Coughing,mucus accumulation,airway obstruction,and airway inflammation in control horses and horses affected with recurrent airway obstruction

OBJECTIVE: To investigate relationships between cough frequency and mucus accumulation, airway obstruction, and airway inflammation and to determine effects of dexamethasone on coughing and mucus score. ANIMALS: 13 horses with recurrent airway obstruction (RAO) and 6 control horses. PROCEDURE: 6 RAO-affected and 6 control horses were stabled for 3 days. Coughing was counted for 4 hours before and on each day horses were stabled. Before and on day 3 of stabling, tracheal mucus accumulation was scored, airway obstruction was assessed via maximal change in pleural pressure (deltaPpl(max)), and airway inflammation was evaluated by use of cytologic examination of bronchoalveolar lavage fluid (BALF). Effects of dexamethasone (0.1 mg/kg, IV, q 24 h for 7 days) were determined in 12 RAO-affected horses. RESULTS: To assess frequency, coughing had to be counted for 1 hour. In RAO-affected horses, stabling was associated with increases in cough frequency, mucus score, and deltaPpl(max). Control horses coughed transiently when first stabled. In RAO-affected horses, coughing was correlated with deltaPpl(max), mucus score, and airway inflammation and was a sensitive and specific indicator of deltaPpl(max) > 6 cm H2O, mucus score > 1.0, and > 100 neutrophils/microL and > 20% neutrophils in BALF Dexamethasone reduced cough frequency, mucus score, and deltaPpl(max), but BALF neutrophil count remained increased. CONCLUSIONS AND CLINICAL RELEVANCE: Because of its sporadic nature, coughing cannot be assessed accurately by counting during brief periods. In RAO-affected horses, coughing is an indicator of airway inflammation and obstruction. Corticosteroid treatment reduces cough frequency concurrently with reductions in deltaPpl(max) and mucus accumulation in RAO-affected horses.     

Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone

REASONS FOR PERFORMING STUDY: 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. OBJECTIVES: 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 0.8 ppm ozone for 2 h at rest. RESULTS: At baseline, bronchoalveolar lavage fluid (BALF) ascorbic acid concentrations were lower in RAO-affected horses than healthy controls. Ozone appeared to preferentially oxidise glutathione rather than ascorbic acid 6 h after exposure. Individual healthy and RAO-affected horses demonstrated oxidation of BALF glutathione after ozone exposure. Overall, RAO-affected horses did not demonstrate increased oxidative stress following ozone exposure, compared with healthy horses. Ozone did not induce significant airway inflammation in either group. CONCLUSIONS: RAO-affected horses in remission are not more sensitive to ozone despite a decreased pulmonary antioxidant capacity. Sensitivity to ozone appears to be independent of initial pulmonary antioxidant status. POTENTIAL RELEVANCE: Horses with high susceptibility to oxidative stress may benefit from antioxidant supplementation.     

Comparison of results for intradermal testing between clinically normal horses and horses affected with recurrent airway obstruction

OBJECTIVE: To evaluate differences in response to ID injection of histamine, phytohemagglutinin (PHA), and Aspergillus organisms between clinically normal horses and horses with recurrent airway obstruction (RAO). ANIMALS: 5 healthy adult horses and 5 adult horses with RAO. PROCEDURE: Intradermal testing (IDT) was performed on the neck with 2 positive control substances (histamine and PHA) and a mixture comprising 5 Aspergillus species. Four concentrations of each test substance plus a negative control substance were used. Equal volumes (0.1 mL) of each test substance were prepared to yield 15 syringes ([4 concentrations of each test substance plus 1 negative control substance] times 3 test substances) for each side of each horse (ie, 30 syringes/horse). Intradermal injections were administered; diameter of wheals was recorded 0.5, 4, and 24 hours after injection. RESULTS: Hypersensitive responses to ID injection of histamine were detected 0.5 hours after injection, and a delay in wheal formation after ID injection of Aspergillus mixture 24 hours after injection was detected in RAO-affected horses but was not observed in clinically normal horses. No differences were detected between the 2 groups after ID injection of PHA. CONCLUSIONS AND CLINICAL RELEVANCE: RAO-affected horses are hypersensitive to histamine, suggesting that RAO is associated with a heightened vascular response to histamine. Higher concentrations of Aspergillus mixture may be needed to detect horses that are sensitive to this group of antigens. Wheal reactions to Aspergillus may be a delayed response, suggesting that IDT results should be evaluated 0.5, 4, and 24 hours after ID injection.     

Abnormalities in lung surfactant in horses clinically affected with recurrent airway obstruction (RAO)

Background: Abnormalities in lung surfactant are well described in human respiratory diseases including asthma, but are poorly described in horses. Hypothesis: Lung surfactant is abnormal in horses with clinical signs of recurrent airway obstruction (RAO). Animals: Six healthy horses and 5 horses with RAO. Methods: Bronchoalveolar lavage fluid (BALF) was obtained from all horses by standard procedures. Cell‐free BALF was separated into crude surfactant pellets (CSP) and supernatant via ultracentrifugation. Phospholipid and protein content was analyzed from both of these fractions. Phospholipid composition of CSP was determined using high‐performance liquid chromatography with an evaporative light scatter detector. Surface tension of CSP was measured with a pulsating bubble surfactometer. Results: Compared with healthy horses, surfactant from RAO‐affected horses was characterized by significantly decreased phospholipid content in total surfactant (median; range: 23.2; 14.7–62.2 μg/mL BALF versus 172; 111–267 μg/mL BALF, P= .0062) and CSP (20.2; 6.4–48.9 μL/mL BALF versus 155; 94.4–248 μg/mL BALF, P= .0062), and a significantly lower percentage of phosphatidylglycerol (PG) (4.5; 3.6–5.6% versus 6.6; 4.1–7.6%, P= .028). Furthermore, the ratio between the percentages of phosphatidylcholine and PG was significantly higher in RAO‐affected horses than in healthy horses (20.9; 16.6: 25.9 versus 13.9; 11.8–22.8, P= .045). Conclusions and Clinical Importance: This study demonstrates that surfactant from RAO‐affected horses is abnormal. Further studies are needed to determine if these abnormalities are related to an increased tendency for bronchoconstriction and to a decreased ability to clear airway mucus in RAO‐affected horses.     

Pulmonary epithelial lining fluid and plasma ascorbic acid concentrations in horses affected by recurrent airway obstruction

OBJECTIVE: To determine the pulmonary epithelial lining fluid (ELF) concentrations and degree of oxidation of ascorbic acid in horses affected by recurrent airway obstruction (RAO) in the presence and absence of neutrophilic airway inflammation. ANIMALS: 6 RAO-affected horses and 8 healthy control horses. PROCEDURE: Nonenzymatic antioxidant concentrations were determined in RBC, plasma, and ELF samples of control horses and RAO-affected horses in the presence and absence of airway inflammation. RESULTS: ELF ascorbic acid concentration was decreased in RAO-affected horses with airway inflammation (median, 0.06 mmol/L; 25th and 75th percentiles, 0.0 and 0.4 mmol/L), compared with RAO-affected horses without airway inflammation (1.0 mmol/L; 0.7 and 1.5 mmol/L) and control horses (2.2 mmol/L; 1.4 and 2.2 mmol/L). Epithelial lining fluid ascorbic acid remained significantly lower in RAO-affected horses without airway inflammation than in control horses. Moreover, the ELF ascorbic acid redox ratio (ie, ratio of the concentrations of dehydroascorbate to total ascorbic acid) was higher in RAO-affected horses with airway inflammation (median, 0.85; 25th and 75th percentiles, 0.25 and 1.00), compared with RAO-affected horses without airway inflammation (0.04; 0.02 and 0.22). The number of neutrophils in bronchoalveolar lavage fluid was inversely related to the ELF ascorbic acid concentration (r = -0.81) and positively correlated with the ascorbic acid redox ratio (r = 0.65). CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophilic inflammation in horses affected by RAO is associated with a reduction in the ELF ascorbic acid pool. Nutritional supplementation with ascorbic acid derivatives in horses affected by RAO is an area for further investigation.     

Cardiovascular effects of acute pulmonary obstruction in horses with recurrent airway obstruction

BACKGROUND: Recurrent airway obstruction (RAO) is common in horses. Although pulmonary artery (PA) pressure increases during RAO, cardiac function in horses with RAO has received limited attention. HYPOTHESIS: The purpose of this study was to noninvasively determine the cardiovascular effects of acute pulmonary obstruction (APO) in horses with RAO and their reversibility. ANIMALS: Five geldings with RAO, inducible by exposure to moldy hay, were studied. METHODS: Pulmonary mechanics, echocardiography, serum troponin I concentrations, arterial blood gases, and hematocrit were obtained before and after 7 days of APO. Heart rate, PA diameter and flow characteristics, right and left ventricular luminal dimensions and wall thicknesses, global cardiac performance, and evidence of myocardial damage were evaluated. Pulmonary mechanics and echocardiography were reevaluated during remission. RRESULTS: Severe, transient APO did not induce chronic cor pulmonale in horses, because cardiac anatomy and function were normal between episodes. An acute episode of APO produced anatomical and functional cardiac changes in both the right and left heart (including increased PA diameter, abnormal septal motion, and decreased left ventricular diameter and estimated stroke volume), possibly because of the development of pulmonary hypertension, without apparent myocardial damage. The decrease in stroke volume was offset by the increase in heart rate. CONCLUSIONS AND CLINICAL IMPORTANCE: With APO of 7 days' duration, cardiovascular abnormalities and the functional airway changes that produce them are reversible when the offending allergens are removed.     

Efficacy of salmeterol xinafoate in horses with recurrent airway obstruction.

OBJECTIVE: To determine the onset, magnitude, and duration of bronchodilation after administration of aerosolized salmeterol xinafoate in horses with recurrent airway obstruction. DESIGN: Randomized controlled study ANIMALS: 6 horses with recurrent airway obstruction. Procedure Horses received aerosolized salmeterol (210 microg) or no treatment, using a crossover design. Salmeterol was administered, using a mask designed for aerosol delivery in horses. Subjective rating of airway obstruction (RAO), maximal change in pleural pressure (deltaPplmax), and pulmonary resistance (RL) were determined at baseline; 5, 15, and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours after administration of salmeterol and in horses that did not receive treatment. RESULTS: The deltaPpl and RL were improved 15 minutes through 6 hours after administration of salmeterol, compared with values obtained from horses receiving no treatment. The RAO was improved 15 minutes through 2 hours after administration of salmeterol. The maximal response to salmeterol was evident 30 to 60 minutes after administration and was characterized by a 59 + 19% decrease in deltaPpl and a 56 +/- 13% decrease in RL. The deltaPpl and RL were not different from baseline values 8 hours after salmeterol administration. CONCLUSIONS AND CLINICAL RELEVANCE: Duration of action of salmeterol in these horses was approximately 6 hours. Maximal bronchodilation was somewhat delayed (30 to 60 minutes), and the magnitude of response was similar to that of short-acting beta2-adrenergic agonists. Salmeterol provides moderately sustained bronchodilation in horses with recurrent airway obstruction and may be an effective drug for long-term control of this condition.     

Efficacy of oral and intravenous dexamethasone in horses with recurrent airway obstruction

REASONS FOR PERFORMING STUDY: Although the efficacy of dexamethasone for the treatment of recurrent airway obstruction (RAO) has been documented, the speed of onset of effect and duration of action are unknown, as is the efficacy of orally administered dexamethasone with or without fasting. OBJECTIVES: To document the time of onset of effect and duration of action of a dexamethasone solution i.v. or orally with and without fasting. METHODS: Protocol 1 used 8 RAO-affected horses with airway obstruction in a crossover design experiment that compared the effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary function over 4 h. Protocol 2 used 6 similar horses to compare, in a crossover design, the effects of dexamethasone i.v. (0.1 mg/kg bwt), dexamethasone per os (0.164 mg/kg bwt) with and without prior fasting, and dexamethasone per os (0.082 mg/kg) with fasting. RESULTS: Dexamethasone i.v. caused significant improvement in lung function within 2 h with a peak effect at 4-6 h. Dexamethasone per os was effective within 6 h with peak effect at 24 h at a dose of 0.164 mg/kg bwt prior to feeding. The duration of effect was, for all dexamethasone treatments, statistically significant for 30 h when compared to saline and tended to have a longer duration of effect when used orally. Dexamethasone per os at a dose of 0.164 mg/kg bwt to fed horses had mean effects comparable to dexamethasone at a dose of 0.082 mg/kg bwt per os given to fasted horses, indicating that feeding decreases bioavailability. CONCLUSIONS: Dexamethasone administered i.v. has a rapid onset of action in RAO-affected horses. Oral administration of a bioequivalent dose of the same solution to fasted horses is as effective as i.v. administration and tends to have longer duration of action. Fasting horses before oral administration of dexamethasone improves the efficacy of treatment. POTENTIAL RELEVANCE: Oral administration to fasted horses of a dexamethasone solution intended for i.v. use provides an effective treatment for RAO-affected animals.     

A region on equine chromosome 13 is linked to recurrent airway obstruction in horses

REASONS FOR STUDY: Equine recurrent airway obstruction (RAO) is probably dependent on a complex interaction of genetic and environmental factors and shares many characteristic features with human asthma. Interleukin 4 receptor a chain (IL4RA) is a candidate gene because of its role in the development of human asthma, confirmation of this association is therefore required. METHODS: The equine BAC clone containing the IL4RA gene was localised to ECA13q13 by the FISH method. Microsatellite markers in this region were investigated for possible association and linkage with RAO in 2 large Warmblood halfsib families. Based on a history of clinical signs (coughing, nasal discharge, abnormal breathing and poor performance), horses were classified in a horse owner assessed respiratory signs index (HOARSI 1-4: from healthy, mild, moderate to severe signs). Four microsatellite markers (AHT133, LEX041, VHL47, ASB037) were analysed in the offspring of Sire 1 (48 unaffected HOARSI 1 vs. 59 affected HOARSI 2-4) and Sire 2 (35 HOARSI 1 vs. 50 HOARSI 2-4), age 07 years. RESULTS: For both sires haplotypes could be established in the order AHT133-LEXO47-VHL47-ASB37. The distances in this order were estimated to be 2.9, 0.9 and 2.3 centiMorgans, respectively. Haplotype association with mild to severe clinical signs of chronic lower airway disease (HOARSI 2-4) was significant in the offspring of Sire 1 (P = 0.026) but not significant for the offspring of Sire 2 (P = 0.32). Linkage analysis showed the ECA13q13 region containing IL4RA to be linked to equine chronic lower airway disease in one family (P<0.01), but not in the second family. CONCLUSIONS: This supports a genetic background for equine RAO and indicates that IL4RA is a candidate gene with possible locus heterogeneity for this disease. POTENTIAL RELEVANCE: Identification of major genes for RAO may provide a basis for breeding and individual prevention for this important disease.     

Efficacy and safety of sound wave treatment of recurrent airway obstruction in horses

Background: One proposed nonmedical therapy for recurrent airway obstruction (RAO) in horses is a handheld acoustic device that propels sound waves from the nose down the tracheobronchial tree where it is intended to dislodge mucous and relax bronchospasm, permitting clearance of mucoid secretions. Objective: To evaluate the effectiveness and safety of this device when used as per the manufacturer's recommendations as a treatment for RAO. Animals: Nine adult horses previously diagnosed with RAO. Methods: Prospective, cross‐over clinical trial. Horses were exposed to a dusty environment until airway obstruction developed as defined by standard lung mechanics (SLM). Horses were randomly assigned to receive either acoustic therapy or a sham treatment for 4 weeks while being maintained in this environment. Horses were evaluated by clinical scores, SLM, and forced expiration regularly for 4 weeks. The opposite treatment was administered after a washout period. Results: Seven horses received the treatment; 9 received the sham. There were no changes (P > .05) in clinical score, maximal change in transpulmonary pressure (ΔP_Lmax), lung resistance (R_L), or the forced expiratory flow rate averaged over the last 75–95% of expiration (FEF_75?95%) over the study period. The device was determined to be safe, although several minor adverse effects were noted, including head tossing, coughing, and chewing during treatment. Conclusions and Clinical Importance: Treatment with this device did not improve clinical signs or lung function in horses with RAO kept in a dusty environment. Currently accepted treatments, including environmental management and medical therapy, should be recommended.     

In vitro responses of distal airways in horses with recurrent airway obstruction

Distal airway segments (ID, 3 to 4 mm; length, 5 mm) from 2 groups of horses were isolated and suspended in tissue baths filled with Krebs solution, aerated with 5% CO2 in oxygen and maintained at 37 degrees C. Responses to exogenous acetylcholine, isoproterenol, or electrical field stimulation were compared. Control horses (n = 30) had no history of recurrent airway obstruction, whereas principal horses (n = 15) had recurrent airway obstruction and were studied during an acute episode of airway obstruction. Although the distal airways contracted in response to the cumulative half-logarithmic addition of acetylcholine (10(-10) M to 10(-3) M) in both groups, bronchi obtained from principals were less sensitive to acetylcholine than were bronchi obtained from controls. Tetdrodotoxin-sensitive electrical field stimulation-induced contractions were observed in both groups of airways, but the tension achieved in principal bronchi was less than in controls. All electrical field stimulation-induced contractions were abolished by atropine, indicating that the only excitatory innervation of equine distal airway is through the parasympathetic system. To examine the effect of isoproterenol and determine inhibitory innervation, bronchi were precontracted with histamine. Electrical field stimulation did not cause relaxation of precontracted bronchi in either group, thus indicating that distal airways lack inhibitory innervation. Isoproterenol caused similar, dose-dependent relaxation in both groups.     

Lung function and airway cytologic profiles in horses with recurrent airway obstruction maintained in low-dust environments

BACKGROUND: The effects of long-term environmental management on airway obstruction and inflammation in horses with recurrent airway obstruction (RAO) are unknown. HYPOTHESIS: Horses with RAO maintained in low-dust environments have persistent airway obstruction and neutrophilic inflammation. ANIMALS: 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. METHODS: In this cross-sectional study, a clinical examination was performed, and the clinical score was calculated. Standard lung function, forced expiratory maneuvers, and the cytology of bronchoalveolar lavage fluid (BALF) were evaluated. RESULTS: The clinical scores of the RAO horses were higher than those of the non-RAO horses at time 2 (P = .018). Standard lung function data were not different between the groups at any time point. The forced expiratory flow between 75-95% of exhaled vital capacity was lower in RAO horses than in non-RAO horses at all time points (P < .02), indicating persistent peripheral airway obstruction. Cytologic evaluation of BALF revealed no difference in total nucleated cell numbers or differential cell counts between RAO and non-RAO horses at any time point. CONCLUSIONS AND CLINICAL IMPORTANCE: The peripheral airway obstruction detected in horses with RAO maintained in low-dust environments likely is due to irreversible airway remodeling but is not associated with cytologic evidence of airway inflammation.     

Daily variability of forced oscillometry parameters in horses suffering recurrent airway obstruction, a pilot study

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 all frequencies, in the morning as well as in the afternoon. X_rs showed the same significant differences for frequencies greater than 1 Hz. Overall, R_rs showed a smaller variability than X_rs. Neither outdoor temperature, nor room temperature affected R_rs. This also applied to X_rs except for the measurements at 2 Hz that were significantly (p?=?0.044) affected by outdoor temperature. Turning out these horses at paddock for day and night caused a significant lower mean R_rs that when kept at stable for all night. While R_rs showed a very weak positive frequency dependency, X_rs clearly showed a positive frequency dependance for all horses. Resonance frequency (f_res) was between 2 and 4 Hz. These studies showed that FOS generated parameters are affected by environmental and management factors and thus only after well-designed standardized procedures FOS could be a useful diagnostic tool for the diagnosis and monitoring of equine respiratory disorders.     

Tracheobronchial mucus viscoelasticity during environmental challenge in horses with recurrent airway obstruction

The goal of this study was to compare the rheological properties of mucus from horses with recurrent airway obstruction (RAO) to that from healthy controls during environmental challenge by stabling in stalls with straw as bedding and hay as feed. We determined viscoelasticity (log G* dyn/cm2, at 10 radian/s) and calculated mucociliary clearability index (MCI) and cough clearability index (CCI), which are derivative parameters of G* and the ratio of viscosity and elasticity measured at 1 and 100 radian/s, respectively. We also investigated the solids content of mucus, and cytology of bronchoalveolar lavage fluid (BALF). Samples were obtained before (0 h) and 6, 24 and 48 h after environmental challenge. The central findings were rheological changes in airway mucus, which occurred over time in RAO-affected animals, but not in controls. Mucus rheology was similar in both groups at 0 and 6 h. In RAO-affected horses, mucus viscoelasticity, as measured by log G*, increased from 2.49 +/- 0.18 dyn/cm2 (mean +/- s.e.) at 0 h to 3.05 +/- 0.13 dyn/cm2 at 24 h after environmental challenge, and was accompanied by significant decreases in MCI and CCI. Percent solids of mucus did not differ significantly between the 2 groups, nor over time. Rheological values did not correlate with BALF cytology. We conclude that viscoelastic properties of tracheal mucus samples from RAO horses in remission do not differ from those of normal horses. However, environmental challenge causes clinical signs of small airway disease and a concurrent increase in mucus viscoelasticity only in RAO horses. Therefore, we infer that unfavourable changes in mucus rheology may contribute to stasis and accumulation of mucus in RAO horses in exacerbation, but not in clinical remission.     

Comparison of efficacy and tolerability of isoflupredone and dexamethasone in the treatment of horses affected with recurrent airway obstruction ('heaves')

REASONS FOR PERFORMING STUDY: Corticosteroids are currently the most effective drugs for the control of 'heaves' in horses. However, there is limited information concerning the comparative efficacy and tolerability of the various corticosteroids when used for treatment. OBJECTIVES: To compare the therapeutic and side effects of isoflupredone acetate to those of dexamethasone. METHODS: A parallel design to compare the effects of 2 corticosteroids by evaluating lung function, serum cortisol and electrolyte concentrations, response to ACTH stimulation and haematology sequentially during a 14 day control period (no treatment), followed by 14 day treatment with either isoflupredone acetate (0.03 mg/kg i.m. s.i.d., n = 6) or dexamethasone (0.04 mg/kg i.v. s.i.d., n = 6) and 7 days of wash-out. RESULTS: Both drugs were well tolerated clinically and resulted in a significant improvement in lung function that started on Day 3 and lasted for the treatment and wash-out periods. Blood cortisol levels were significantly decreased during the treatment period in both groups of horses, but a normal response to ACTH stimulation was preserved. Serum electrolytes concentration of horses receiving dexamethasone was not affected by the treatment, but horses treated with isoflupredone demonstrated a significant decrease in serum potassium level. Both treatments induced stress changes in haematology. CONCLUSIONS AND POTENTIAL RELEVANCE: Isoflupredone is as effective as dexamethasone in the treatment of 'heaves'-affected horses but associated with hypokalaemia. Even if clinical signs of hypokalaemia were not observed, this is a side effect that deserves further investigation.     

The effect of adding oral dexamethasone to feed alterations on the airway cell inflammatory gene expression in stabled horses affected with recurrent airway obstruction

BACKGROUND: Chemokine expression in airway epithelium and bronchoalveolar lavage fluid (BALF) cells of horses with recurrent airway obstruction (RAO) is increased. HYPOTHESIS: For RAO-affected horses that are stabled and fed a pelleted ration, the addition of oral dexamethasone further improves pulmonary function and reduces inflammatory gene expression in pulmonary cells. ANIMALS: Twelve RAO-affected horses. METHODS: In a randomized cross-over experiment, the effect of feeding pellets in lieu of hay to stabled, RAO-affected horses was compared with the effect of feeding pellets and administering a 21-day decreasing dose regimen of oral dexamethasone on the expression (by kinetic polymerase chain reaction) of interleukin-8 (IL-8), chemokine (C-X-C motif) ligand 2 (CXCL2), IL-1beta, IL-6, and beta-actin in the BALF cells and of IL-8, CXCL2, 2 IL-1 receptor (IL-1R2), Toll-like receptor 4 (TLR4), and glyceraldehyde 3-phosphate dehydrogenase in the bronchial epithelium 2 days after the final dose. RESULTS: Both treatments reduced airway neutrophilia and breathing efforts but the addition of dexamethasone was associated with fewer treatment failures. Compared with feed changes alone, dexamethasone administration further reduced the expression of IL-8, CXCL2, and IL-1beta in the BALF cells 3.3-, 2.5-, and 4.7-fold, respectively. In the airway epithelium, both treatments were equally efficacious in reducing the expression of IL-8 and CXCL2 expression relative to pretreatment values, but either treatment failed to alter the expression of IL-1R2 and TLR4. CONCLUSIONS AND CLINICAL IMPORTANCE: For a rapid and consistent improvement in pulmonary function and a reduction in inflammatory gene expression of the BALF cells, a decreasing dose of oral dexamethasone in combination with feed alterations is more efficacious for horses that must remain stabled.     

The anti-inflammatory effects of IV administered clenbuterol in horses with recurrent airway obstruction

Cyclic AMP elevating agents have been shown to exhibit anti-inflammatory properties in addition to functions such as bronchodilation. The aim of this study was to investigate this dual action of clenbuterol (CB; Ventipulmin) on horses affected with recurrent airway obstruction (RAO). Seven RAO susceptible horses received inhalation challenges with aerosolised lipopolysaccharide (LPS), hay dust suspension (HDS) and Aspergillus fumigatus antigen (AF) with and without prior treatment with intravenous CB. Data showed that CB exerted significant beneficial effects on lung function, total cell count (TCC) and bronchoalveolar lavage neutrophil influx. In addition, CB significantly decreased the expression of several pro-inflammatory cytokines and chemokines in the alveolar macrophages of RAO-susceptible horses after challenge with LPS and HDS, and increased the expression of interleukin-6, known to act as a pro-and anti-inflammatory cytokine, following different challenges. This anti-inflammatory activity of CB is of additive value to its currently recognised use in equine RAO.