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.
Propofol protects against opioid-induced hyperresponsiveness of airway smooth muscle in a horse model of target-controlled infusion anaesthesia. General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contra...
Endobronchial Ultrasound Reliably Quantifies Airway Smooth Muscle Remodeling in an Equine Asthma Model. 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...
Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma. Recurrent airway obstruction (RAO) is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs). We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two h...
Relationships between equine airway reactivity measured by flowmetric plethysmography and specific indicators of airway inflammation in horses with suspected inflammatory airway disease. Agreement between airway reactivity measured by flowmetric plethysmography and histamine bronchoprovocation, and lower airway inflammation measured by bronchoalveolar lavage (BAL) cytology, has not been studied in horses with suspected inflammatory airway disease (IAD). Objective: We tested the hypothesis that airway reactivity is associated with BAL cytology in horses presenting for unexplained poor performance and/or chronic cough. Methods: Prospective clinical study. Methods: Forty-five horses, predominantly young Standardbred racehorses, presenting for unexplained poor performance or chron...
Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in heaves, an asthma-like disease of horses. Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription factor that regulates myocyte differentiation in vitro in vascular and intestinal smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes ASM proliferation while binding to myocardin (MYOCD) leading to the expression of contractile elements in these tissues. The objective of this study was therefore to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from central and peripheral airways in heaves, ...
Pollen Allergies in Humans and their Dogs, Cats and Horses: Differences and Similarities. Both humans and their most important domestic animals harbor IgE and a similar IgE receptor repertoire and expression pattern. The same cell types are also involved in the triggering or regulation of allergies, such as mast cells, eosinophils or T-regulatory cells. Translational clinical studies in domestic animals could therefore help cure animal allergies and at the same time gather knowledge relevant to human patients. Dogs, cats and horses may spontaneously and to different extents develop immediate type symptoms to pollen allergens. The skin, nasal and bronchial reactions, as well as chro...
Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study. 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...
Expression of surface platelet receptors (CD62P and CD41/61) in horses with recurrent airway obstruction (RAO). Recurrent airway obstruction (RAO) is an allergic disease of horses similar to human asthma, which is characterized by airway inflammation and activation of neutrophils, lymphocytes and platelets. Platelet activation and an increase in circulating platelet-leukocyte aggregates may lead to airway remodeling. The aim of this study was to investigate platelet status in RAO-affected horses based on the platelet morphology and platelet surface expression of CD41/61 and CD62P. Ten RAO-affected horses and ten healthy horses were included in this study. Blood samples were obtained to determine the pla...
Asthma “of horses and men”–how can equine heaves help us better understand human asthma immunopathology and its functional consequences? Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, while experiments in which the disease is artificially induced have helped discovering biological and molecular pathways leading to allergic airway inflammation, their contribution to the understanding of the causality of the disease has been more limited. Horses naturally suffer from an asthma-like condition called "heaves" which presents sticking similarities with human asthma. It is characterized by reversible airway obstruction, airway neutrophilic inflammation, an...
Serum cortisol concentration in horses with heaves treated with fluticasone proprionate over a 1 year period. The purpose of this study is to measure the effect of long-term administration of inhaled fluticasone proprionate on cortisol concentrations in heaves-affected horses. Eleven horses with heaves were treated with fluticasone at least once daily at dosages required to improve lung function or with antigen avoidance alone for 1 year. Morning serum cortisol was measured before and after 10, 30, 110, 190, 230, 280, and 320 days of treatment. Cortisol was also measured in the afternoon of day 330. Cortisol was significantly lower in the Fluticasone group on days 30, 110, and 190 when compared with t...
Comparative immunology of allergic responses. Allergic responses occur in humans, rodents, non-human primates, avian species, and all of the domestic animals. These responses are mediated by immunoglobulin E (IgE) antibodies that bind to mast cells and cause release/synthesis of potent mediators. Clinical syndromes include naturally occurring asthma in humans and cats; atopic dermatitis in humans, dogs, horses, and several other species; food allergies; and anaphylactic shock. Experimental induction of asthma in mice, rats, monkeys, sheep, and cats has helped to reveal mechanisms of pathogenesis of asthma in humans. All of these species s...
Inhaled corticosteroids modulate the (+)insert smooth muscle myosin heavy chain in the equine asthmatic airways. Overexpression of the (+)insert smooth muscle myosin heavy chain (SMMHC) isoform could contribute to airway bronchospasm by increasing the velocity of contraction. Whether the (+)insert isoform is present in the small airways and its expression is reversible in asthma are unknown. Objective: To determine the anatomical location and the expression kinetics of the (+)insert SMMHC isoform in airways of horses with heaves and to evaluate its modulation in response to disease status. Methods: We evaluated the (+)insert SMMHC isoform in the airways of horses with heaves during disease exacerbation a...
Airway wall eosinophilia is not a feature of equine heaves. 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...
Concomitant inhibition of primary equine bronchial fibroblast proliferation and differentiation by selective β2-adrenoceptor agonists and dexamethasone. 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...
Technical and physiological determinants of airway smooth muscle mass in endobronchial biopsy samples of asthmatic horses. Morphometric analyses of endobronchial biopsies are commonly performed in asthma research but little is known about the technical and physiological parameters contributing to measurement variability. We investigated factors potentially affecting biopsy size, quality, and airway smooth muscle (ASM) content in heaves, an asthma-like disease of horses. Horses with heaves in clinical exacerbation (n = 6) or remission (n = 6) from the disease and six controls were studied using a crossover design. The effect of disease status, age, bronchodilation, biopsy forceps type, and carina size on total biop...
Use of a novel one-nostril mask-spacer device to evaluate airway hyperresponsiveness (AHR) in horses after chronic administration of albuterol. Inflammatory airway disease (IAD) is very common in stabled horses. Short-acting beta agonist (SABA) drugs are often used to relieve clinical signs, although long-term exposure to these drugs may result in rebound bronchoconstriction. The purpose of this study was twofold: i) to describe the deposition of radiolabeled drugs using a novel one-nostril design mask-spacer combination with a breath-activated inhaler (BAI), and ii) to determine whether treatment for 10 d with inhaled albuterol using this device would impair the ability of albuterol to prevent bronchospasm during a histamine challeng...
Airway collagen and elastic fiber content correlates with lung function in equine heaves. 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...
Comparative study of the effects of fetal bovine serum versus horse serum on growth and differentiation of primary equine bronchial fibroblasts. 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...
Secretoglobin 1A1 and 1A1A differentially regulate neutrophil reactive oxygen species production, phagocytosis and extracellular trap formation. 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...
Environmental exposures and airway inflammation in young thoroughbred horses. Inflammatory airway disease (IAD) in horses is a widespread, performance-limiting syndrome believed to develop in response to inhaled irritants in the barn environment. Objective: To evaluate changes in bronchoalveolar lavage fluid (BALF) cytology and exposure to particulates, endotoxin, and ammonia during horses' first month in training. Methods: Forty-nine client-owned 12- to 36-month-old Thoroughbred horses entering race training. Methods: In this prospective cohort study, a convenience sample of horses was assigned to be fed hay from a net (n = 16), whereas the remaining horses were fed ha...
Real time RT-PCR analysis of inflammatory mediator expression in recurrent airway obstruction-affected horses. 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...
Apoptotic effects of tamoxifen on leukocytes from horse peripheral blood and bronchoalveolar lavage fluid. 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...
Breathing pattern and thoracoabdominal asynchrony in horses with chronic obstructive and inflammatory lung disease. 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 ...
Multiple secretoglobin 1A1 genes are differentially expressed in horses. 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...
The effect of intravenous lidocaine infusion on bronchoalveolar lavage cytology in equine recurrent airway obstruction. 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...
Neutrophils are not less sensitive than other blood leukocytes to the genomic effects of glucocorticoids. Neutrophils are generally considered less responsive to glucocorticoids compared to other inflammatory cells. The reported increase in human neutrophil survival mediated by these drugs partly supports this assertion. However, it was recently shown that dexamethasone exerts potent anti-inflammatory effects in equine peripheral blood neutrophils. Few comparative studies of glucocorticoid effects in neutrophils and other leukocytes have been reported and a relative insensitivity of neutrophils to these drugs could not be ruled out. Objective: We assessed glucocorticoid-responsiveness in equine an...
Direct and indirect exposure to horse: risk for sensitization and asthma. Most studies on the sensitization to horse allergens in populations without professional exposure have been carried out in geographical areas where the rate of horse ownership is high and horse riding is popular. Very few studies have been carried out in populations living in large urban areas. This gap in the literature probably reflects the widespread view that prevalence of horse-related allergy is low in urban populations because the latter are not regularly exposed to horses. On the contrary, we suggest that urban areas constitute a model useful to study potential modalities of exposure a...
Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model. 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...
Pulmonary intravascular macrophages as proinflammatory cells in heaves, an asthma-like equine disease. Heaves, an obstructive neutrophilic airway inflammation of horses, is triggered by dust components such as endotoxin and has similarities to human asthma. Pulmonary intravascular macrophages (PIMs) increase horses' sensitivity to endotoxin-induced lung inflammation; however, their role in an airborne pathology remains unknown. Therefore, we investigated the role of PIMs in the development of heaves in horses. Clinical and inflammatory responses were evaluated following induction of heaves by moldy hay exposure and PIM depletion with gadolinium chloride (GC). Mares (N = 9) were exposed to four ...
Detection of fluticasone propionate in horse plasma and urine following inhaled administration. Fluticasone propionate (FP) is an anti-inflammatory agent with topical and inhaled applications commonly used in the treatment of asthma in steroid-dependent individuals. The drug is used in racehorses to treat Inflammatory Airway Disease; this work was performed in order to advise on its use and detect potential misuse close to racing. Methods were developed for the extraction and analysis of FP from horse plasma and a carboxylic acid metabolite (FP-17βCOOH) from horse urine. The methods utilize ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in ...