The bronchi are part of the lower respiratory tract in horses, serving as air passages that conduct inhaled air from the trachea into the lungs. These tubular structures branch into smaller bronchioles, leading to the alveoli where gas exchange occurs. The health and function of the bronchi are critical for maintaining respiratory efficiency and overall equine health. Conditions affecting the bronchi, such as bronchitis or bronchoconstriction, can impact a horse's respiratory performance and are often a focus in equine veterinary medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the anatomy, physiology, and pathophysiology of the bronchi in horses, as well as diagnostic and therapeutic approaches for bronchial conditions.
Vinardell T, David F, Galezowski AM, Ali M, Qasim M, Massie SL, McCrae P, Filho S, Leguillette R.Swimming is used for rehabilitation of musculoskeletal injuries and for conditioning to improve equine fitness. However, there are anecdotal reports that suggest that tethered swimming can induce epistaxis, likely secondary to exercise-induced pulmonary hemorrhage (EIPH). The objective of this observational, prospective study was to investigate if EIPH occurs during intensive free-swimming training sessions (5 × 70m) using 15 endurance horses. On tracheo-bronchoscopic evaluations following swimming, low grade mucus scores were observed, but no tracheal blood was observed. Bronchoalveolar la...
Airway inflammation and airway hyperresponsiveness (AHR) are pivotal characteristics of equine asthma. Lipopolysaccharide (LPS) may have a central role in modulating airway inflammation and dysfunction. Therefore, the aim of this study was to match the inflammatory and contractile profile in LPS-challenged equine isolated bronchi to identify molecular targets potentially suitable to counteract AHR in asthmatic horses. Equine isolated bronchi were incubated overnight with LPS (0.1-100 ng/ml). The contractile response to electrical field stimulation (EFS) and the levels of cytokines, chemokines...
Adamič N, Prpar Mihevc S, Blagus R, Kramarič P, Krapež U, Majdič G, Viel L, Hoffman AM, Bienzle D, Vengust M.Severe equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA. This was a randomized controlled trial. Twenty adult horses diagnosed with SEA were random...
Mainguy-Seers S, Boivin R, Pourali Dogaheh S, Beaudry F, Hélie P, Bonilla AG, Martin JG, Lavoie JP.Steroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease. Macrolide add-on therapy can improve the quality of life and the exacerbation rate in refractory cases, possibly with greater effectiveness in neutrophilic phenotypes. The mechanisms leading to these beneficial effects are incompletely understood and whether macrolides potentiate the modulation of bronchial remodeling induced by inhaled corticosteroids (ICS) is unknown. The objective of this study was to determine if adding azithromycin to ICS leads to further improvement o...
Schellenberg LM, Regenthal R, Abraham G.This research paper investigates the influence of the Rho kinase (ROCK) inhibitor Y-27632 on β2-adrenoceptor density and the generation of a cellular messenger called cAMP in horse bronchial cells. The […]
Mönki J, Saastamoinen M, Karikoski N, Norring M, Rajamäki M, Mykkänen A.The effects of bedding material on air quality are important amongst horses worldwide. Respiratory diseases, especially equine asthma, are highly prevalent with air hygiene playing a major role on the pathophysiology of these diseases. The objective of our study was to investigate the effects of four bedding materials on the respiratory signs, tracheal mucus score, and tracheal wash (TW) and bronchoalveolar lavage fluid (BALF) cytology in healthy adult horses. The study design was a prospective controlled cross-over study, and the subjects were healthy adult riding school horses ( = 32) from a...
Lee GKC, Beeler-Marfisi J, Viel L, Piché É, Kang H, Sears W, Bienzle D.Horses with severe equine asthma (SEA), also known as heaves and recurrent airway obstruction, have persistent neutrophilic inflammation of the lower airways. Cytologic evaluation of bronchoalveolar lavage (BAL) fluid is commonly used to confirm the clinical diagnosis of SEA. However, the utility of microscopic assessment of bronchial brushings, endobronchial biopsies, and immunohistochemical detection of disease-associated biomarkers for the diagnosis of SEA remain poorly characterized. Salivary scavenger and agglutinin (SALSA) has anti-inflammatory properties and downregulated gene expressio...
Bessonnat A, Hélie P, Grimes C, Lavoie JP.There is a remodeling of the central airways in horses with severe asthma but whether a similar process occurs in horses with the mild or moderate asthma (MMA) is unknown. Objective: To evaluate lesions affecting the central airways of horses with MMA. Methods: Twelve horses with MMA and 8 control horses. Methods: Case-control retrospective study of horses classified as MMA affected or controls based on history and bronchoalveolar lavage fluid cytology. Endobronchial biopsies were analyzed using histomorphometry and a semiquantitative histologic scoring system. Results: Histomorphometry identi...
Frontiers in allergyNovember 26, 2021
Volume 2 762026 doi: 10.3389/falgy.2021.762026
Ben Hamouda S, Miglino MA, de Sá Schiavo Matias G, Beauchamp G, Lavoie JP.Asthma is associated with increased deposition and altered phenotype of airway smooth muscle (ASM) cells. However, little is known about the processes responsible for these changes. It has been suggested that alterations of the extracellular matrix (ECM) contribute to the remodeling of ASM cells in asthma. Three-dimensional matrices allow the study of complex cellular responses to different stimuli in a close-to-natural environment. Thus, we investigated the ultrastructural and genic variations of ASM cells cultured on acellular asthmatic and control bronchial matrices. We studied horses, as ...
Dupuis-Dowd F, Lavoie JP.Airway smooth muscle remodelling in severe equine asthma includes both thickening of airway smooth muscle, resulting from hyperplasia and hypertrophy, and changes in contractility. However, airway smooth muscle changes have not been studied in milder forms of the disease. Objective: To investigate bronchial smooth muscle remodelling in horses with mild and moderate asthma (MEA). Methods: Retrospective case-control study. Methods: The endobronchial biopsies from 18 horses with MEA referred to the Equine Hospital of the Université de Montréal and from seven healthy age-matched control horses w...
Barton AK, Gehlen H.The term remodeling describes the process resulting in a tissue that is structurally and architecturally altered compared to its healthy counterpart. At least in severe equine asthma, this occurs mainly, but not exclusively, as a consequence of neutrophilic airway inflammation and is characterized by hypertrophy of the smooth muscle layers in airway and arterial walls as well as fibrosis of the bronchial walls and pulmonary interstitial tissue. To date, much less is known for mild to moderate equine asthma. For a long time it was assumed that these processes are irreversible, and at least for ...
Schellenberg LM, Regenthal R, Abraham G.The present study addresses the effect of the Rho-kinase (ROCK) inhibitor Y-27632 on the β-adrenoceptor density and β-agonist-stimulated intracellular second messenger cAMP formation in primary equine bronchial epithelial cells (EBEC). Y-27632 significantly decreased the β-adrenoceptor number (B) without markedly affecting the receptor affinity (dissociation constant, K) to the radioligand [I]-iodocyanopindolol (ICYP). In contrast, Y-27632 augmented the β-agonist-stimulated intracellular cAMP production. Herein, Y-27632 markedly increased the maximal cAMP responses (E) (isoproterenol >...
Sano Y, Kuwajima H, Kanai H, Baba C, Azami K, Matsuda K.A 24-year-old, Thoroughbred gelding presented with difficulty breathing for a few days and intermittent nose bleeding before dying. At necropsy, the bronchoesophageal artery and the bronchial artery that flowed into the left anterior lobe were tortuous and dilated, and it was found that dilated tortuous branches of the bronchial artery ran over the dorsal and ventral surfaces of the left anterior lobe. Histopathologically, an anastomosis between a muscular artery and an elastic artery were demonstrated, which were identified as bronchial and pulmonary arteries, respectively. Based on the gross...
Mainguy-Seers S, Lavoie JP.Despite substantial research efforts to improve the treatment and outcome of horses with asthma, glucocorticoids (GC) remain the cornerstone of drug treatment of this prevalent disease. The high efficacy of GC to relieve airway obstruction explains their extensive use despite potential deleterious effects. However, much is yet to be uncovered concerning GC use in horses with asthma, including the comparative efficacy of the different drugs, the determination of minimal effective doses and the mechanisms underlying their variable modulation of airway inflammation. The objectives of this structu...
Millares-Ramirez EM, Lavoie JP.Severe asthma in horses is characterized by structural changes that thicken the lower airway wall, a change that is only partially reversible by current treatments. Increased vascularization contributes to the thickening of the bronchial wall in humans with asthma and is considered a potential new therapeutic target. Objective: To determine the presence of angiogenesis in the bronchi of severely asthmatic horses, and if present, to evaluate its reversibility by treatment with corticosteroids. Methods: Study 1: Bronchial samples from asthmatic horses in exacerbation (7), in remission (7), and a...
Morini M, Peli A, Rinnovati R, Magazzù G, Romagnoli N, Spadari A, Pietra M.Severe equine asthma (EA) syndrome is a chronic obstructive disease characterized by exaggerated contraction, inflammation, and structural alteration of the airways in adult horses, when exposed to airborne molds and particulate material. However, little is known about the relationship between the degree and type of inflammation on one hand, and the severity of the disease and the response to treatment on the other. Furthermore, to date, very few studies evaluate the diagnostic value of histology and immunohistochemical features of endoscopic biopsies on subjects with severe equine asthma. To ...
Dixon CE, Bedenice D, Mazan MR.Airway hyperresponsiveness (AHR) is linked to airway inflammation and is considered a key manifestation of mild/moderate equine asthma (EA). The study purpose was to determine whether two modalities of non-invasive lung function testing (FOM-forced oscillatory mechanics vs. FP-flowmetric plethysmography) establish the same clinical diagnosis of AHR in horses, using histamine bronchoprovocation. Nineteen horses (3-25 years, 335-650 kg) with clinical signs suggestive of mild/moderate equine asthma were enrolled. FOM and FP testing was performed in each horse on two consecutive days, using a rand...
Legere RM, Cohen ND, Poveda C, Bray JM, Barhoumi R, Szule JA, de la Concha-Bermejillo A, Bordin AI, Pollet J.Vaccines and therapeutics using in vitro transcribed mRNA hold enormous potential for human and veterinary medicine. Transfection agents are widely considered to be necessary to protect mRNA and enhance transfection, but they add expense and raise concerns regarding quality control and safety. We found that such complex mRNA delivery systems can be avoided when transfecting epithelial cells by aerosolizing the mRNA into micron-sized droplets. In an equine in vivo model, we demonstrated that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (...
Ben Hamouda S, Vargas A, Boivin R, Miglino MA, da Palma RK, Lavoie JP.Severe asthma is associated with an increased airway smooth muscle (ASM) mass and altered composition of the extracellular matrix (ECM). Studies have indicated that ECM-ASM cell interactions contribute to this remodeling and its limited reversibility with current therapy. Three-dimensional matrices allow the study of complex cellular responses to different stimuli in an almost natural environment. Our goal was to obtain acellular bronchial matrices and then develop a recellularization protocol with ASM cells. We studied equine bronchi as horses spontaneously develop a human asthma-like disease...
Schellenberg LM, Bonicelli J, Hochheim I, Regenthal R, Abraham G.The β-adrenergic receptor (β-AR) plays an important role in regulating a variety of cell and organ functions in different animal species and is an important target in asthma pathogenesis and therapy. The β-AR expression and function in equine bronchial epithelial cells (EBEC) were not known but innervation and significant decrease in receptor level were reported in the equine bronchial tissues from asthmatic horses. I-iodocyanopindolol (ICYP) binding studies were undertaken in primary freshly isolated and cultured EBEC to identify the presence of the β-ARs. The receptor distribution was as...
Abs V, Bonicelli J, Kacza J, Zizzadoro C, Abraham G.Interaction between epithelial cells and fibroblasts play a key role in wound repair and remodelling in the asthmatic airway epithelium. We present the establishment of a co-culture model using primary equine bronchial epithelial cells (EBECs) and equine bronchial fibroblasts (EBFs). EBFs at passage between 4 and 8 were seeded on the bottom of 24-well plates and treated with mitomycin C at 80% confluency. Then, freshly isolated (P0) or passaged (P1) EBECs were seeded on the upper surface of membrane inserts that had been placed inside the EBF-containing well plates and grown first under liquid...
Bullone M, Lavoie JP.Human asthma is a complex and heterogeneous disorder characterized by chronic inflammation, bronchospasm and airway remodeling. The latter is a major determinant of the structure-function relationship of the respiratory system and likely contributes to the progressive and accelerated decline in lung function observed in patients over time. Corticosteroids are the cornerstone of asthma treatment. While their action on inflammation and lung function is well characterized, their effect on remodeling remains largely unknown. An important hindrance to the study of airway remodeling as a major focu...
Pozzoli C, Bertini S, Poli E, Placenza G, Menozzi A.β-adrenoceptor agonists are considered the most effective drugs to counteract bronchoconstriction in horses with asthma, but only clenbuterol is commonly employed in clinical practice. We evaluated the effects of different selective β agonists: clenbuterol, ritodrine, salbutamol, and fenoterol on the contractions of isolated bronchial muscle of horses induced by electrical field stimulation (EFS), carbachol, histamine, and KCl. All β agonists reduced the amplitude of contraction induced by the different stimuli but with variable efficacy and potency. Fenoterol and salbutamol were more effec...
Pre-clinical studies on human isolated bronchi have relevant translational value in human in vivo, conversely no investigation has been performed to assess whether data resulting from equine isolated airways can have any translational application in asthmatic horses. Thus, a meta-regression analysis via random-effect method was carried out to correlate the pharmacological characteristics of bronchodilators resulting from experiments performed in equine isolated bronchi with their impact on the lung function outcomes in asthmatic horses. Data on the potency of different bronchodilators were ext...
Varegg MS, Kløverød KM, Austnes MK, Siwinska N, Słowikowska M, Zak A, Madej JA, Kandefer-Gola M, Ciaputa R, Nowak M, Niedzwiedz A.Pulmonary hemorrhage is a rare cause of death in horses. Hemorrhage within the respiratory tract has many causes, including mycosis of the guttural pouch, invasive procedures causing serious trauma to nasal conchae, or lung biopsy. We report on a rare case of a fatal pulmonary hemorrhage in a horse after a severe cough during bronchoalveolar lavage. To the best of our knowledge, this is the first report of spontaneous hemorrhage in a horse during bronchoalveolar lavage. Methods: A 21-year-old mare which belonged to the didactic herd of The Faculty of Veterinary Medicine underwent BAL procedure...
Minato E, Aoshima K, Kobayashi A, Ohnishi N, Sasaki N, Kimura T.Equine herpesvirus 1 (EHV-1) uses equine major histocompatibility complex class I (MHC class I) as an entry receptor. Exogenous expression of equine MHC class I genes in murine cell lines confers susceptibility to EHV-1 infection. To examine the in vivo role of equine MHC class I as an entry receptor for EHV-1, we generated transgenic (Tg) mice expressing equine MHC class I under the control of the CAG promoter. Equine MHC class I protein was expressed in the liver, spleen, lung, and brain of Tg mice, which was confirmed by Western blot. However, equine MHC class I antigen was only detected in...
Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D.Severe equine asthma is a chronic inflammatory condition of the lower airways similar to adult-onset asthma in humans. Exacerbations are characterized by bronchial and bronchiolar neutrophilic inflammation, mucus hypersecretion and airway constriction. In this study we analyzed the gene expression response of the bronchial epithelium within groups of asthmatic and non-asthmatic animals following exposure to a dusty hay challenge. After challenge we identified 2341 and 120 differentially expressed genes in asthmatic and non-asthmatic horses, respectively. Gene set enrichment analysis of changes...
Issouf M, Vargas A, Boivin R, Lavoie JP.Smooth muscle has a central role in bronchospasm-induced airway obstruction in asthma. Alternative mRNA splicing of the smooth muscle myosin heavy chain (myh11) gene produces four different isoforms, one of which (SMB) is characterized by the inclusion of the exon5b, which doubles the smooth muscle cells contraction velocity. Deciphering the regulation of the expression levels of the SMB isoform would represent a major step for the understanding of the triggers and pathways leading to airway smooth muscle contraction in asthma. Our objective was therefore, to study the splicing regulation mech...
Ijpma G, Liang CQ, Kachmar L, Panariti A, Benedetti A, Lavoie JP, Lauzon AM.Isolated human airway smooth muscle (ASM) tissue contractility studies are essential for understanding the role of ASM in respiratory disease, but limited availability and cost render storage options necessary for optimal use. However, to our knowledge, no comprehensive study of cryopreservation protocols for isolated ASM has been performed to date. We tested several cryostorage protocols on equine trachealis ASM using different cryostorage media [1.8 M dimethyl sulfoxide and fetal bovine serum (FBS) or Krebs-Henseleit (KH)] and different degrees of dissection (with or without epithelium and c...
Leclere M, Lavoie-Lamoureux A, Lavoie JP.Animal models have been developed to investigate specific components of asthmatic airway inflammation, hyper-responsiveness or remodelling. However, all of these aspects are rarely observed in the same animal. Heaves is a naturally occurring disease of horses that combines these features. It is characterized by stable dust-induced inflammation, bronchospasm and remodelling. The evaluation of horses during well-controlled natural antigen exposure and avoidance in experimental settings allows the study of disease mechanisms in the asymptomatic and symptomatic stages, an approach rarely feasible ...
Leclere M, Lavoie-Lamoureux A, Joubert P, Relave F, Setlakwe EL, Beauchamp G, Couture C, Martin JG, Lavoie JP.Recent studies suggest that airway smooth muscle remodeling is an early event in the course of asthma. Little is known of the effects of long-term antigen avoidance and inhaled corticosteroids on chronically established airway remodeling. We sought to measure the effects of inhaled corticosteroids and antigen avoidance on airway remodeling in the peripheral airways of horses with heaves, a naturally occurring asthma-like disease. Heaves-affected adult horses with ongoing airway inflammation and bronchoconstriction were treated with fluticasone propionate (with and without concurrent antigen av...
Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA.Heaves in horses shares many similarities with human asthma, including lower airway inflammation, reversible airway obstruction, and bronchial hyperresponsiveness. Extrinsic asthma is an allergic response to environmental allergens and a similar immunologic mechanism may be implicated in heaves. It is now recognized that a Th2 subset of CD4+ lymphocytes is associated with allergic diseases such as atopic asthma. The purpose of this study was to determine whether airway inflammation in heaves is associated with a pattern of expression of cytokine suggestive of a Th2 type response. The expressio...
Leclere M, Lavoie-Lamoureux A, Gélinas-Lymburner E, David F, Martin JG, Lavoie JP.Recent studies suggest that airway smooth muscle remodeling is an early event in asthma, but whether it remains a dynamic process late in the course of the disease is unknown. Moreover, little is known about the effects of an antigenic exposure on chronically established smooth muscle remodeling. We measured the effects of antigenic exposure on airway smooth muscle in the central and peripheral airways of horses with heaves, a naturally occurring airway disease that shares similarities with chronic asthma. Heaves-affected horses (n = 6) and age-matched control horses (n = 5) were kept on pastu...
Gerber V, Lindberg A, Berney C, Robinson NE.Mucus accumulation and neutrophilic inflammation in the airways are hallmarks of heaves. Endoscopically visible mucus accumulations, however, have not been studied during exposure to dusty hay and allergens (ie, environmental challenge). We hypothesized that (1) heaves-affected horses have increased mucus accumulation compared with controls, (2) mucus accumulations increase in heaves-affected horses during environmental challenge, and (3) environmental challenge also induces neutrophilic inflammation and mucus accumulation in control horses. Mucus accumulation was graded endoscopically (mucus ...
Bullone M, Vargas A, Elce Y, Martin JG, Lavoie JP.Asthmatic airways are inflamed and undergo remodelling. Inhaled corticosteroids and long-acting β2-agonist combinations are more effective than inhaled corticosteroid monotherapy in controlling disease exacerbations, but their effect on airway remodelling and inflammation remains ill-defined. This study evaluates the contribution of inhaled fluticasone and salmeterol, alone or combined, to the reversal of bronchial remodelling and inflammation. Severely asthmatic horses (6 horses/group) were treated with fluticasone, salmeterol, fluticasone/salmeterol, or with antigen avoidance for 12 weeks. ...
Robinson NE, Derksen FJ, Olszewski MA, Buechner-Maxwell VA.Present evidence suggests that chronic obstructive pulmonary disease (COPD) of horses is a delayed hypersensitivity response to inhaled antigens, particularly the thermophilic moulds and actinomycetes that grow in damp hay. Within several hours of exposing COPD-susceptible horses to such hay, neutrophils invade the lung and accumulate in the lumens of airways, particularly bronchioles. The inflammatory response is accompanied by increased levels of histamine in bronchoalveolar lavage fluid, increased plasma levels of the inflammatory mediators thromboxane and 15-hydroxyeicosatetraenoic acid (1...
Bureau F, Delhalle S, Bonizzi G, Fiévez L, Dogné S, Kirschvink N, Vanderplasschen A, Merville MP, Bours V, Lekeux P.In most cells trans-activating NF-kappaB induces many inflammatory proteins as well as its own inhibitor, IkappaB-alpha, thus assuring a transient response upon stimulation. However, NF-kappaB-dependent inflammatory gene expression is persistent in asthmatic bronchi, even after allergen eviction. In the present report we used bronchial brushing samples (BBSs) from heaves-affected horses (a spontaneous model of asthma) to elucidate the mechanisms by which NF-kappaB activity is maintained in asthmatic airways. NF-kappaB activity was high in granulocytic and nongranulocytic BBS cells. However, NF...
Côté O, Clark ME, Viel L, Labbé G, Seah SY, Khan MA, Douda DN, Palaniyar N, Bienzle D.Secretoglobin family 1A member 1 (SCGB 1A1) is a small protein mainly secreted by mucosal epithelial cells of the lungs and uterus. SCGB 1A1, also known as club (Clara) cell secretory protein, represents a major constituent of airway surface fluid. The protein has anti-inflammatory properties, and its concentration is reduced in equine recurrent airway obstruction (RAO) and human asthma. RAO is characterized by reversible airway obstruction, bronchoconstriction and neutrophilic inflammation. Direct effects of SCGB 1A1 on neutrophil functions are unknown. We have recently identified that the SC...
Bureau F, Bonizzi G, Kirschvink N, Delhalle S, Desmecht D, Merville MP, Bours V, Lekeux P.Asthma is a chronic inflammatory disease of the airways, in which many inflammatory genes are overexpressed. Transcription factor, nuclear factor-kappaB (NF-kappaB), which is thought to control the transcriptional initiation of inflammatory genes, has been poorly investigated in asthma. In the present report, bronchial cells (BCs), recovered by bronchial brushing in healthy and heaves-affected horses (i.e., an animal model of asthma), were assessed for NF-kappaB activity. Small amounts of active NF-kappaB were present in BCs of healthy horses, whereas high levels of NF-kappaB activity was foun...
Setlakwe EL, Lemos KR, Lavoie-Lamoureux A, Duguay JD, Lavoie JP.The consequences on lung function and inflammation of alterations in the extracellular matrix affecting the peripheral airway wall in asthma are largely unknown. We hypothesized that remodeling of collagen and elastic fibers in the peripheral airway wall leads to airway obstruction and contributes to neutrophilic airway inflammation. Animals used were six heaves-affected horses and five controls. Large peripheral lung biopsies were obtained from horses with heaves in clinical remission (Baseline) and during disease exacerbation and from age-matched controls. The area of collagen and elastic fi...
Marti E, Gerber H, Essich G, Oulehla J, Lazary S.The genetic influence on chronic hypersensitivity bronchitis (CB) was investigated in families at two studs and among half-siblings of three affected and three non-affected sires at several farms. The family members at the two studs were born and raised under the same conditions, whereas the half-siblings were kept individually under very different conditions and were exposed to various environmental factors. The diagnosis was based on long-term observations and multiple clinical examinations at each of the two studs. In the half-sibling group, the diagnosis was based on the individual history...
Elfman L, Riihimäki M, Pringle J, Wålinder R.Many people spend considerable amount of time each day in equine stable environments either as employees in the care and training of horses or in leisure activity. However, there are few studies available on how the stable environment affects human airways. This study examined in one horse stable qualitative differences in indoor air during winter and late summer conditions and assessed whether air quality was associated with clinically detectable respiratory signs or alterations to selected biomarkers of inflammation and lung function in stable personnel. Methods: The horse stable environment...
Ainsworth DM, Wagner B, Franchini M, Grünig G, Erb HN, Tan JY.To evaluate time-dependent alterations in gene expression of chemokines in bronchial epithelium of recurrent airway obstruction (RAO)-affected horses and whether alterations resulted from increases in gene expression of interleukin (IL)-17 in cells isolated from bronchoalveolar lavage fluid (BALF). Methods: 8 RAO-susceptible horses and 9 control horses. Methods: In 2 experiments, both groups of horses were evaluated after being maintained on pasture and after being stabled and fed dusty hay for 1, 14, 35, and 49 days (experiment 1) or 14 and 28 days (experiment 2). In experiment 1, gene expres...
Padoan E, Ferraresso S, Pegolo S, Castagnaro M, Barnini C, Bargelloni L.The goal of the present study was to investigate mRNA expression levels of several cytokines and inflammatory mediators in broncho-alveolar lavage (BAL) fluid and respiratory epithelium in recurrent airway obstruction (RAO)-affected horses. RAO, also called heaves, is a common, performance-limiting, equine respiratory disease with clinical signs and pathophysiological similarities to human asthma, and characterized by bronchospasm, neutrophilic infiltration and increased mucus in the airways. Six RAO-affected horses were examined twice within 15 days and seven clinically healthy horses were ex...
Koblinger K, Nicol J, McDonald K, Wasko A, Logie N, Weiss M, Léguillette R.Comprehensive endoscopic scoring of the upper and lower airways for inflammation has not been critically assessed among a large population of horses. The relationship between upper and lower airways described in humans by the "one airway, one disease" concept might also apply to horses. Objective: To evaluate if an association exists between endoscopic inflammatory scores and mucus scores of upper and lower airways and to investigate if endoscopic findings correlate with the lower airway inflammation measured by bronchoalveolar lavage (BAL) cytology. Methods: Prospective field study. Pharyngit...
Abraham G, Zizzadoro C, Kacza J, Ellenberger C, Abs V, Franke J, Schoon HA, Seeger J, Tesfaigzi Y, Ungemach FR.Horses develop recurrent airway obstruction (RAO) that resembles human bronchial asthma. Differentiated primary equine bronchial epithelial cells (EBEC) in culture that closely mimic the airway cells in vivo would be useful to investigate the contribution of bronchial epithelium in inflammation of airway diseases. However, because isolation and characterization of EBEC cultures has been limited, we modified and optimized techniques of generating and culturing EBECs from healthy horses to mimic in vivo conditions. Results: Large numbers of EBEC were obtained by trypsin digestion and successfull...
Eder C, Crameri R, Mayer C, Eicher R, Straub R, Gerber H, Lazary S, Marti E.Immunoglobulin E antibody (IgE) levels against four recombinant (r) mould allergens (r-Aspergillus fumigatus [rAsp f] 7, 8 and 9; r-Alternaria alternata 1 [rAlta1]) and crude mould (Aspergillus fumigatus, Alternaria alternata, Penicillium notatum) and storage mite extracts were determined by ELISA in sera from 24 pulmonary sound control horses and 26 horses suffering from chronic bronchitis/bronchiolitis (CB), also called chronic obstructive pulmonary disease (COPD). Serum IgG and IgA titres were also determined against Aspergillus fumigatus extract and rAsp f 8.IgE against the crude extracts ...
Franke J, Abs V, Zizzadoro C, Abraham G.Airway fibroblasts have become a critical addition to all facets of structural lung tissue changes such as in human asthma and chronic obstructive pulmonary disease, but little is known about their role in the equine recurrent airway obstruction, a disease that resembles to the human asthma. Since the equine bronchial fibroblasts (EBF) have not been isolated and characterized yet, the use of defined medium was investigated. Results: Primary EBF were cultured on non-collagen coated flasks without serum or in the presence of fetal bovine serum (FBS) or horse serum (HS) or in serum depleted mediu...
Bullone M, Beauchamp G, Godbout M, Martin JG, Lavoie JP.Endobronchial ultrasonography (EBUS) revealed differences in the thickness of the layer representing subepithelial tissues (L2) between human asthmatics and controls, but whether this measurement correlates with airway smooth muscle (ASM) remodeling in asthma is unknown. In this study, we sought to determine the ability of EBUS to predict histological ASM remodeling in normal and equine asthmatic airways. We studied 109 isolated bronchi from the lungs of 13 horses. They underwent EBUS examination using a 30 MHz radial probe before being processed for histology. ASM remodeling parameters were e...
Bullone M, Lavoie JP.Human asthma is a complex and heterogeneous disorder characterized by chronic inflammation, bronchospasm and airway remodeling. The latter is a major determinant of the structure-function relationship of the respiratory system and likely contributes to the progressive and accelerated decline in lung function observed in patients over time. Corticosteroids are the cornerstone of asthma treatment. While their action on inflammation and lung function is well characterized, their effect on remodeling remains largely unknown. An important hindrance to the study of airway remodeling as a major focu...
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 ...
Johnson JA, Prescott JF, Markham RJ.Six foals were inoculated intrabronchially with a suspension of Corynebacterium equi. Six weeks before this challenge, three foals were vaccinated with a C. equi bacterin. Three foals were unvaccinated controls. All foals developed a severe bronchopneumonia in the inoculated lung, indicating that vaccination was not protective. Three foals (two vaccinated, one control) were killed eight to nine days after infection. One control died on day 9 with lesions of disseminated intravascular coagulation. The remaining two foals (one vaccinated, one control) were killed on day 17. C. equi was cultured ...
McGorum BC, Ellison J, Cullen RT.The concentrations of total and respirable airborne endotoxin in the breathing zone of a pony in 3 different management systems, on 8 occasions, are reported. Airborne endotoxin concentrations in all 3 systems were lower than those reported for many other agricultural environments. However, total airborne endotoxin concentrations in many of the conventional stables exceeded those which can induce pulmonary inflammation and bronchial hyper-responsiveness in normal human subjects, and exceeded those which can induce bronchoconstriction in humans with pre-existing pulmonary inflammation. Therefor...
Barton AK, Shety T, Bondzio A, Einspanier R, Gehlen H.In chronic respiratory disease, matrix metalloproteinases (MMPs) contribute to pathological tissue destruction when expressed in excess, while tissue inhibitors of metalloproteinases (TIMPs) counteract MMPs with overexpression leading to fibrosis formation. They may be out of balance in equine pneumopathies and serve as biomarkers of pulmonary inflammation. We hypothesized that MMPs and TIMPs correlate to clinical findings and bronchoalveolar lavage fluid cytology in different equine chronic pneumopathies. Using a scoring system, 61 horses were classified controls as free of respiratory diseas...
Lavoie JP, Léguillette R, Pasloske K, Charette L, Sawyer N, Guay D, Murphy T, Hickey GJ.To evaluate whether the leukotriene (LT) D4 receptor antagonist L-708,738 is therapeutically beneficial in treating horses with recurrent airway obstruction (heaves). Methods: 12 adult horses with heaves and healthy lung lobes from 20 slaughtered horses. Methods: Lung lobes were used for smooth muscle tension and radioligand binding studies. Horses with heaves were given a placebo for 14 days and administered L-708,738 (n = 6; 2.5 mg/kg PO, q 12 h) or dexamethasone (6; 0.04 mg/kg, IV, q 24 h) from days 14 to 28. Pulmonary function was measured weekly for 36 days, and bronchoalveolar cells were...
Chand N, Eyre P.Histamine, 2-methylhistamine (a specific H1-agonist), 5-HT, PGF2alpha, SRS-A, bradykinin (BK) and carbachol contract bronchial and tracheal smooth muscles of the horse. Isoprenaline, PGE1, E2, dimaprit and 4-methylhistamine (last two = specific H2-agonists) relaxed airways which were partially contracted to carbachol. Mepyramine (a specific H1-antagonist) selectively antagonized contractions to histamine. In the presence of mepyramine, histamine caused relaxation of airways partially contracted to carbachol. Metiamide and burimamide (specific H2-antagonists) specifically antagonized or reverse...
Jacks S, Giguère S, Crawford PC, Castleman WL.Rhodococcus equi is a facultative intracellular pathogen that causes pneumonia in young foals but does not induce disease in immunocompetent adult horses. Clearance of R. equi depends mainly on gamma interferon (IFN-gamma) production by T lymphocytes, whereas the predominance of interleukin 4 (IL-4) is detrimental. Young foals, like neonates of many other species, are generally deficient in the ability to produce IFN-gamma. The objective of this study was to compare the cytokine profiles, as well as cell-mediated and antibody responses, of young foals to those of adult horses following intrabr...
Fortier G, van Erck E, Fortier C, Richard E, Pottier D, Pronost S, Miszczak F, Thiry E, Lekeux P.The objectives of this study were to estimate the prevalence and the potential role of equine herpesviruses (EHVs) detection in both bronchoalveolar lavage (BAL) and tracheal wash (TW). The population included a control group (CTL; 37 TW and 25 BAL) and a pathological group (PAT; 259 TW and 387 BAL), including horses either suffering from respiratory diseases including syndrome of tracheal inflammation, inflammatory airway disease, recurrent airway obstruction, or submitted to respiratory investigation because of exercise intolerance or poor performance. Each respiratory liquid was submitted t...
Muscatello G, Gerbaud S, Kennedy C, Gilkerson JR, Buckley T, Klay M, Leadon DP, Browning GF.Rhodococcoccus equi is a significant cause of bronchopneumonia in foals worldwide. Infection of the lungs is believed to result from inhalation of virulent R. equi in dust from contaminated environments. A measure of infectious risk in an environment is the level of airborne contamination. Objective: To assess and compare the level of airborne virulent R. equi in paddocks and stables. Methods: Air samples were collected sequentially over the 2003 foaling season from the paddocks and stables on 3 Irish horse breeding farms affected by R. equi pneumonia. Colony blotting and DNA hybridisation tec...
