Recurrent Airway Obstruction (RAO) is a chronic respiratory condition in horses characterized by airway inflammation, bronchoconstriction, and mucus accumulation. It is often triggered by exposure to environmental allergens such as dust, mold, and pollen. Horses with RAO exhibit symptoms including coughing, nasal discharge, and labored breathing, particularly during exercise or in dusty environments. The condition is comparable to asthma in humans and can significantly impact a horse's respiratory function and performance. This page compiles peer-reviewed research studies and scholarly articles that explore the pathophysiology, diagnosis, management, and treatment of Recurrent Airway Obstruction in equine populations.
Berndt A, Derksen FJ, Venta PJ, Karmaus W, Ewart S, Yuzbasiyan-Gurkan V, Robinson NE.Airway inflammation in recurrent airway obstruction (RAO) is triggered by housing affected horses in stables.It has been suggested that RAO is an allergic condition, but innate immune mechanisms are also involved. Fungal products activate innate immune mechanisms through toll-like receptor 2 (TLR2). In human airway epithelium, TLR2 activation leads to interleukin (IL)-8 production. This pathway is negatively regulated by the zinc finger protein A20. This study was performed to enhance understanding of innate immune mechanisms in RAO. Objective: TLR2 and IL-8 mRNA are elevated in RAO during sta...
Dunkel B, Rickards KJ, Werling D, Page CP, Cunningham FM.Recurrent airway obstruction (RAO) in mature horses is characterized by reversible airway obstruction and neutrophilic inflammation; there is also functional activation of circulating platelets and neutrophils. This study was undertaken to determine if changes in activation marker expression and heterotypic aggregate formation can be used as an indicator of this increased functional responsiveness. In vitro conditions for flow cytometric measurement of CD13, CD41/61 and CD62P expression on activated cells and heterotypic aggregate formation were established. Values were then compared before an...
Katavolos P, Ackerley CA, Viel L, Clark ME, Wen X, Bienzle D.Horses are prone to recurrent airway obstruction (RAO), an inflammatory lung disease induced by repeated exposure to environmental mold, dust, and bacterial components. Active disease manifests with mucus hyperproduction, neutrophilic inflammation, bronchoconstriction, and coughing. Chronically affected animals have lung remodeling characterized by smooth muscle hyperplasia, collagen deposition, lymphoid hyperplasia, and impaired aerobic performance. Clara cell secretory protein (CCSP) counters inflammation in the lung, hence we hypothesized that CCSP depletion is a key feature of RAO in horse...
Ainsworth DM, Matychak M, Reyner CL, Erb HN, Young JC.To examine effects of in vitro exposure to solutions of hay dust, lipopolysaccharide (LPS), or beta-glucan on chemokine and cell-surface receptor (CSR) gene expression in primary bronchial epithelial cell cultures (BECCs) established from healthy horses and horses with recurrent airway obstruction (RAO). Methods: BECCs established from bronchial biopsy specimens of 6 RAO-affected horses and 6 healthy horses. Methods: 5-day-old BECCs were treated with PBS solution, hay dust solutions, LPS, or beta-glucan for 6 or 24 hours. Gene expression of interleukin (IL)-8, chemokine (C-X-C motif) ligand 2 ...
Treonze KM, Alves K, Fischer P, Hagmann WK, Hora D, Kulick A, Vakerich K, Smith ND, Lingham RB, Maniar S, Reger TS, Zunic J, Munoz B, Prasit P....The purpose of this study was to characterize the alpha(4)beta(1) receptor (CD49d/CD29, very late antigen-4, VLA-4) on circulating equine leukocytes and to evaluate the intrinsic potency of an alpha(4)beta(1) receptor antagonist (Compound B) in the horse. Ultimately, these studies would allow us to determine the suitability of treating recurrent airway obstruction (RAO; heaves) affected horses by blocking the cellular recruitment of lymphocytes and neutrophils into the lung. The data demonstrates the alpha(4)beta(1) integrin is present on horse lymphocytes and neutrophils (fluorescence-assiste...
Reid CJ, Thompson L, Donnelly S, Deaton CM, Marlin DJ, Carrington SD, Irwin JA.Recurrent airway obstruction (RAO) is a chronic inflammatory condition in equine lung, which may share a common immunological basis with human asthma, in which dysregulated Th2 responses occur. Mammals express chitinases and chitinase-like proteins, two of which are active enzymes, chitotriosidase and acidic mammalian chitinase (AMCase). Both enzymes are upregulated in a range of inflammatory conditions, including asthma. We investigated the activity of chitinase in bronchoalveolar lavage fluid from horses with and without RAO in response to organic dust challenges. No significant differences ...
Lavoie JP, Thompson D, Hamilton E, Debrue M, David F, Hickey G.It has been suggested that many of the beneficial effects of corticosteroids are mediated through mitogen-activated protein kinase (MAPK) p38 inhibition. Objective: To investigate the efficacy of the MAPK p38 inhibitor compound MRL-EQ1 to either prevent (Phase 1) or treat (Phase 2) recurrent airway obstruction (RAO) in horses. Methods: MRL-EQ1 was administered i.v. at a dosage of 0.75-1.5 mg/kg bwt q. 12 h. In Phase 1, susceptible horses in clinical remission were divided into 2 groups (n = 5/group), based on historical values of respiratory mechanics. All horses were entered in the study in p...
Camargo FC, Robinson NE, Dirikolu L, Berney C, Eberhart S, Derksen FJ, Lehner AF, May J, Hughes C, Tobin T.Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroS...
Tahon L, Baselgia S, Gerber V, Doherr MG, Straub R, Robinson NE, Marti E.Recurrent airway obstruction (RAO) is a common condition in stabled horses characterised by small airway inflammation, airway neutrophilia and obstruction following exposure of susceptible horses to mouldy hay and straw and is thus regarded as a hypersensitivity reaction to mould spores. However, the role of IgE-mediated reactions in RAO remains unclear. The aim of the study was to investigate with a serological IgE ELISA test (Allercept), an in vitro sulfidoleukotriene (sLT) release assay (CAST) and with intradermal testing (IDT) whether serum IgE and IgE-mediated reactions against various mo...
Polikepahad S, Haque M, Francis J, Moore RM, Venugopal CS.The purpose of the study was to determine and compare the expression of endothelin (ET) receptors in the peripheral lungs of healthy horses and those affected with recurrent airway obstruction (RAO) using reverse transcriptase polymerase chain reaction (RT-PCR), real-time PCR, Western blot analysis, and immunohistochemical techniques. Two groups of horses (7 healthy and 7 RAO-affected) were selected from a pool of horses destined for euthanasia. The grouping of horses was based on the history, clinical scoring, and pulmonary function testing. After euthanasia, gross postmortem evaluation of th...
Christmann U, Welles EG, Waldridge BM, Schumacher J, Grier BL, Hite RD.Abnormalities in lung surfactant are well described in human respiratory diseases including asthma, but are poorly described in horses. Objective: Lung surfactant is abnormal in horses with clinical signs of recurrent airway obstruction (RAO). Methods: Six healthy horses and 5 horses with RAO. Methods: Bronchoalveolar lavage fluid (BALF) was obtained from all horses by standard procedures. Cell-free BALF was separated into crude surfactant pellets (CSP) and supernatant via ultracentrifugation. Phospholipid and protein content was analyzed from both of these fractions. Phospholipid composition ...
Gerber V, Swinburne JE, Blott SC, Nussbaumer P, Ramseyer A, Klukowska-Rötzler J, Dolf G, Marti E, Burger D, Leeb T.Recurrent airway obstruction (RAO) is a multifactorial and polygenic disease. Affected horses are typically 7 years of age or older and show exercise intolerance, increased breathing effort, coughing, airway neutrophilia, mucus accumulation and hyperreactivity as well as cholinergic bronchospasm. The environmental factors responsible are predominantly allergens and irritants in haydust, but the immunological mechanisms underlying RAO are still unclear. Several studies have demonstrated a familiar predisposition for RAO and it is now proven that the disease has a genetic basis. In offspring, th...
Marti E, Gerber V, Wilson AD, Lavoie JP, Horohov D, Crameri R, Lunn DP, Antczak D, Björnsdóttir S, Björnsdóttir TS, Cunningham F, Dérer M....Allergic diseases occur in most mammals, although some species such as humans, dogs and horses seem to be more prone to develop allergies than others. In horses, insect bite hypersensitivity (IBH), an allergic dermatitis caused by bites of midges, and recurrent airway obstruction (RAO), a hyperreactivity to stable born dust and allergens, are the two most prevalent allergic diseases. Allergic diseases involve the interaction of three major factors: (i) genetic constitution, (ii) exposure to allergens, and (iii) a dysregulation of the immune response determined by (i) and (ii). However, other e...
Gehlen H, Oey L, Rohn K, Bilzer T, Stadler P.Chronic pulmonary diseases (recurrent airway obstruction [RAO]) have been reported to alter skeletal muscle cells in humans. The purpose of this study was to evaluate a potential relationship between pulmonary and muscle variables in horses with a clinical diagnosis of RAO. Muscle biopsies from healthy horses and from horses with RAO were investigated and the relationship between the severity of lung disease and the degree of muscular changes was determined. Objective: We hypothesized that chronic pulmonary disease can lead to changes of the skeletal muscle in horses. Methods: Fifteen healthy ...
Ryhner T, Müller N, Balmer V, Gerber V.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 ...
DeLuca L, Erb HN, Young JC, Perkins GA, Ainsworth DM.Chemokine expression in airway epithelium and bronchoalveolar lavage fluid (BALF) cells of horses with recurrent airway obstruction (RAO) is increased. Objective: For RAO-affected horses that are stabled and fed a pelleted ration, the addition of oral dexamethasone further improves pulmonary function and reduces inflammatory gene expression in pulmonary cells. Methods: Twelve RAO-affected horses. Methods: In a randomized cross-over experiment, the effect of feeding pellets in lieu of hay to stabled, RAO-affected horses was compared with the effect of feeding pellets and administering a 21-day ...
Riihimäki M, Raine A, Pourazar J, Sandström T, Art T, Lekeux P, Couëtil L, Pringle J.The aim of this study was to evaluate the contribution of bronchial epithelium to airway inflammation, with focus on mRNA and protein expression of cytokines of innate immunity IL-6, IL-10 and TNF-alpha, in horses with Recurrent Airway Obstruction (RAO) during exacerbation and in remission. Results: Despite marked clinical and physiologic alterations between exacerbation and after remission in the RAO horses no differences were detected in either cytokine mRNA or protein levels. Moreover, the expression of investigated cytokines in RAO horses on pasture did not differ from controls. In compari...
Theegarten D, Sachse K, Mentrup B, Fey K, Hotzel H, Anhenn O.Recurrent airway obstruction (RAO) in horses is a naturally occurring dust-induced disease mainly characterized by bronchiolitis which shows histological and pathophysiological similarities to human chronic obstructive pulmonary disease (COPD). In human COPD previous investigations indicated an association with Chlamydophila psittaci infection. The present study was designed (1) to clarify a possible role of this infectious agent in RAO and (2) to investigate the suitability of this equine disorder as a model for human COPD. Methods: Clinico-pathological parameters of a total of 45 horses (25 ...
Gehlen H, Bubeck K, Rohn K, Stadler P.The aim of this study was to investigate the potential haemodynamic effects of valvular insufficiency and recurrent airway obstruction (RAO) in horses with atrial fibrillation (AF). Therefore in ten healthy horses (group 1) and 40 horses with AF a clinical examination, a lung examination, echocardiography and right heart catheterization for measurement of intracardic and pulmonary pressures were performed. According to the clinical findings the horses with AF were subdivided into 4 groups (group 2: AF; group 3: AF/valvular insufficiency; group 4: AF/RAO; group 5: AF/valvular insufficiency/RAO)...
Riihimäki M, Raine A, Art T, Lekeux P, Couëtil L, Pringle J.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...
Dunkel B, Rickards KJ, Page CP, Cunningham FM.Platelet activation occurs in human obstructive airway diseases and in laboratory animal models. However, there is limited evidence that platelets may be involved in equine recurrent airway obstruction (RAO) and other inflammatory diseases. This study investigated whether platelet activation also occurred in RAO. Objective: Platelet function is altered in ponies with active RAO. This alteration can be detected ex vivo by measuring platelet adhesion. Methods: An in vitro platelet adhesion assay measuring acid phosphatase (AcP) activity colorimetrically was adapted for use with equine platelets ...
Ainsworth DM, Wagner B, Erb HN, Young JC, Retallick DE.To examine effects of in vitro exposure to solutions of hay dust, lipopolysaccharide (LPS), or beta-glucan on cytokine expression in pulmonary mononuclear cells isolated from healthy horses and horses with recurrent airway obstruction (RAO). Methods: 8 RAO-affected and 7 control horses (experiment 1) and 6 of the RAO-affected and 5 of the control horses (experiment 2). Methods: Bronchoalveolar lavage cells were isolated from horses that had been stabled and fed dusty hay for 14 days. Pulmonary mononuclear cells were incubated for 24 (experiment 1) or 6 (experiment 2) hours with PBS solution or...
Range F, Mundhenk L, Gruber AD.The equine putative chloride channel protein eCLCA1 is thought to be critically involved in the pathogenesis of recurrent airway obstruction (RAO) via modulation of the hydration of airway mucins. A recent study revealed a strong increase of eCLCA1 messenger ribonucleic acid (mRNA) in the lungs of horses with RAO. In this study, eCLCA1 protein and mRNA expression were quantified in airway goblet cells of 9 horses affected with RAO and 9 control horses by using immunohistochemistry and laser microdissection followed by real-time quantitative reverse transcription polymerase chain reaction, resp...
Cunningham FM, Dunkel B.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...
Miskovic M, Couëtil LL, Thompson CA.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...
Joubert P, Cordeau ME, Boyer A, Silversides DW, Lavoie JP.Heaves, also known as recurrent airway obstruction, is a common condition of horses characterised by pulmonary neutrophilia and reversible airway obstruction. This study evaluated the role of neutrophils in producing cytokines and chemokines that might be involved in the recruitment and activation of inflammatory cells in horses with heaves. Peripheral neutrophils were isolated from heaves-affected (n = 9) and control (n = 4) horses before and after 5 h of natural inhalation challenge. Expression of mRNA of two pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)...
Abraham G, Kottke C, Ungemach FR.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...
Scantlebury CE, Archer DC, Proudman CJ, Pinchbeck GL.Recurrent colic occurs frequently in the general horse population but little evidence exists about what factors place horses at greater risk of recurrent colic. Objective: To quantify time-varying and non time-varying risk factors for recurrent colic among horses attended by first-opinion veterinary surgeons in northwest England. Methods: Nested case-control study. Methods: A nested case-control study was conducted on data from a prospective longitudinal cohort study of 127 horses recruited subsequent to an episode of medical colic. Data were collected on management and recurrent colic episode...
Niedzwiedz A, Jaworski Z.Systemic oxidative stress in horses with recurrent airway obstruction (RAO) is poorly characterized. Objective: The goal of this study was to investigate whether equine RAO is associated with systemic disturbances in the oxidant-antioxidant equilibrium. Methods: Seven healthy horses and 7 horses with symptomatic RAO. Methods: A prospective study. Healthy and RAO-affected horses were exposed to a 48-hour challenge with moldy hay and straw to induce clinical exacerbation of RAO. Venous blood was collected and the activities of the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidas...
Cunningham FM, Dunkel B.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...
Deaton CM, Marlin DJ, Smith NC, Smith KC, Newton RJ, Gower SM, Cade SM, Roberts CA, Harris PA, Schroter RC, Kelly FJ.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 ...
Léguillette R, Lavoie JP.To evaluate whether bronchoalveolar lavage (BAL) alters respiratory mechanics of horses with recurrent airway obstruction (ie, heaves) over a 48-hour period. Methods: 6 horses affected with heaves. Methods: Horses were subjected to a complete BAL procedure, which included sedation with xylazine and butorphanol, intratracheal administration of lidocaine, and instillation and aspiration of two 250-mL boluses of saline (0.9% NaCl) solution through an endoscope (study 1). To evaluate the effects of saline solution, horses were subjected to the same procedure without saline solution instillation an...
Morán G, Burgos R, Araya O, Folch H.In horses, Recurrent Airway Obstruction (RAO) is an allergic disease that involves IgE mediated Type I Hypersensitivity responses. The development of this type of allergy involves a series of events that begins with reaginic antibodies, mainly IgE and some IgG subclasses. These reaginic antibodies bind with high affinity, via the Fc portion, to FcepsilonRI receptors on the membrane of mast cells and basophils. Once bound, environmental allergens cross-link the antibodies, which results in mast cell degranulation leading to the production of histamine and other chemical mediators that act toget...
Benamou AE, Art T, Marlin DJ, Roberts CA, Lekeux P.Recurrent airway obstruction (RAO) is an asthma-like condition of the horse that represents a major cause of morbidity and loss of performance. The exact pathogenesis of asthma in man is unclear but the role of endothelin (ET) is currently under investigation, thus sparking interest in the bronchoconstrictive and vasoconstrictive properties of endothelin in the equine-specific disease entity. In this study, we investigated the levels of ET-1 in systemic blood, as well as in bronchoalveolar lavage (BAL) from horses with RAO. We also studied how these values might correlate with those of lung fu...
Seahorn TL, Beadle RE, McGorum BC, Marley CL.To determine whether horses with summer pasture-associated obstructive pulmonary disease (SPAOPD) have increased concentrations of antigen-specific IgG and IgE in tracheal lavage fluid, compared with values in clinically normal horses. Methods: 8 horses (6 females, 2 geldings; 6 Quarter Horses, 2 Appaloosas), 14 to 23 years old and with previous diagnosis of SPAOPD, served as the principal group; 8 horses (2 females, 6 geldings; 1 Quarter Horse, 7 Thoroughbreds), 6 to 9 years old, with no evidence of respiratory tract disease, served as the control group. Methods: Data were collected twice dur...
Khol-Parisini A, van den Hoven R, Leinker S, Hulan HW, Zentek J.A crossover feeding trial was performed with 9 horses suffering from recurrent airway obstruction (RAO). The study aimed to determine whether ingestion of sunflower oil (SFO), rich in linoleic acid, or seal blubber oil (SBO), a source of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), changes the fatty acid (FA) ratios in plasma and leukocyte membrane phospholipids (PLs) or the leukocyte numbers or proportions of cell types in the airways. We also investigated diet-related changes in respiratory rate, maximum change in pleural pressure (deltaPpl(max)), dynamic compliance (C(dyn)...
Matera MG, Amorena M, Lucisano A.Equine obstructive pulmonary disease (COPD), or heaves or recurrent airway obstruction, is a common equine pulmonary disease similar to human asthma and/or CODP. Since bronchospasm and inflammation are the key features in heaves, the purpose of this paper is to review the contribution of neural mechanism that may be relevant to this disease. Equine airway receive cholinergic and adrenergic innervation, as well as observed in many species. It was suggested that the autonomic neural control in asthma might be defective with an imbalance between excitatory and inhibitory pathways, resulting in ex...
Wysocka B, Kluciński W.The aim of the present study was to use endoscopic evaluation to compare the grade of accumulation of discharge in the lower airways of horses with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD), and to estimate the usefulness of endoscopic evaluation in differential diagnosis of these diseases. Endoscopic evaluation consists of: the amount of discharge in the lower part of the trachea and tracheal bifurcation, and the assessment of tracheal septum thickness. This study was performed on 248 horses, 10 were healthy, 97 were diagnosed as RAO, and 141 were diagnosed as I...
Herholz C, Straub R, Braendlin C, Imhof A, Lüthi S, Busato A.Tidal breathing flow-volume loop (TBFVL) indices in healthy horses and in horses suffering from mild and moderate to severe recurrent airway obstruction (RAO) were measured. In addition, the ability of these indices to differentiate healthy controls from horses with mild RAO by separating the horses according to their usage was investigated. The horses were assigned to three sporting categories: 1 Leisure horses; 2 Horses competing at events with a duration of more than five minutes (eventing, coaching and endurance); and 3 Horses competing at events with a duration of less than five minutes (...
Venugopal C, Mariappan N, Holmes E, Kearney M, Beadle R.To determine and compare the reactive oxygen and nitrogen species (ROS and RNS) in pulmonary tissues of horses affected with recurrent airway obstruction (RAO) and clinically healthy horses, and to evaluate the effectiveness of potential therapeutic agents in reducing ROS and RNS in the tissues of these horses. Objective: We hypothesised that RAO-affected horses would have high levels of reactive species and that the test agents would reduce them. The objectives were as follows: 1) to determine the level of ROS and RNS in pulmonary tissues (bronchial and arterial rings) of RAO-affected and cli...
Widdicombe JH, Pecson IS.Horses commonly suffer from respiratory diseases associated with excess secretions in the airway lumen, some of which are presumably derived from airway mucous glands. However, these structures have been little investigated in the horse. Accordingly, we describe here the number, distribution and size of equine tracheal mucous glands, and compare the data with similar information for other mammalian species. Two types of gland acini were present. In the thick connective tissue, up to 400 microm beneath the epithelium, gland acini were grouped in thin sheets that, in cross-section, averaged 20 m...
Jefcoat AM, Hotchkiss JA, Gerber V, Harkema JR, Basbaum CB, Robinson NE.Horses with the episodic asthmalike condition of recurrent airway obstruction (RAO) have bouts of inflammation and bronchoconstriction associated with indoor housing. To assess the potential differences in airway secretions between RAO-affected and control horses, methods to quantify mucus secretions were developed and applied to bronchoalveolar lavage fluid. The relative difference in the amount of mucin glycoproteins between control and RAO-affected horses was assessed with a carbohydrate side chain-specific monoclonal antibody (4E4) in an enzyme-linked immunosorbent assay and by carbohydrat...
Lavoie JP, Thompson D, Hamilton E, Debrue M, David F, Hickey G.It has been suggested that many of the beneficial effects of corticosteroids are mediated through mitogen-activated protein kinase (MAPK) p38 inhibition. Objective: To investigate the efficacy of the MAPK p38 inhibitor compound MRL-EQ1 to either prevent (Phase 1) or treat (Phase 2) recurrent airway obstruction (RAO) in horses. Methods: MRL-EQ1 was administered i.v. at a dosage of 0.75-1.5 mg/kg bwt q. 12 h. In Phase 1, susceptible horses in clinical remission were divided into 2 groups (n = 5/group), based on historical values of respiratory mechanics. All horses were entered in the study in p...
Leclere M, Bédard C, Cortes-Dubly ML, Lavoie JP.As inflammation and coagulation are intertwined processes, the efficiency of blood coagulation of heaves-affected horses and controls were compared in an observational case-control study, using thrombelastography. In experiment 1 (Exacerbation, six heaves, five controls), horses were housed indoors and fed hay. Thrombelastography, functional fibrinogen, platelet count, hematology, and antithrombin were measured. In experiment 2 (Remission, eight heaves, 11 controls), horses were housed in a low-dust environment for at least a month when thrombelastography was performed. Heaves-affected horses ...
Ramery E, Closset R, Bureau F, Art T, Lekeux P.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...
Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P.Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-α in myeloid cells in ho...
Mazan MR, Deveney EF, DeWitt S, Bedenice D, Hoffman A.This study was conducted to determine whether horses with naturally occurring, severe chronic recurrent airway obstruction (RAO) 1). have a greater resting energy expenditure (REE) than control horses, 2). suffer body mass depletion, and 3). have significantly decreased REE after bronchodilation and, therefore, also 4). whether increased work of breathing contributes to the cachexia seen in some horses with RAO. Six RAO horses and six control horses underwent indirect calorimetric measures of REE and pulmonary function testing using the esophageal balloon-pneumotachograph method before and aft...
Wyse CA, Skeldon K, Hotchkiss JW, Gibson G, Yam PS, Christley RM, Preston T, Cumming DR, Padgett M, Cooper JC, Love S.The aim of this study was to assess the effects of changes to the stable environment on exhaled markers of respiratory inflammation in six horses with clinical histories of recurrent airway obstruction. The horses were maintained for two weeks under conventional stable management (straw bedding and hay) and for two weeks on a reduced-dust regimen (paper bedding and ensiled grass), in a crossover study design. Exhaled ethane and carbon monoxide (CO) and exhaled breath condensate hydrogen peroxide (H(2)O(2)) were measured every three days under each regimen. The presence of clinical signs of air...
Gray PR, Derksen FJ, Robinson NE, Carpenter-Deyo LJ, Johnson HG, Roth RA.Airway obstruction and hyperreactivity are characteristics of human asthma and of "heaves," a naturally occurring respiratory disorder of horses and ponies. To document the role of cyclooxygenase products of arachidonic acid metabolism in the pathogenesis of heaves, we measured plasma and bronchoalveolar lavage (BAL) fluid concentrations of metabolites of thromboxane (TX)A2 and prostaglandins (PG) I2 and D2 in five affected ponies and their age- and gender-matched controls prior to and during acute airway obstruction precipitated by housing the ponies in a barn and exposing them to hay dust. P...
Rush BR, Worster AA, Flaminio MJ, Matson CJ, Hakala JE.To determine alteration in adrenocortical function in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. Methods: 6 horses with inducible and reversible heaves. Methods: Episodes of heaves were induced by exposure to moldy hay and straw for 7 days (natural challenge). Horses then underwent treatment (aerosolized beclomethasone, parenterally administered dexamethasone, and aerosolized propellant) for 7 days. Horses remained in the mold-contaminated environment for 7 days after discontinuat...
Deaton CM, Marlin DJ, Deaton L, Smith NC, Harris PA, Schroter RC, Kelly FJ.Following a period of airway inflammation the clearance of inflammatory cells along the mucociliary escalator may impose a considerable oxidant load on the trachea. Objective: To determine the degree of oxidative stress in tracheal epithelial lining fluid (ELF) in comparison to that present in peripheral airways after an acute exposure to organic dust. Methods: Tracheal wash fluid and bronchoalveolar lavage fluid (BALF) were collected for cytology and antioxidant analyses from 6 recurrent airway obstruction (RAO)-affected horses and 6 healthy control horses before and after stabling on straw b...
Young SS, Tesarowski D, Viel L.The effect of measurement frequency on respiratory mechanics was investigated in six horses with reversible allergic airway disease. Total respiratory impedance was measured at 1.5, 2.0, 3.0, and 5.0 Hz by using the forced oscillation technique with the horses in remission, after acute antigenic challenge producing clinical heaves, and with heaves but after the administration of 2 mg fenoterol by inhalation. The slopes of the magnitude (magnitude of Zrs) and real part (R) of total respiratory impedance over the frequency range 1.5-3 Hz changed significantly after antigenic challenge and fenote...
Hare JE, Viel L, Conlon PD, Marshall JS.To determine the capacity of pulmonary mast cells (PMC) to degranulate in response to various potential allergens and other secretagogues in horses with recurrent airway obstruction (heaves) and clinically normal horses before and after exposure to moldy hay. Methods: 5 horses with heaves and 5 clinically normal horses. Methods: Heaves was characterized as an increased clinical respiratory score and maximum change in transpulmonary pressure of > 20 cm H2O after exposure. Bronchoalveolar lavage was performed during each period. Washed and resuspended cells were exposed for 20 minutes at 37 C wi...
Bertin FR, Ivester KM, Couëtil LL.Studies investigating the clinical efficacy of albuterol administered with the same propellant and commercially available delivery devices in horses with recurrent airway obstruction (RAO) are not currently available. Objective: To determine the efficacy of aerosolised albuterol administered to horses with RAO by means of 2 commercially available, hand-held delivery devices. Methods: Ten horses with RAO were kept in a dusty environment and fed mouldy hay to induce airway obstruction. Lung mechanics were measured before and after the procedure. ΔP(max) was measured 5 min after administration o...
