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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.
The role of oxidative stress in an equine model of human asthma.
Redox report : communications in free radical research    May 12, 2006   Volume 11, Issue 2 46-52 doi: 10.1179/135100006X101057
Deaton CM.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.
American journal of veterinary research    February 4, 2006   Volume 67, Issue 2 348-357 doi: 10.2460/ajvr.67.2.348
Polikepahad S, Paulsen DB, Moore RM, Costa LR, Venugopal CS.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 Veterinary record    December 6, 2005   Volume 157, Issue 23 733-736 doi: 10.1136/vr.157.23.733
Anour R, Leinker S, van den Hoven R.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.
Veterinary immunology and immunopathology    September 21, 2005   Volume 109, Issue 3-4 289-295 doi: 10.1016/j.vetimm.2005.08.019
Simonen-Jokinen T, Maisi P, Tervahartiala T, McGorum B, Pirie S, Sorsa T.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.
Respiratory research    September 15, 2005   Volume 6, Issue 1 104 doi: 10.1186/1465-9921-6-104
Matera MG, Calzetta L, Peli A, Scagliarini A, Matera C, Cazzola M.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.
Veterinary immunology and immunopathology    September 12, 2005   Volume 109, Issue 1-2 31-36 doi: 10.1016/j.vetimm.2005.06.017
Dewachi O, Joubert P, Hamid Q, Lavoie JP.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.
Veterinary journal (London, England : 1997)    August 29, 2005   Volume 173, Issue 1 144-150 doi: 10.1016/j.tvjl.2005.07.020
Pirrone F, Albertini M, Clement MG, Lafortuna CL.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.
Pulmonary pharmacology & therapeutics    August 3, 2005   Volume 19, Issue 3 218-229 doi: 10.1016/j.pupt.2005.05.007
Abraham G, Kottke C, Dhein S, Ungemach FR.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 journal of histochemistry and cytochemistry : official journal of the Histochemistry Society    May 6, 2005   Volume 53, Issue 8 1011-1021 doi: 10.1369/jhc.4A6599.2005
Anton F, Leverkoehne I, Mundhenk L, Thoreson WB, Gruber AD.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.
Veterinary immunology and immunopathology    March 31, 2005   Volume 105, Issue 1-2 25-31 doi: 10.1016/j.vetimm.2004.12.013
Debrue M, Hamilton E, Joubert P, Lajoie-Kadoch S, Lavoie JP.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.
Journal of applied physiology (Bethesda, Md. : 1985)    February 10, 2005   Volume 98, Issue 6 2132-2136 doi: 10.1152/japplphysiol.01218.2004
Davis MS, Malayer JR, Vandeventer L, Royer CM, McKenzie EC, Williamson KK.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.
Equine veterinary journal    October 6, 2004   Volume 36, Issue 6 489-494 doi: 10.2746/0425164044877323
Wilson DV, Berney CE, Peroni DL, Mullineaux DR, Robinson NE.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.
Veterinary immunology and immunopathology    September 8, 2004   Volume 101, Issue 3-4 133-141 doi: 10.1016/j.vetimm.2004.03.008
Desjardins I, Theoret C, Joubert P, Wagner B, Lavoie JP.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.
The Journal of allergy and clinical immunology    August 17, 2004   Volume 114, Issue 2 Suppl S2-S17 doi: 10.1016/j.jaci.2004.04.039
Hirst SJ, Martin JG, Bonacci JV, Chan V, Fixman ED, Hamid QA, Herszberg B, Lavoie JP, McVicker CG, Moir LM, Nguyen TT, Peng Q, Ramos-Barbón D....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.
The Journal of nutrition    July 31, 2004   Volume 134, Issue 8 Suppl 2133S-2140S doi: 10.1093/jn/134.8.2133S
Marlin DJ, Johnson L, Kingston DA, Smith NC, Deaton CM, Mann S, Heaton P, Van Vugt F, Saunders K, Kydd J, Harris PA.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.
Pulmonary pharmacology & therapeutics    May 5, 2004   Volume 17, Issue 3 163-172 doi: 10.1016/j.pupt.2004.02.001
Rickards KJ, Page CP, Cunningham FM.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.
Free radical research    April 24, 2004   Volume 38, Issue 2 201-208 doi: 10.1080/10715160310001638047
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 ...
[Mite allergy in the domestic horse: experience of an equine veterinarian specializing in the field of allergy].
European annals of allergy and clinical immunology    March 16, 2004   Volume 36, Issue 1 6-8 
Volland-Francqueville M, Sabbah A.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.
IL-4, IL-5 and IFN-gamma mRNA expression in pulmonary lymphocytes in equine heaves.
Veterinary immunology and immunopathology    January 1, 2004   Volume 97, Issue 1-2 87-96 doi: 10.1016/j.vetimm.2003.08.013
Cordeau ME, Joubert P, Dewachi O, Hamid Q, Lavoie JP.Heaves is a common condition of horses of cold climate that is characterized by small airway inflammation and obstruction following exposure of susceptible horses to moldy hay and straw. It has been shown that helper T lymphocytes (Th) orchestrate the inflammatory response in asthma and in various animal models of allergic lung diseases by the release of Th2-type cytokines. Results of previous studies indicate that a predominant expression of Th2-type response by airway cells may also be present in heaves. To evaluate the temporal mRNA expression of Th1 (IFN-gamma) and Th2 (IL-4, IL-5) type cy...
Use of the impulse oscillometry system for testing pulmonary function during methacholine bronchoprovocation in horses.
American journal of veterinary research    November 19, 2003   Volume 64, Issue 11 1414-1420 doi: 10.2460/ajvr.2003.64.1414
van Erck E, Votion DM, Kirschvink N, Art T, Lekeux P.To compare sensitivity of the impulse oscillometry system (IOS) with that of the conventional reference technique (CRT; ie, esophageal balloon method) for pulmonary function testing in horses. Methods: 10 horses (4 healthy; 6 with recurrent airway obstruction [heaves] in remission). Methods: Healthy horses (group-A horses) and heaves-affected horses (group-B horses) were housed in a controlled environment. At each step of a methacholine bronchoprovocation test, threshold concentration (TC(2SD); results in a 2-fold increase in SD of a value) and sensitivity index (SI) were determined for respir...
Pharmacological and biochemical characterization of the beta-adrenergic signal transduction pathway in different segments of the respiratory tract.
Biochemical pharmacology    September 10, 2003   Volume 66, Issue 6 1067-1081 doi: 10.1016/s0006-2952(03)00460-x
Abraham G, Kottke C, Dhein S, Ungemach FR.Although in the respiratory system there is great therapeutic interest in manipulating and understanding the beta-adrenoceptor-G-protein-adenylate cyclase (AC) signal transduction pathway, little is known on segmental differences among lung, bronchus, and trachea with regard to the receptor concentration and interaction to G-proteins and coupling to AC. In this study, patterns of distribution and absolute quantities of beta-adrenoceptor subtypes beta(1) and beta(2) were determined in membranes of equine lung parenchyma, bronchial and tracheal epithelium with the underlying smooth muscle by sat...
Efficacy of montelukast in the treatment of chronic obstructive pulmonary disease in five horses.
The Veterinary record    July 17, 2003   Volume 152, Issue 26 804-806 doi: 10.1136/vr.152.26.804
Kolm G, Zappe H, Schmid R, Riedelberger K, Van den Hoven R.Five horses with moderate to severe chronic obstructive pulmonary disease (COPD) were treated with 0.11 (0.01) mg/kg bodyweight of montelukast, a cysteinyl leukotriene receptor antagonist, once a day for 26 days. The horses were evaluated clinically and endoscopically and subjected to arterial blood gas analysis and lung function tests before and after the period of treatment, and the plasma concentrations of montelukast were determined by high-performance liquid chromatography with fluorescence detection. The treatment did not result in statistically significant differences in the total score...
Excessive airway mucus in horses with pulmonary disease: is it caused by mucus overproduction, decreased clearance or both?
Equine veterinary journal    May 21, 2003   Volume 35, Issue 3 222-223 doi: 10.2746/042516403776148192
Dixon PM, Pirie RS.No abstract available
Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma).
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology    May 20, 2003   Volume 33, Issue 5 676-683 doi: 10.1046/j.1365-2222.2003.01640.x
Pirie RS, Collie DD, Dixon PM, McGorum BC.Equine heaves is a naturally occurring organic dust-induced asthma characterized by airway neutrophilia, mucus hypersecretion and obstructive lung dysfunction. However, the relative role of different dust components in disease severity remains unclear. Objective: This study investigated the relative contribution of inhaled endotoxin and organic dust particulates (mainly mould spores) in inducing heaves in heaves-susceptible horses. Methods: Control and heaves-susceptible horses received inhalation challenges with hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. He...
Innervation of equine airways.
Pulmonary pharmacology & therapeutics    December 21, 2002   Volume 15, Issue 6 503-511 doi: 10.1006/pupt.2002.0390
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...
Detection of inhaled salbutamol in equine urine by ELISA and GC/MS2.
Biomedical chromatography : BMC    December 11, 2002   Volume 16, Issue 8 513-516 doi: 10.1002/bmc.194
Eenoo PV, Delbeke FT.Salbutamol is a beta-adrenergic agonist that is used in the treatment of asthma in humans and chronic obstructive pulmonary disease in horses. Because of its stimulating and growth promoting properties, it is prohibited by horse racing authorities. Recently a number of adapters (eg Equinehaler) have been designed, allowing the use of metered dose inhalers (MDI) approved for human use. However, information on detection times of salbutamol after administration of salbutamol in therapeutic doses by inhalation is lacking. In this study, 2 mg salbutamol (Ventolin) was administered to four standardb...
Effect of chronic airway inflammation and exercise on pulmonary and systemic antioxidant status of healthy and heaves-affected horses.
Equine veterinary journal    October 3, 2002   Volume 34, Issue 6 563-571 doi: 10.2746/042516402776180223
Kirschvink N, Smith N, Fiévez L, Bougnet V, Art T, Degand G, Marlin D, Roberts C, Génicot B, Lindsey P, Lekeux P.In heaves-affected horses the relation between oxidant status, airway inflammation (AI) and pulmonary function (PF) is unknown. The oxidant status of blood and pulmonary epithelial lining fluid (PELF) of healthy (H, n = 6) and heaves-affected horses in clinical remission (REM, n = 6) and in crisis (CR, n = 7) was assessed at rest, during and after standardised exercise test by measurement of reduced and oxidised glutathione, glutathione redox ratio [GRR%]; uric acid and 8-epi-PGF2alpha. Oxidant status was related to PF parameters (mechanics of breathing and arterial blood gas tension) and Al p...
Sensitization to horse hair, symptoms and lung function in grooms.
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology    August 23, 2002   Volume 32, Issue 8 1170-1173 doi: 10.1046/j.1365-2745.2002.01439.x
Tutluoglu B, Atiş S, Anakkaya AN, Altug E, Tosun GA, Yaman M.This study aimed to investigate the rate of occupational sensitization to horse hair in grooms and whether occupational exposure to horse hair increases respiratory and allergic symptoms and affects lung function in grooms or not. Methods: This is a cross-sectional study. Two hundred grooms were randomly selected among 1000 grooms working in Veliefendi Hippodrome of Istanbul. One hundred and twenty-five subjects agreed to enter the study. Ninety-two workers who worked in the different parts of this hippodrome enrolled as the control group. A detailed questionnaire including respiratory and all...
Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 3: Effect of fractionation of HDS.
Equine veterinary journal    July 16, 2002   Volume 34, Issue 4 343-347 doi: 10.2746/042516402776249236
Pirie RS, Dixon PM, McGorum BC.To investigate the relative importance of inhaled particulates and soluble components in the response to inhaled hay dust suspension (HDS), heaves (previously termed chronic obstructive pulmonary disease; n = 7) and control (n = 6) horses were given inhalation challenges with whole and fractionated HDS. Fractionation was achieved by centrifugation to yield supernatant (SUP) and particulate debris. The particulates were then washed repeatedly in saline to produce a washed particulate (WP) fraction which comprised mainly fungal spores, and a wash fraction (WF) which comprised saline and soluble ...
Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 2: Effects of inhaled HDS on control and heaves horses.
Equine veterinary journal    July 16, 2002   Volume 34, Issue 4 337-342 doi: 10.2746/042516402776249074
Pirie RS, Collie DD, Dixon PM, McGorum BC.To evaluate inhaled hay dust suspensions (HDS) as a tool for the diagnosis and investigation of heaves, the pulmonary inflammatory and functional consequences of inhalation challenge with 3 different HDS were determined in 6 control and 7 asymptomatic heaves horses. Heaves horses given HDS challenge developed the characteristic features of heaves, including airway neutrophilia, obstructive airway dysfunction and mucus hypersecretion. While HDS challenge induced a mild airway neutrophilia in controls, the no-response threshold for controls was greater than that of heaves horses, and there was n...