary airways to unconditioned air, resulting in the upregulation of cytokine expression. Bronchoalveolar lavage fluid (BALF) was obtained from eight horses 5 h after submaximal exercise while they breathed room temperature or subfreezing air in a r...
The effects of a single acupuncture treatment in horses with severe recurrent airway obstruction. Acupuncture may be recommended for horses with 'heaves' because it is being increasingly applied to treat human asthma. Therefore, its efficacy was investigated in horses with this asthma-like disease. Objective: To evaluate the efficacy of a single acupuncture treatment for the relief of airway obstruction in heaves-affected horses. Methods: The efficacy of a single acupuncture treatment was tested in 10 heaves-affected horses, and the effect of removal from the dusty stall environment in 5 heaves-affected horses. Before treatment, horses were stabled to induce airway obstruction and, apart f...
Comparison of TGF-beta 1 concentrations in bronchoalveolar fluid of horses affected with heaves and of normal controls. Airway remodeling may play an important role in heaves pathophysiology. Transforming growth factor-beta 1 (TGF-beta1) is a potent profibrotic cytokine, which might contribute to airway wall thickening and fibrosis of bronchiolar and alveolar submucosa. An ELISA designed for the measurement of human TGF-beta1 was used to measured total TGF-beta1 released in bronchoalveolar lavage fluid (BALF) of normal horses and of those affected with heaves in remission. The specificity of the assay for TGF-beta1 of the horse was confirmed using recombinant equine TGF-beta1. The influence of hay exposure on T...
Proliferative aspects of airway smooth muscle. Increased airway smooth muscle (ASM) mass is perhaps the most important component of the airway wall remodeling process in asthma. Known mediators of ASM proliferation in cell culture models fall into 2 categories: those that activate receptors with intrinsic receptor tyrosine kinase activity and those that have their effects through receptors linked to heterotrimeric guanosine triphosphate-binding proteins. The major candidate signaling pathways activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase. Increases in ASM mass may also...
Application of the comet assay for investigation of oxidative DNA damage in equine peripheral blood mononuclear cells. Oxidative stress occurs when antioxidant defense mechanisms are overwhelmed by free radicals and may lead to DNA damage, which has been implicated in processes such as aging and diseases such as cancer. The two main techniques presently used to quantify DNA damage are measurement of 8-hydroxydeoxyguanosine and the Comet assay (also known as single-cell gel electrophoresis). The aim of this study was to apply the comet assay to equine peripheral blood mononuclear cells (PBMCs) and identify two conditions in which we hypothesized that oxidative DNA damage would be increased in PBMCs: aging and e...
Allergen challenge alters lymphocyte phosphodiesterase activity in horses with heaves. Heaves is an allergic airway disease in horses characterised by reversible airway obstruction, bronchial hyperresponsiveness and airway inflammation associated with a Th(2) response. Cyclic nucleotide-dependent signalling pathways can regulate lymphocyte function. In this study, we examined lymphocyte PDE activity comparing horses with heaves to healthy control animals. Total PDE activity and the effects of isoenzyme selective inhibitors were measured before, 5 and 24 h after the start of a 7 h allergen challenge. Allergen challenge had no effect on either total cAMP PDE activity or its inhibi...
Breath condensate hydrogen peroxide correlates with both airway cytology and epithelial lining fluid ascorbic acid concentration in the horse. The relationship between hydrogen peroxide (H2O2) concentration in expired breath condensate (EBC) and cytology of the respiratory tract obtained from tracheal wash (TW) or bronchoalveolar lavage (BAL), and epithelial lining fluid (ELF) antioxidant status is unknown. To examine this we analysed the concentration of H2O2 in breath condensate from healthy horses and horses affected by recurrent airway obstruction (RAO), a condition considered to be an animal model of human asthma. The degree of airway inflammation was determined by assessing TW inflammation as mucus, cell density and neutrophil ...
[Mite allergy in the domestic horse: experience of an equine veterinarian specializing in the field of allergy]. When medical history and clinical examination for a recurrent or chronic cough reveal the presence of perennial allergy, the practitioner would be advised to look for mites present in the horse's environment. He can propose this service to his clients.