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.
Association between cough and cytology of bronchoalveolar lavage fluid and pulmonary function in horses diagnosed with inflammatory airway disease. The objective of this study was to examine the relationship between chronic cough, pulmonary mechanical function, bronchial hyper-responsiveness, and peripheral airway inflammation in adult performance horses with nonseptic inflammatory airway disease (IAD). Objective: We hypothesized that horses with a presenting complaint of cough have a higher percentage of inflammatory cells on bronchoalveolar lavage (BAL), greater airway obstruction, and airway hyper-responsiveness (AHR) than do horses without cough. ANIMALS/SAMPLE POPULATION: Adult performance horses (n = 137) referred for evaluation of ...
Increased mucus accumulation in horses chronically affected with recurrent airway obstruction is not associated with up-regulation of CLCA1, EGFR, MUC5AC, Bcl-2, IL-13 and INF-gamma expression. The mechanisms leading to mucus accumulation in equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) are unclear. In airways of human patients with asthma and/or chronic obstructive pulmonary disease as well as in animal models of these diseases, associations of mucus hyperproduction with increased calcium-activated chloride channel 1 (CLCA1), epidermal growth factor receptor (EGFR), mucin 5AC (MUC5AC), B-cell lymphoma 2 (Bcl-2), interleukin (IL)-13 and interferon (IFN)-gamma expression have been reported. We hypothesized that increased mucus accumulation in RAO and ...
Effects of neuraminidase on equine isolated bronchi. It has been demonstrated in mammals that the airway hyper-responsiveness, which accompanies viral infections, is the result of increased reflex bronchoconstriction due to inhibition of muscarinic prejunctional receptors, which belong to M2 subtypes. Multiple mechanisms account for virus-induced M2 receptor dysfunction. Viral neuraminidase may deglycosylate the M2 receptor, decreasing acetylcholine affinity. Equine influenza remains a common viral respiratory disease of horses worldwide, which results in loss to the equine industry, by decreasing performance, convalescence time and loss of peak...
Partial divergence of cytokine mRNA expression in bronchial tissues compared to bronchoalveolar lavage cells in horses with recurrent airway obstruction. The aim of this study was to investigate mRNA levels of cytokines in bronchial epithelium in horses with recurrent airway obstruction (RAO) during acute crisis and remission. Additionally, cytokine mRNA levels in endobronchial biopsies and bronchoalveolar lavage (BAL) cells were compared. Seven RAO horses were examined while in respiratory crisis following provocation and again while in remission after 2 months on pasture, during which time six healthy horses on pasture were also examined. Quantitative real-time PCR (RT-PCR) was used to assess mRNA expression for cytokines IL-5, IL-6, IL-8, IL...
Equine recurrent airway obstruction and insect bite hypersensitivity: understanding the diseases and uncovering possible new therapeutic approaches. Recurrent airway obstruction (RAO) and insect bite hypersensitivity (IBH) are allergic conditions that are commonly encountered in the horse. Whilst complete allergen avoidance is an effective management strategy for both diseases, this may not be achievable in all cases and treatment options are therefore required. The inflammatory response is the main therapeutic target for glucocorticoids given to horses with RAO and severe cases of IBH, whilst the bronchodilators used in RAO primarily target airway smooth muscle. Such drugs are effective in most but not all individuals and there may be unw...
Organic dust exposure increases mast cell tryptase in bronchoalveolar lavage fluid and airway epithelium of heaves horses. Mast cell degranulation is believed to act as a key event in initiating and maintaining airway response to allergen challenge in human asthma. It is hypothesized that the mast cell may play a similar role in equine heaves, which shares many similarities with occupational dust-induced asthma. Objective: The aim of this study was to quantify the mast cell proteinase tryptase in bronchoalveolar lavage fluid (BALF) from control and heaves-susceptible horses and to investigate tryptase mRNA and protein expression in pulmonary mast cells. Methods: Equine BALF tryptase concentrations were determined ...
Lung function and airway cytologic profiles in horses with recurrent airway obstruction maintained in low-dust environments. The effects of long-term environmental management on airway obstruction and inflammation in horses with recurrent airway obstruction (RAO) are unknown. Objective: Horses with RAO maintained in low-dust environments have persistent airway obstruction and neutrophilic inflammation. Methods: Study horses were treated for RAO and then maintained in low-dust environments with no medical management. Horses were classified into 3 groups by years after diagnosis: 1 year (time 1, n = 9), 2-3 years (time 2, n = 7), and 5-6 years (time 3, n = 8). The comparison groups were age-matched healthy horses. Met...
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...