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.
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...
Sengupta PP, Rudramurthy GR, Ligi M, Roy M, Balamurugan V, Krishnamoorthy P, Nagalingam M, Singh L, Rahman H.Trypanosoma evansi, a haemoflagellate, causes "surra" an important chronic wasting disease of a wide range of wild and domestic herbivorous and carnivorous animals including cattle, buffaloes, camels, horses, etc. The untreated recovered animal can act as a carrier without exhibiting the disease symptoms and can be a source of infection to healthy animals. The diagnosis and subsequent treatment of the carrier animals is helpful to curb the disease. As the parasitaemia in carrier animals is very scanty, the conventional blood smear examination, which is widely practiced in the field, cannot det...
Dubuc J, Lavoie JP.The objective of this study was to determine whether eosinophils infiltrate the airway wall of horses with heaves. Eosinophils were evaluated using paraffin embedded lung tissues from six heaves-affected horses in crisis and six aged-matched controls. Slides were stained using Luna's method and eosinophils enumerated using histomorphometric techniques. Total eosinophil counts (expressed per mm(2) of basement membrane) were significantly higher in the airways of controls horses than in horses with heaves. Intraluminal, intraepithelial, and airway smooth muscle eosinophils counts were also incre...
Franke J, Abraham G.Altered airway cell proliferation plays an important role in the pathogenesis of human bronchial asthma and chronic obstructive pulmonary disease (COPD) as well as the equine recurrent airway obstruction (RAO) with consistent changes, i.e. narrowing the airway wall, explained by proliferation and differentiation of fibroblasts. In permanent cell lines, it has been suggested that β2-adrenoceptor agonists and glucocorticoids regulate cell proliferation via the β2-adrenoceptor pathway; indeed, no study was carried out in fresh isolated primary equine bronchial fibroblasts (EBF). We characterize...
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...
Rettmer H, Hoffman AM, Lanz S, Oertly M, Gerber V.In clinical practice, veterinarians often depend on owner-reported signs to assess the clinical course of horses with recurrent airway obstruction (RAO). Objective: To test whether owner-reported information on frequency of coughing and observation of nasal discharge are associated with clinical, cytological and bronchoprovocation findings in RAO-affected horses in nonstandardised field conditions. Methods: Cross-sectional study comparing healthy and RAO-affected horses. Methods: Twenty-eight healthy and 34 RAO-affected Swiss Warmblood horses were grouped according to owner-reported 'coughing ...
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...
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...
Gerber V, Tessier C, Marti E.Genetic predispositions for guttural pouch tympany, recurrent laryngeal neuropathy and recurrent airway obstruction (RAO) are well documented. There is also evidence that exercise-induced pulmonary haemorrhage and infectious diseases of the respiratory tract in horses have a genetic component. The clinical expression of equine respiratory diseases with a genetic basis results from complex interactions between the environment and the genetic make-up of each individual horse. The genetic effects are likely to be due to variations in several genes, i.e. they are polygenic. It is therefore unlikel...
Sheats MK, Pescosolido KC, Hefner EM, Sung EJ, Adler KB, Jones SL.Neutrophil infiltration is a prominent feature in a number of pathologic conditions affecting horses including recurrent airway obstruction, ischemia-reperfusion injury, and laminitis. Cell signaling components involved in neutrophil migration represent targets for novel anti-inflammatory therapies. In order to migrate into tissue, neutrophils must respond to chemoattractant signals in their external environment through activation of adhesion receptors (i.e. integrins) and reorganization of the actin cytoskeleton. Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS), a highly conserved actin...
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...
de Lagarde M, Rodrigues N, Chevigny M, Beauchamp G, Albrecht B, Lavoie JP.Bronchospasm results in airway obstruction in horses with heaves. Atropine is the most potent bronchodilator drug currently available for horses, but is associated with side effects that limit its use. Like atropine, N-butylscopolammonium bromide (NBB) is an anticholinergic agent with bronchodilatory properties. Objective: To compare the bronchodilating effects and side effects of atropine and NBB in horses with heaves. Methods: Cross-over experiment using horses with heaves. Methods: Eight horses with heaves were administered atropine and NBB, using a cross-over design. Heart rate, pupillary ...
Hansen S, Baptiste KE, Fjeldborg J, Betancourt A, Horohov DW.An imbalance in various cytokine mRNA expression in bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) in horses suffering from recurrent airway obstruction (RAO) has been demonstrated; however, the natural variation of cytokine expression in healthy horses has yet to be described. The objectives of this study were to: (1) identify age-related differences in the expression of pro-inflammatory cytokines in BAL and PBMC, (2) compare the expression of pro-inflammatory cytokines between BAL and PBMC, and (3) evaluate the relationship between BAL pro-inflammatory cytokine ex...
Niedzwiedz A, Jaworski Z, Tykalowski B, Smialek M.Dysregulation of apoptosis has been implicated in a range of diseases including tumors, neurodegenerative and autoimmune diseases, as well as allergic asthma and chronic obstructive pulmonary disease (COPD) in humans. Although it has a different pathophysiology, delayed apoptosis of various inflammatory cells may play a pivotal role in the development of recurrent airway obstruction (RAO) in horses. Reduction of inflammatory cell apoptosis or a dysregulation of this process could lead to chronic inflammation and tissue injury. Therefore, the aim of this study was to investigate the rate of apo...
Bosshard S, Gerber V.It is often assumed that horses with mild respiratory clinical signs, such as mucous nasal discharge and occasional coughing, have an increased risk of developing recurrent airway obstruction (RAO). Objective: Compared to horses without any clinical signs of respiratory disease, those with occasional coughing, mucous nasal discharge, or both have an increased risk of developing signs of RAO (frequent coughing, increased breathing effort, exercise intolerance, or a combination of these) as characterized by the Horse Owner Assessed Respiratory Signs Index (HOARSI 1-4). Methods: Two half-sibling ...
Henríquez C, Perez B, Morales N, Sarmiento J, Carrasco C, Morán G, Folch H.Recurrent airway obstruction (RAO) is an equine immune-mediated disease with a high incidence worldwide. The aim of this work was to contribute to the understanding of RAO pathogenesis by studying T cells bearing regulatory markers in peripheral blood (PB) and in bronchoalveolar lavage fluid (BALF) recovered from the same group of susceptible horses before and after exposure to moldy hay, which has been shown to induce RAO signology in our horse herd. With this purpose, mononuclear cells were obtained from the BALF and PB from horses before and after antigenic challenge and were stained with f...
Pirie RS.Recurrent airway obstruction is a widely recognised airway disorder, characterised by hypersensitivity-mediated neutrophilic airway inflammation and lower airway obstruction in a subpopulation of horses when exposed to suboptimal environments high in airborne organic dust. Over the past decade, numerous studies have further advanced our understanding of different aspects of the disease. These include clarification of the important inhaled airborne agents responsible for disease induction, improving our understanding of the underlying genetic basis of disease susceptibility and unveiling the fu...
Shaba JJ, Behan Braman A, Robinson NE.In many inflammatory diseases plasma cortisol concentration (CORT) increases at the onset of acute inflammation, but the situation in recurrent airway obstruction (RAO) of horses is unknown. Methods: Split-plot repeated measures design with one grouping factor (disease) and two repeated factors (day and 3-hour intervals). Objective: To test the hypothesis that CORT increases as acute exacerbations of RAO develop. Methods: Four RAO-susceptible and 4 control horses were placed in a low dust environment (LDEnv) for 2 days followed by 2 days in a high dust environment (HDEnv). Exacerbations of RAO...
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...
Lanz S, Gerber V, Marti E, Rettmer H, Klukowska-Rötzler J, Gottstein B, Matthews JB, Pirie S, Hamza E.Equine recurrent airway obstruction (RAO) is an inflammatory, obstructive airway disease induced by exposure of susceptible horses to inhaled organic dust particles. The immunological process underlying RAO is still unclear. Previous studies have shown that RAO is linked to the Interleukin-4 receptor (IL-4R) gene in one Warmblood family (F1), but not in another (F2). It has also been shown that in F1, but not in F2, RAO is associated with resistance against parasites, suggesting that this association may have an immuno-genetic basis. Therefore, we hypothesized that the T helper (h)1/Th2/regula...
Sarmiento J, Perez B, Morales N, Henriquez C, Vidal L, Folch H, Galecio JS, Morán G.A reduction in inflammatory cell apoptosis is an important concept in the maintenance of inflammation and a potential target for the resolution of inflammation in many inflammatory diseases. Dysregulation of apoptosis has been implicated in a range of diseases, including tumors, neurodegenerative disorders and autoimmunity, and may also be implicated in allergic asthma. In horses, recurrent airway obstruction (RAO) is an asthma-like condition that is characterized increased survival neutrophil bronchial. Tamoxifen is a synthetic, non-steroidal, anti-estrogen agent that is widely used for treat...
Haltmayer E, Reiser S, Schramel JP, van den Hoven R.The aim of the study was to show that changes in thoracoabdominal asynchrony (TAA) between quiet breathing and CO2-induced hyperpnoea can be used to differentiate between horses with healthy airways and those suffering from inflammatory airway disease (IAD) or recurrent airway obstruction (RAO). The level of TAA was displayed by the Pearson's correlation coefficient (PCC) of thoracic and abdominal signals, generated by respiratory ultrasonic plethysmography (RUP) during quiet breathing and hyperpnoea. Changes in TAA were expressed as the quotient of the PCCs (PCCQ) during normal breathing and ...
Wagner B, Ainsworth DM, Freer H.Soluble CD14 (sCD14) binds bacterial lipopolysaccharide (LPS) and acts as an anti-inflammatory LPS-inhibitor in vivo. In humans, sCD14 is one of the soluble biomarkers used for various inflammatory diseases and conditions, however, sCD14 assays have not yet been evaluated in horses. Here, we developed and optimized a bead-based assay for the quantification of sCD14 in horses. The assay was then used to determine native sCD14 concentrations in serum from healthy and septic foals, in the colostrum of healthy mares and in plasma from adult horses with recurrent airway obstruction (RAO) and contro...
Behan AL, Hauptman JG, Robinson NE.To use noninvasive respiratory inductance plethysmography (RIP) to investigate differences in breathing patterns between horses with and without recurrent airway obstruction (RAO) during the onset of airway obstruction induced through confinement to stables. Methods: 12 horses with no history or clinical signs of respiratory disease (control horses) and 7 RAO-affected horses. Methods: The study involved 2 phases. In phase 1, the optimal position of RIP bands for recording pulmonary function was investigated in 12 control horses. In phase 2, 7 RAO-affected and 7 control horses were confined to ...
Côté O, Lillie BN, Hayes MA, Clark ME, van den Bosch L, Katavolos P, Viel L, Bienzle D.Secretoglobin 1A1 (SCGB 1A1), also called Clara cell secretory protein, is the most abundantly secreted protein of the airway. The SCGB1A1 gene has been characterized in mammals as a single copy in the genome. However, analysis of the equine genome suggested that horses might have multiple SCGB1A1 gene copies. Non-ciliated lung epithelial cells produce SCGB 1A1 during inhalation of noxious substances to counter airway inflammation. Airway fluid and lung tissue of horses with recurrent airway obstruction (RAO), a chronic inflammatory lung disease affecting mature horses similar to environmental...
Stopyra A, Sobiech P, Waclawska-Matyjasik A.The acid-base equilibrium is closely linked to gas exchange in the lungs, and respiratory exchange ratios are used to evaluate respiratory effectiveness and tissue oxygen levels. Acid-base indicators are determined in both arterial and venous blood samples. This study compares the usefulness of acid-base indicators of venous and arterial blood in monitoring the condition of horses with recurrent airway obstruction. Prior to treatment involving bronchodilating glucocorticoids, expectorant and mucolytic drugs, more pronounced changes were observed in venous blood (pH 7.283, pCO2 61.92 mmHg, pO2 ...
Wilson ME, Berney C, Behan AL, Robinson NE.Lidocaine decreases neutrophilic inflammation in models of acute lung injury and decreases inflammation in asthmatic patients. Neutrophilic bronchiolitis develops in recurrent airway obstruction (RAO), but it remains unknown if lidocaine infusion decreases neutrophil migration into the airways. Objective: Lidocaine decreases neutrophilic inflammation as measured in BALF in RAO-affected horses. Methods: Six RAO-susceptible horses in remission. Methods: In a randomized cross-over design, horses received lactated Ringer's solution (LRS) IV or lidocaine hydrochloride IV with a minimum of 4 weeks a...
Onmaz AC, Stoklas-Schmidt C, van den Hoven R.The aim of the study was to analyse the day-to-day variability of the respiratory resistance (R(rs)) and the reactance (X(rs)) in 5 horses in a status of remission of recurrent airway obstruction by forced oscillometry system (FOS). Furthermore, the effects of stabling, outdoor and room temperature and humidity on these parameters were determined. Mean R(rs) at oscillation frequencies 1, 1.5, 2 and 3 Hz were all significantly higher in the morning than in the afternoon, while X(rs) was not significantly affected by time of the day. R(rs) was significantly different on various sampling days at ...
Fugazzola M, Barton AK, Niedorf F, Kietzmann M, Ohnesorge B.Glucocorticoids have been proven to be effective in the therapy of recurrent airway obstruction (RAO) in horses via systemic as well as local (inhalative) administration. Elective analysis of the effects of this drug on bronchoconstriction in viable lung tissue offers an insight into the mechanism of action of the inflammatory cascade occurring during RAO which is still unclear. The mechanism of action of steroids in treatment of RAO is thought to be induced through classical genomic pathways. We aimed at electively studying the effects of the glucocorticoid beclomethasone dipropionate on equi...
Couetil L, Hammer J, Miskovic Feutz M, Nogradi N, Perez-Moreno C, Ivester K.Equine recurrent airway obstruction (RAO) is characterized by airway inflammation, bronchoconstriction, and increased mucus production in the airways. Anticholinergic drugs like atropine induce bronchodilatation and rapid improvement in lung function. N-butylscopolammonium bromide (NBB) is an anticholinergic drug used to relieve spasmodic colic in horses, but its effect on airway smooth muscle is unknown. Objective: To evaluate the effect of NBB on clinical signs and lung function of RAO-affected horses. Methods: Nine horses diagnosed with RAO. Methods: Double-blind, placebo-controlled, random...
Jackson CA, Berney C, Jefcoat AM, Robinson NE.Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional...
Zucca E, Corsini E, Galbiati V, Lange-Consiglio A, Ferrucci F.Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lu...
Klier J, May A, Fuchs S, Schillinger U, Plank C, Winter G, Gehlen H, Coester C.Recurrent airway obstruction (RAO) in horses has become a common problem in stabled horses in industrialized countries and deserves new therapeutic strategies. CpG-oligodeoxynucleotides (CpG-ODNs) were developed as effective immunostimulating agents to induce a Th2/Th1 shift. These agents showed a beneficial therapeutic effect in allergic diseases with predominant Th2 immunoresponse. CpG-ODN delivery by gelatin nanoparticles (GNPs) resulted in enhanced cellular uptake in murine and human in vitro studies and was a starting point for the present trial. The aim of this study was to identify an o...
Berndt A, Derksen FJ, Venta PJ, Ewart S, Yuzbasiyan-Gurkan V, Robinson NE.Recurrent airway obstruction (RAO) is characterized by neutrophilic airway inflammation and obstruction, and stabling of susceptible horses triggers acute disease exacerbations. Stable dust is rich in endotoxin, which is recognized by Toll-like receptor (TLR) 4. In human bronchial epithelium, TLR4 stimulation leads to elevation of interleukin (IL)-8 mRNA expression. The zinc finger protein A20 negatively regulates this pathway. We hypothesized that TLR4 and IL-8 mRNA and neutrophil numbers are elevated and that A20 mRNA is not increased in RAOs during stabling compared with controls and with R...
Gerber V, Robinson NE, Venta RJ, Rawson J, Jefcoat AM, Hotchkiss JA.Increased mucin gene expression may be an important cause of mucus accumulation observed in recurrent airway obstruction (RAO)-affected horses. To date, however, no mucin gene sequences are available for the horse. Objective: To identify equine homologues of gel-forming mucins and investigate their expression at different airway generations of healthy and RAO-affected horses. Methods: Two equine homologues were identified by cloning and sequencing fragments of equine (eq)MUC5AC and eqMUC2. Results: Semiquantitative RT-PCR on RNA from airways (generations 1, 5, 10, 15; small airways and parench...
Bullone M, Hélie P, Joubert P, Lavoie JP.Remodeling of the peripheral airways persists during the asymptomatic phase of heaves. Assessing the histology of large bronchi could facilitate the diagnosis of heaves during remission of the disease. Objective: Airway inflammation and remodeling in endobronchial biopsy (EBB) specimens differentiate horses with heaves from controls, independently of their clinical status (exacerbation or remission). Methods: Fourteen healthy horses and 24 horses with heaves. Methods: A 14-point scoring system assessing central bronchial wall inflammation and remodeling was developed. The score was validated b...
Costa LR, Johnson JR, Baur ME, Beadle RE.To describe the seasonal pattern of clinical exacerbation of summer pasture-associated recurrent airway obstruction (SPA-RAO) in relation to climate and aeroallergens in horses. Methods: 19 horses with SPA-RAO and 10 nonaffected horses. Methods: Daily examinations were performed on all horses while they were kept on pasture for 3 years. Onset and progression of clinical exacerbation based on a clinical score of respiratory effort were evaluated in relation to changes in maximum temperature, minimum temperature, mean temperature, maximum dew-point temperature, minimum dew-point temperature, and...
Pirie RS, Dixon PM, McGorum BC.Mould extract inhalation challenges have been used extensively in the investigation of heaves. Such challenges have induced pulmonary neutrophilic inflammation and dysfunction, consistent with, but less severe than the natural disease. However, the method of mould extract production is likely to result in endotoxin contamination. Objective: To investigate whether insufficient dose delivery was responsible for the shortfall in response to inhaled extract compared with natural disease, and whether endotoxin contamination of mould extract contributed to the pulmonary inflammation and dysfunction....
Deaton CM, Marlin DJ, Smith NC, Roberts CA, Harris PA, Schroter RC, Kelly FJ.Inhaled ozone can induce oxidative injury and airway inflammation. Horses affected by recurrent airway obstruction (RAO) have a decreased pulmonary antioxidant capacity, which may render them more susceptible to oxidative challenge. It is currently unknown whether RAO-affected horses are more susceptible to oxidative stress than those unaffected by RAO. Objective: To determine whether ozone exposure induces greater oxidative stress and airway inflammation in RAO-affected horses in remission than in healthy horses. Methods: Seven healthy control horses and 7 RAO-affected horses were exposed to ...
Grzyb J, Podstawski Z, Bulski K.Keeping horses in good condition requires providing them with living conditions that meet welfare requirements. These animals should be accommodated with suitable space, access to high nutritional fodder and water, and a suitable microclimate in their shelters. When it comes to the environment in the stables, a serious problem is created by particulate matter (PM), which consists of bacteria. PM concentration may be responsible for developing multiple lower respiratory tract diseases in horses, including allergies and recurrent airway obstruction (RAO). In turn, these ailments may lead to decr...
Matera MG, Calzetta L, Rogliani P, Bardaro F, Page CP, Cazzola M.Equine obstructive pulmonary disease, also known as heaves or recurrent airway obstruction (RAO) is a common equine pulmonary disease with some similarities to human asthma and COPD, which represents a major cause of morbidity and loss of lung performance. Salbutamol has been widely used for the treatment of human airway diseases and has usually been prepared as the racemic form of the drug. However, recently the R-enantiomer of salbutamol has been introduced into clinical practice in the treatment of asthma in humans and this has been suggested to be an improvement on the racemic form of the ...
Klier J, Fuchs S, May A, Schillinger U, Plank C, Winter G, Coester C, Gehlen H.In the recent years, nanotechnology has boosted the development of potential drug delivery systems and material engineering on nanoscale basis in order to increase drug specificity and reduce side effects. A potential delivery system for immunostimulating agents such as cytosine-phosphate-guanine-oligodeoxynucleotides (CpG-ODN) needs to be developed to maximize the efficacy of immunotherapy against hypersensitivity. In this study, an aerosol formulation of biodegradable, biocompatible and nontoxic gelatin nanoparticle-bound CpG-ODN 2216 was used to treat equine recurrent airway obstruction in ...
Klukowska-Rötzler J, Swinburne JE, Drögemüller C, Dolf G, Janda J, Leeb T, Gerber V.Recurrent airway obstruction (RAO) in horses is the result of an interaction of genetic and environmental factors and shares many characteristics with human asthma. Many studies have suggested that the interleukin-4 receptor gene (IL4R) is associated with this disease, and a QTL region on chromosome 13 containing IL4R was previously detected in one of the two Swiss Warmblood families. We sequenced the entire IL4R gene in this family and detected 93 variants including five non-synonymous protein-coding variants. The allele distribution at these SNPs supported the previously detected QTL signal....
Katavolos P, Ackerley CA, Clark ME, Bienzle D.Horses suffer from recurrent airway obstruction, an asthma-like condition induced by repeat inhalation of environmental substances present in barn air. Clara cell secretory protein (CCSP) is much reduced during active inflammation when neutrophils predominate in the airways, and in chronic asthmatics. We sought to investigate morphologic and functional interactions of CCSP with neutrophils. Bronchoalveolar and blood neutrophils from healthy control animals, and from animals with recurrent airway obstruction in remission and exacerbation, were evaluated by immuno-cytochemistry and immuno-electr...
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...
Côté O, Lillie BN, Hayes MA, Clark ME, van den Bosch L, Katavolos P, Viel L, Bienzle D.Secretoglobin 1A1 (SCGB 1A1), also called Clara cell secretory protein, is the most abundantly secreted protein of the airway. The SCGB1A1 gene has been characterized in mammals as a single copy in the genome. However, analysis of the equine genome suggested that horses might have multiple SCGB1A1 gene copies. Non-ciliated lung epithelial cells produce SCGB 1A1 during inhalation of noxious substances to counter airway inflammation. Airway fluid and lung tissue of horses with recurrent airway obstruction (RAO), a chronic inflammatory lung disease affecting mature horses similar to environmental...
de Lagarde M, Rodrigues N, Chevigny M, Beauchamp G, Albrecht B, Lavoie JP.Bronchospasm results in airway obstruction in horses with heaves. Atropine is the most potent bronchodilator drug currently available for horses, but is associated with side effects that limit its use. Like atropine, N-butylscopolammonium bromide (NBB) is an anticholinergic agent with bronchodilatory properties. Objective: To compare the bronchodilating effects and side effects of atropine and NBB in horses with heaves. Methods: Cross-over experiment using horses with heaves. Methods: Eight horses with heaves were administered atropine and NBB, using a cross-over design. Heart rate, pupillary ...
Jose-Cunilleras E, Kohn CW, Hillier A, Saville WJ, Lorch G.To compare responses to a variety of intradermally injected allergens among healthy horses and horses with chronic obstructive pulmonary disease (COPD), recurrent urticaria (RU), and atopic dermatitis-insect hypersensitivity (allergic dermatitis [AD]). Methods: Case-control study. Methods: 86 horses. Methods: Results of intradermal testing for horses with COPD, RU, or AD were compared with results for healthy horses. Results: Compared with healthy horses, horses with COPD, RU, and AD were significantly more likely to have positive (> or = 3+) reactions to intradermal allergens (molds, weeds, t...
Borlone C, Morales N, Henriquez C, Folch H, Olave C, Sarmiento J, Uberti B, Moran G.Neutrophils participate in innate immunity as the first line of host defense against microorganisms. However, exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous preliminary studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apop...
Klier J, Lehmann B, Fuchs S, Reese S, Hirschmann A, Coester C, Winter G, Gehlen H.Recurrent airway obstruction (RAO), an asthma-like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN) are known to direct the immune system toward a Th1-pathway, and away from the pro-allergic Th2-line (Th2/Th1-shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG-ODN against nuclease degeneration. Prelimi...
Barussi FC, Bastos FZ, Leite LM, Fragoso FY, Senegaglia AC, Brofman PR, Nishiyama A, Pimpão CT, Michelotto PV.This research evaluated the effects of bone marrow-derived mononuclear cells (BMMCs) on the inflammatory process in the equine recurrent airway obstruction (RAO). Eight horses in RAO clinical score were divided into cell therapy group (Gcel) treated with a single intratracheal dose of BMMCs, and dexamethasone group (Gdex) treated with 21days of oral dexamethasone. The horses were clinically revaluated on days 7 and 21, together with cytological evaluation of the BALF, and detection of inflammatory markers (interleukins [IL]-10, -4, and -17, and interferon γ and α). There were decreases in re...
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 ...
Sarmiento J, Perez B, Morales N, Henriquez C, Vidal L, Folch H, Galecio JS, Morán G.A reduction in inflammatory cell apoptosis is an important concept in the maintenance of inflammation and a potential target for the resolution of inflammation in many inflammatory diseases. Dysregulation of apoptosis has been implicated in a range of diseases, including tumors, neurodegenerative disorders and autoimmunity, and may also be implicated in allergic asthma. In horses, recurrent airway obstruction (RAO) is an asthma-like condition that is characterized increased survival neutrophil bronchial. Tamoxifen is a synthetic, non-steroidal, anti-estrogen agent that is widely used for treat...
Ghosh S, Das PJ, McQueen CM, Gerber V, Swiderski CE, Lavoie JP, Chowdhary BP, Raudsepp T.We explored the involvement of genomic copy number variants (CNVs) in susceptibility to recurrent airway obstruction (RAO), or heaves-an asthmalike inflammatory disease in horses. Analysis of 16 RAO-susceptible (cases) and six RAO-resistant (control) horses on a custom-made whole-genome 400K equine tiling array identified 245 CNV regions (CNVRs), 197 previously known and 48 new, distributed on all horse autosomes and the X chromosome. Among the new CNVRs, 30 were exclusively found in RAO cases and were further analyzed by quantitative PCR, including additional cases and controls. Suggestive as...
Couëtil LL, Chilcoat CD, DeNicola DB, Clark SP, Glickman NW, Glickman LT.To determine whether administration of glucocorticoids provides additional benefits to environmental management of horses with recurrent airway obstruction (RAO). Methods: 28 horses with RAO. Methods: Horses were classified as having mild, moderate, or severe RAO. Within each category, horses were randomly assigned to receive inhaled fluticasone propionate, inhaled control substance, or oral administration of prednisone. During the 4-week study, horses were maintained outdoors and fed a pelleted feed. Clinical scores, pulmonary function, results of cytologic examination of bronchoalveolar lava...
Couëtil LL, Art T, de Moffarts B, Becker M, Mélotte D, Jaspar F, Bureau F, Lekeux P.Glucocorticoid (GC) therapy is recognized to be effective for the treatment of recurrent airway obstruction (RAO) in horses. Anti-inflammatory properties of GC are thought to be mediated by suppression of inflammatory gene expression via inhibition of transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). The purpose of this study was to evaluate the effect of low-dose inhaled beclomethasone dipropionate and injectable dexamethasone 21-isonicotinate on clinical signs, pulmonary function, airway cytology, and activity of NF-kappaB and AP-1 in bronchial c...
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...
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...
Hoffman AM, Oura TJ, Riedelberger KJ, Mazan MR.Horses with recurrent airway obstruction (heaves) are described as exhibiting "increased abdominal effort," but it is unknown whether this translates to an effective contribution to ventilation. Objective: We hypothesized that heaves is characterized by asynchrony between rib cage and abdominal motions, and that the abdominal component is the major contributor to ventilation. Methods: The rib cage versus abdominal motion in naturally occurring heaves (n = 15) was compared to controls at rest (n = 7) and during hyperpnea because of lobeline treatment, and the effects of histamine-induced bronch...
