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Topic:Airway Disease
Airway disease in horses is defined as a respiratory condition marked by inflammation and narrowing of the lower airways, leading to symptoms like coughing, increased mucus production, and reduced performance. This condition, which includes forms such as inflammatory airway disease (IAD) and recurrent airway obstruction (RAO), can significantly impact a horse’s respiratory efficiency and overall health.
This page compiles peer-reviewed research studies and clinical insights that explore the pathophysiology, diagnostic techniques, and effective treatment protocols to manage and improve equine respiratory health.
Antimicrobial drug concentrations and sampling techniques in the equine lung. The distribution of antimicrobial drugs in the equine lung is important in designing optimal dosage regimens for the treatment of lower airway infections. Several studies in horses and other species have shown that the pharmacokinetics of a drug in the lung cannot necessarily be predicted by its behaviour in plasma, and influencing factors include the class of drug, the animal species and the chosen sampling technique. This review provides a description of the target site for bacterial lower airway infections and describes the penetration of antibiotics into lung matrices. It also offers an ov...
Effect of prolonged administration of clenbuterol on airway reactivity and sweating in horses with inflammatory airway disease. To determine whether prolonged administration of clenbuterol results in tachyphylaxis, specifically regarding its bronchoprotective properties and effect on sweating in horses. Methods: 8 Thoroughbreds with inflammatory airway disease. Methods: In a crossover design, horses received clenbuterol (0.8 μg/kg, p.o., q 12 h) or placebo for 21 days, with a washout period of ≥ 30 days between the 2 treatments. Airway reactivity was evaluated by use of flowmetric plethysmography and histamine broncho-provocation before (day 0; baseline) and every 7 days after the start of treatment. Sweat function ...
Increased adenosine concentration in bronchoalveolar lavage fluid of horses with lower airway inflammation. Several reports have suggested a role for adenosine in the pathogenesis of chronic airway conditions and this has led to new therapeutic strategies to limit airway inflammation. In this study, detectable levels of adenosine in bronchoalveolar lavage (BAL) samples from 11 horses with non-infectious lower-airway inflammation and 14 healthy controls are reported, with significantly higher values in horses with airway inflammation. Although these increased levels did not correlate with changes in neutrophil percentage in BAL, a positive association between adenosine levels and signs of lower airwa...
Comparison of cytokine mRNA expression in the bronchoalveolar lavage fluid of horses with inflammatory airway disease and bronchoalveolar lavage mastocytosis or neutrophilia using REST software analysis. The pathophysiology of inflammatory airway disease (IAD) is unknown, but in some cases involves the accumulation of mast cells, neutrophils, or both in the bronchoalveolar lavage fluid (BALF). The objective of this study was to characterize cytokine gene expression in the BALF cells of horses with IAD, including a comparison of cytokine gene expression between IAD horses with increased BALF mast cells (IAD-Mast) or neutrophils (IAD-Neutro). Methods: The mRNA expression of IL-4, IFN-γ, IL-17, IL-8, IL-1β, IL-5, IL-6, IL-10, IL-12p35, and eotaxin-2 was studied by quantitative polymerase chain ...
Dynamic respiratory videoendoscopy in ridden sport horses: effect of head flexion, riding and airway inflammation in 129 cases. Dynamic upper airway obstruction (UAO) is a cause of respiratory noise and sometimes poor performance in sport horses. Riding, head flexion and airway inflammation may impact upper respiratory tract stability during exercise. Objective: To evaluate upper airway mechanical behaviour in ridden sport horses using overground endoscopy and the effect of head flexion, rider intervention and underlying airway inflammation on the pharynx and larynx. Methods: Resting and exercising videoendoscopic recordings during ridden exercise were obtained in 129 sport horses referred mainly for respiratory noise,...
Pulmonary edema at recovery after colic operation with in-situ nasogastric tube in a horse. After an uneventful general anesthesia, in a horse negative pressure pulmonary edema developed due to acute upper airway obstruction during the anesthetic recovery phase after colic surgery. No pathologic alteration of respiration was observed until the horse stood up and began suffocating. The horse had recovered with the nasogastric tube in situ. This, together with the postmortem diagnosis of laryngeal hemiplegia resulted in impairment of airflow through the larynx and development of pulmonary edema. Our objective is to alert clinicians about the possible hazard of recovery with an in-situ ...
Heaves, an asthma-like disease of horses. 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 ...
Spi2 gene polymorphism is not associated with recurrent airway obstruction and inflammatory airway disease in thoroughbred horses. The aim was to detect the presence of polymorphisms at exons 1, 2, 3 and 4 of the Spi2 gene, and evaluate a possible association between them and recurrent airway obstruction (RAO) or inflammatory airway disease (IAD) in thoroughbred horses, through single-strand conformational-polymorphism (SSCP) screening. Although polymorphism was not detected in exons 1, 2 and 3, three alleles and six genotypes were identified in exon 4. The frequencies of allele A (0.6388) and genotype AA (0.3888) were higher in horses affected by RAO, although no association was found between polymorphism and horses with...
Serum concentration of surfactant protein D in horses with lower airway inflammation. Surfactant protein D (SP-D), mainly synthesised by alveolar type II cells and nonciliated bronchiolar cells, is one important component of innate pulmonary immunity. In man, circulating concentrations of SP-D are routinely used as biomarkers for pulmonary injury. To date, serum SP-D levels have only been investigated in horses in an experimental model of bacterial airway infection. Objective: To compare serum SP-D concentrations at rest and after exercise in horses with and without inflammatory airway disease (IAD). Methods: Venous blood samples were collected from 42 Standardbred racehorses a...
Epiglottic abnormalities in mature nonracehorses: 23 cases (1990-2009). To identify history, clinical signs, endoscopic findings, treatment, and outcome of mature (> 8 years old) nonracehorses with epiglottic abnormalities. Methods: Retrospective case series. Methods: 23 horses with an epiglottic abnormality. Methods: Medical records of horses examined between 1990 and 2009 because of an epiglottic abnormality were reviewed to obtain information on signalment, history, clinical signs, clinical examination findings, upper airway endoscopic findings, diagnosis, surgical procedure, clinical management, postoperative care, and outcome. Results: Mean ± SD age was 1...
Evaluation of a risk-screening questionnaire to detect equine lung inflammation: results of a large field study. The diagnosis of equine recurrent airway obstruction (RAO) and inflammatory airway disease (IAD) is based on clinical signs and increased inflammatory cell percentages in the bronchoalveolar lavage (BAL) fluid. Since a BAL is an invasive procedure, a risk-screening questionnaire (RSQ) would be a valuable screening tool for lung inflammation. Objective: To evaluate the accuracy of a RSQ to detect lower airway inflammation (LAI) in a large population of horses. Methods: A standardised BAL was performed in the field on 167 horses in Alberta, Canada. Horses were separated into 3 categories: 1) BAL...
Increased apoptosis of CD4 and CD8 T lymphocytes in the airways of horses with recurrent airway obstruction. Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition similar to human asthma caused by exposure of susceptible horses to poorly ventilated stable environments. The disease is characterized by neutrophilic airway inflammation, mucus hypersecretion and reversible bronchoconstriction. This inflammatory process is mediated by several factors, including antibodies, cytokines, resident cells of the airway and inflammatory cellular components that arrive in the respiratory tract. An increasing body of evidence has lent support to the concept that a dysregulatio...
Descriptive results from a longitudinal study of airway inflammation in British National Hunt racehorses. Rates of airway inflammation in young racehorses decrease with time but it is not clear whether this is associated with increasing age or time exposed to the training environment. The structure of the British National Hunt (NH) population allowed closer examination of this relationship. Objective: To compare rates of inflammatory airway disease diagnosed by tracheal sampling (trIAD), and its components, in NH racehorses by age and training history and with published rates in young racehorses. Methods: A prospective, longitudinal study was conducted on 5 NH yards over 2 years. Period sample pre...
Enhanced IL-6 transcriptional response to adenosine receptor ligands in horses with lower airway inflammation. Accumulation of extracellular adenosine has been closely associated with human asthmatic responses. However, the relevance of adenosine signalling in equine airways has not previously been investigated. Objective: To determine the expression of adenosine receptors (AR) in bronchoalveolar lavage (BAL) cells and assess the reactivity of these cells to AR ligands ex vivo, employing IL-6 as readout of adenosinergic inflammatory signalling. Methods: Eight horses with varying degrees of lower airway inflammation and 10 healthy controls were analysed. Expression of AR-subtypes in each BAL sample was ...
Comparative efficacy of inhaled albuterol between two hand-held delivery devices in horses with recurrent airway obstruction. Studies investigating the clinical efficacy of albuterol administered with the same propellant and commercially available delivery devices in horses with recurrent airway obstruction (RAO) are not currently available. Objective: To determine the efficacy of aerosolised albuterol administered to horses with RAO by means of 2 commercially available, hand-held delivery devices. Methods: Ten horses with RAO were kept in a dusty environment and fed mouldy hay to induce airway obstruction. Lung mechanics were measured before and after the procedure. ΔP(max) was measured 5 min after administration o...
Evaluation of suitable reference genes for gene expression studies in bronchoalveolar lavage cells from horses with inflammatory airway disease. The stability of reference genes has a tremendous effect on the results of relative quantification of genes expression by quantitative polymerase chain reaction. Equine Inflammatory Airway Disease (IAD) is a common condition often treated with corticosteroids. The diagnosis of IAD is based on clinical signs and bronchoalveolar lavage (BAL) fluid cytology. The aim of this study was to identify reference genes with the most stable mRNA expression in the BAL cells of horses with IAD irrespective of corticosteroids treatment. Results: The expression stability of seven candidate reference genes (B2...
Effect of antigenic exposure on airway smooth muscle remodeling in an equine model of chronic asthma. 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...
Pulmonary function measurements immediately after exercise are correlated with neutrophil percentage in tracheal aspirates in horses with poor racing performance. Inflammatory airway disease (IAD) is common in racehorses, and is a cause of wastage in the industry. IAD has been diagnosed by measurement of percent neutrophils (N%) in tracheal aspirates (TA). The aim of this study was to investigate whether spirometric indices of pulmonary function were correlated with N% in TAs. Limits to breathing were measured by analyses of relationships between relative times and relative respiratory gas flows during inspiration and expiration in individual breaths recorded after exercise. Horses with higher N% had significantly lower relative gas flows at the same re...
Immunohistochemical identification of collagen in the equine lung. Recurrent airway obstruction (RAO) in the horse is a disease characterized by reversible bronchoconstriction and by mucus and neutrophil accumulation in the airways. It has been hypothesized that in horses with RAO, remodeling changes occur that are similar to those described in humans with asthma. Although collagen fibrils are present surrounding normal airways, they are a prominent feature of airway remodeling in human asthma with evidence of enhanced collagen III and I fibril deposition. An immunolabeling method was developed to identify collagen I and III in equine lung and to describe the...
Evaluation of MUC5AC expression and upregulation in airway epithelial cells of horses. To isolate and culture primary equine airway epithelial cells in vitro and elucidate the major cytokines involved in expression of the gel-forming mucin gene MUC5AC in horses. Methods: 12 tracheas obtained within 5 hours after euthanasia from horses free from respiratory tract disease. Methods: Tracheal rings were digested overnight in 0.2% protease, and dissociated airway epithelial cells were grown in a serum-free defined medium at an air-liquid interface until confluence was achieved. Differentiated airway epithelial cells were treated with a panel of recombinant equine cytokines followed b...
Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses. To evaluate experimental induction of recurrent airway obstruction (RAO) with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses. Methods: 7 horses with and 3 horses without a history of RAO. Methods: RAO-susceptible horses ranged in age from 17 to approximately 30 years, and control horses ranged in age from 7 to approximately 15 years. Pure mold cultures were derived from repeated culture of hay and identified via gene amplification and sequencing. Pulmonary function testing and bronchoalveolar lavage were performed before and after nebulization with a suspension of...
Pharmacological studies of bronchial constriction inhibited by parasympatholytics and cilomilast using equine precision-cut lung slices. Equine precision cut lung slices (PCLS) were used to evaluate the ability of several pharmacologic compounds, parasympatholytics atropine, ipratropium, tiotropium and phosphodiesterase (PDE) 4-inhibitor cilomilast, to inhibit methacholine (MCh) induced bronchial constriction. The study war performed using vital lung samples from 20 horses, harvested immediately after euthanasia and lung examination.Tissue samples from the cranial, caudal and accessory lobe were taken for histological examination. Viability in PCLS of 250 +/- 20 microm was confirmed by observation of cilia movement and bronchia...
Stabling causes a significant increase in the pH of the equine airway. Regulation of pH homeostasis in the equine lung is poorly understood. Measurement of exhaled breath condensate (EBC) pH provided a simple, highly repeatable and noninvasive method for the longitudinal investigation of changes in airway pH in response to environmental changes. Stabling of horses was found to lead to a small (approximately 100-200 parts/billion) but significant (P < 0.001) increase in ambient ammonia concentration when compared to pasture. This increase in exposure to ambient ammonia concentration was associated with significant (P = 0.002) increases in EBC pH and exhaled amm...
Equine bronchial epithelial cells differentiate into ciliated and mucus producing cells in vitro. We describe a method for creating differentiated equine bronchial epithelial cell cultures that can be used for in vitro studies including airway disease mechanisms and pathogen-host interactions. Our method is based on the culturing of human tracheobronchial epithelial cells at an air-liquid interface (ALI) in specific serum-free, hormone-supplemented medium. Bronchial epithelial cells are isolated and grown on T-Clear® insert membranes. Within 2 to 3 wk, cells differentiate into ciliated and mucus producing cells as demonstrated by confocal and electron microscopy. Furthermore, the demonstr...
Association of Stenotrophomonas maltophilia infection with lower airway disease in the horse: a retrospective case series. Stenotrophomonas maltophilia is being reported with increasing frequency as a human nosocomial pathogen, especially among immuno-compromised patients. To the authors' knowledge, this pathogen has not previously been associated with lower airway disease in the horse. In this paper the clinical findings, laboratory diagnosis and response to treatment of seven cases of respiratory infection with S. maltophilia in horses, presented at three equine referral hospitals in Denmark in 2007, are described. In all cases there was a clinical history of chronic coughing and abundant mucopurulent exudate wa...
Reproducibility of airway responsiveness in horses using flowmetric plethysmography and histamine bronchoprovocation. Inflammatory airway disease has a high prevalence in horses, but is often a diagnostic challenge. Flowmetric plethysmography and histamine bronchoprovocation (FP/HBP) is a simple and effective tool for diagnosis, but reproducibility of these measurements made over time has not been established. Objective: We hypothesize that the measurement of airway responsiveness in horses using FP/HBP is consistent over both short and long periods of time. Methods: Twenty-nine healthy adult horses from 2 university herds. Methods: In this prospective experimental study, airway responsiveness was determined ...
Expression of toll-like receptor 2 mRNA in bronchial epithelial cells is not induced in RAO-affected horses. Airway inflammation in recurrent airway obstruction (RAO) is triggered by housing affected horses in stables.It has been suggested that RAO is an allergic condition, but innate immune mechanisms are also involved. Fungal products activate innate immune mechanisms through toll-like receptor 2 (TLR2). In human airway epithelium, TLR2 activation leads to interleukin (IL)-8 production. This pathway is negatively regulated by the zinc finger protein A20. This study was performed to enhance understanding of innate immune mechanisms in RAO. Objective: TLR2 and IL-8 mRNA are elevated in RAO during sta...
Segment-dependent activation of muscarinic acetylcholine receptor-mediated [35S]Guanosine-5′-O-(gamma-thiotriphosphate) binding in airway tissue membranes. Muscarinic acetylcholine receptor (mAChR)-mediated guanine nucleotide-binding regulatory protein (G protein) activation and the functional interaction between receptors and the respective G proteins were investigated using an agonist-induced [(35)S]guanosine-5'-O-(gamma-thiotriphosphate) ([(35)S]GTPgammaS)-binding approach in membranes of 3 native equine airway segments (trachea, bronchus and lung), which differ tremendously in mAChR density and subtype distribution; especially subtypes that couple negatively to adenylyl cyclase through G(i/0) proteins, i.e. M(2) receptors. The assay was initi...
Implications of different degrees of arytenoid cartilage abduction on equine upper airway characteristics. The necessary degree of arytenoid cartilage abduction (ACA) to restore airway patency at maximal exercise has not been determined. Objective: Use computational fluid dynamics modelling to measure the effects of different degrees of ACA on upper airway characteristics of horses during exercise. Objective: Maximal ACA by laryngoplasty is necessary to restore normal peak airflow and pressure in Thoroughbred racehorses with laryngeal hemiplegia. Methods: The upper airway was modeled with the left arytenoid in 3 different positions: maximal abduction; 88% cross-sectional area of the rima glottis; a...
Effects of a MAPK p38 inhibitor on lung function and airway inflammation in equine recurrent airway obstruction. It has been suggested that many of the beneficial effects of corticosteroids are mediated through mitogen-activated protein kinase (MAPK) p38 inhibition. Objective: To investigate the efficacy of the MAPK p38 inhibitor compound MRL-EQ1 to either prevent (Phase 1) or treat (Phase 2) recurrent airway obstruction (RAO) in horses. Methods: MRL-EQ1 was administered i.v. at a dosage of 0.75-1.5 mg/kg bwt q. 12 h. In Phase 1, susceptible horses in clinical remission were divided into 2 groups (n = 5/group), based on historical values of respiratory mechanics. All horses were entered in the study in p...
