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1.
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.  相似文献   

2.
OBJECTIVE: To determine the dose of aerosolized albuterol sulfate required to cause bronchodilation in horses with recurrent airway obstruction (RAO) and duration of this effect. ANIMALS: 19 horses with RAO (10 in experiment 1; 9 in experiment 2). PROCEDURE: Horses were moved from pasture to stables, and airway obstruction was induced. Pulmonary function was measured in 10 horses before and 5, 10, and 30 minutes after administration of vehicle or 120, 240, 360, or 720 microg of the drug. Nine horses received vehicle or 360 or 720 microg of albuterol, and pulmonary function was measured at baseline and 5 minutes and 1, 2, 3, 4, 5, 6, and 7 hours later. Horses were evaluated for adverse drug effects. RESULTS: 360 microg of albuterol was required to cause significant bronchodilatation; 720 microg did not enhance bronchodilatation or increase duration of action. Depending on which pulmonary function parameter was evaluated, bronchodilatation achieved by use of albuterol lasted between 30 minutes and 1 hour. Because there was a significant vehicle effect, the combined effect of vehicle and drug lasted up to 3 hours. Adverse effects were not observed. CONCLUSIONS: Aerosolized albuterol, 360 or 720 microg, is a safe and effective bronchodilator in horses with RAO. Onset of action is rapid (5 minutes), and effects last from 30 minutes to 3 hours. CLINICAL RELEVANCE: Aerosolized albuterol is useful for treatment of bronchospasm in horses with RAO.  相似文献   

3.
OBJECTIVE: To evaluate effects of sedation on stability of resistance of the respiratory system (RRS) and measures of resting energy expenditure (REE) by use of open-flow indirect calorimetry (IC) and treatment with aerosolized albuterol on REE in horses with recurrent airway obstruction (RAO). ANIMALS: 9 clinically normal horses and 8 horses with RAO. PROCEDURE: In phase 1, RRS was measured by using forced oscillometry (FOT) in 5 clinically normal horses before and after sedation with xylazine. In phase 2, REE was measured in 4 clinically normal horses between 20 and 25 minutes and again 35 to 40 minutes after sedation with xylazine. In phase 3, IC was performed between 20 and 25 minutes and FOT was performed between 30 and 35 minutes after xylazine administration in 8 horses with RAO; after administration of 450 microg of albuterol, IC and FOT were repeated. RESULTS: In phase 1, RRS values were significantly lower 5 and 10 minutes after sedation. In phase 2, diminishing sedation did not significantly affect REE. In phase 3, there was a significant decrease in mean RRS (1.15 +/- 0.25 vs 0.84 +/- 0.14 cm H20/L/s) and REE (30.68 +/- 17.89 vs 27.46 = 16.54 kcal/kg/d) after albuterol administration. CONCLUSIONS AND CLINICAL RELEVANCE: FOT and IC are useful in obtaining repeatable measurements of RRS and REE, respectively, in sedated horses. Concurrent bronchodilation and decreased REE after albuterol administration suggest that increased work of breathing as a result of airway obstruction may contribute to increased energy demands in horses with RAO.  相似文献   

4.
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.  相似文献   

5.
Reasons for performing study: 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. Hypothesis: TLR2 and IL‐8 mRNA are elevated in RAO during stabling compared with controls. A20 mRNA is negatively associated with the numbers of airway inflammatory cells. Objectives: To determine TLR 2 , IL‐8 and A20 mRNA expression in lungs of stabled and pastured RAO‐affected and control horses. Methods: Airway obstruction and inflammatory cell counts in bronchoalveolar lavage were measured, and TLR 2 , IL‐8 and A20 mRNA expression quantified by qRT‐PCR in 6 RAO‐affected and 6 control horses, during and after exposure to hay and straw. Results: Airway obstruction and neutrophils were increased in RAO‐affected horses during stabling. While stabling increased IL‐ 8 , TLR2 and A20 mRNA were unaffected. TLR2 and A20 were significantly correlated (r = 0.83) and A20 mRNA was negatively associated with inflammatory cells. Potential relevance: Stabling does not lead to an increase in TLR2 expression. Other molecules or processes in the TLR2 cascade might be important in fungal‐induced airway inflammation. Equine epithelial‐derived A20 may be involved in modulation of airway inflammation.  相似文献   

6.
Reasons for performing study: Airway mucus accumulation is associated with indoor irritant and allergen exposure in horses with recurrent airway obstruction (RAO). Epidermal growth factor receptor (EGFR) and a chloride channel (calcium activated, family member 1; CLCA1) are key signalling molecules involved in mucin gene expression. Objectives: We hypothesised that exposure to irritants and aeroallergens would lead to increased expression of the mucin gene eqMUC5AC and increased stored mucosubstance in the airways of RAO‐affected horses, associated with increased neutrophils and CLCA1 and EGFR mRNA levels. Methods: We performed quantitative RT‐PCR of eqMUC5AC, CLCA1 and EGFR; volume density measurements of intraepithelial mucosubstances; and cytological differentiation of intraluminal inflammatory cells in small cartilaginous airways from cranial left and right and caudal left and right lung lobes of 5 clinically healthy and 5 RAO‐affected horses that had been exposed to indoor stable environment for 5 days before euthanasia. Results: Neutrophils were increased in RAO‐affected horses compared to clinically healthy controls. EqMUC5AC mRNA levels were positively correlated with both CLCA1 and EGFR mRNA levels in RAO‐affected horses but only with CLCA1 in controls. The relationship between eqMUC5AC and CLCA1 differed in the 2 groups of horses with RAO‐affected animals overexpressing CLCA1 in relation to eqMUC5AC. Conclusions: These data implicate CLCA1 as a signalling molecule in the expression of eqMUC5AC in horses but also suggest differential regulation by CLCA1 and EGFR between horses with RAO and those with milder degrees of airway inflammation.  相似文献   

7.
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 (ΔPLmax), lung resistance (RL), or the forced expiratory flow rate averaged over the last 75–95% of expiration (FEF75?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.  相似文献   

8.
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.  相似文献   

9.
β-Agonists have been shown to display anti-inflammatory properties in several experimental models. The aim of this study was to investigate the anti-inflammatory properties of clenbuterol (CB), administered either intravenously or by aerosol, in comparison with fluticasone propionate (FP) in recurrent airway obstruction (RAO)-susceptible horses. Eight horses, of which five were known to be susceptible to RAO, underwent an inhalation challenge with Aspergillus fumigatus (AF) antigen and were treated with CB intravenously, CB by aerosol, or FP by aerosol. Twenty-four hours after the challenge, bronchoalveolar lavage was performed, the total and differential cell counts were assessed, and cytokines were measured in isolated alveolar macrophages. After challenge with AF, RAO-susceptible horses showed an increase in total cell count, based on an increase in macrophages and lymphocytes, which was inhibited by treatment with intravenous CB, aerosolized CB and aerosolized FP. Neutrophil ratios were decreased when treated with aerosolized CB and FP. Expression of interleukin (IL)-1β and IL −8 was significantly increased after AF challenge .Interleukin −1β was significantly decreased following treatment with intravenous CB, aerosolized CB and aerosolized FP, whereas only FP decreased the expression of IL-8. These data suggest that the anti-inflammatory property of CB provide new opportunities in the therapeutic intervention of early inflammation in RAO.  相似文献   

10.
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.  相似文献   

11.
In horses, Recurrent Airway Obstruction (RAO) is an allergic disease that involves IgE mediated Type I Hypersensitivity responses. The development of this type of allergy involves a series of events that begins with reaginic antibodies, mainly IgE and some IgG subclasses. These reaginic antibodies bind with high affinity, via the Fc portion, to FcεRI receptors on the membrane of mast cells and basophils. Once bound, environmental allergens cross-link the antibodies, which results in mast cell degranulation leading to the production of histamine and other chemical mediators that act together to induce airway inflammation. RAO-affected horses present with coughing, respiratory distress, airway obstruction and poor performance. The aspect of the RAO has been extensively studied, yet the precise sequence of events is still not well understood. Therefore, this study proposes a bioassay for reaginic antibody detection from horse serum of RAO-affected individuals, in order to determine the etiology of disease, which mediate immediate type reactions. The technique involves measuring in vitro calcium mobilization in RBL-2H3 cells following incubation with horse serum from affected or unaffected horses and one of the RAO antigens (Aspergillus fumigatus). The results presented here demonstrate that 30% of RAO-affected horses react positively in this in vitro bioassay, whereas unaffected horses do not. This bioassay may facilitate further research on RAO and other allergic diseases in horses.  相似文献   

12.
OBJECTIVE: To determine the effect of a commercially available nasal strip on airway mechanics in exercising horses. ANIMALS: 6 horses (5 Standardbreds and 1 Thoroughbred). PROCEDURE: Horses exercised on a treadmill at speeds corresponding to 100 and 120% of maximal heart rate with and without application of a commercially available nasal strip. Concurrently, tracheal pressures, airflow, and heart rate were measured. Peak inspiratory and expiratory tracheal pressures, airflow, respiratory frequency, and tidal volume were recorded. Inspiratory and expiratory airway resistances were calculated by dividing peak pressures by peak flows. Endoscopic examination of the narrowest point of the nasal cavity (ie, nasal valve) was performed in 1 resting horse before, during, and after application of a nasal strip. RESULTS: During exercise on a treadmill, peak tracheal inspiratory pressure and inspiratory airway resistance were significantly less when nasal strips were applied to horses exercising at speeds corresponding to 100 and 120% of maximal heart rate. Application of the nasal strip pulled the dorsal conchal fold laterally, expanding the dorsal meatus. CONCLUSIONS AND CLINICAL RELEVANCE: The commercially available nasal strip tented the skin over the nasal valve and dilated that section of the nasal passage, resulting in decreased airway resistance during inspiration. The nasal strip probably decreases the amount of work required for respiratory muscles in horses during intense exercise and may reduce the energy required for breathing in these horses.  相似文献   

13.
Background: Efficacy of inhaled fluticasone propionate (FP) for management of recurrent airway obstruction (RAO) has only been evaluated after several weeks' treatment.
Objectives: To compare efficacy of (1) 3-day treatments with FP to dexamethasone (DEX) for management of RAO; and (2) FP and DEX to no treatment in prevention of acute RAO exacerbations.
Animals: Nine RAO affected horses.
Methods: Crossover studies in RAO-affected horses compared (a) 3-day treatment of RAO exacerbation with FP (3 and 6 mg q12h) and DEX (0.1 mg/kg q24h) and (b) FP (6 mg q12h) and DEX (0.1 mg/kg q24h) to no treatment for prevention of acute exacerbations of RAO. Treatment efficacy and unwanted effects were judged from maximal change in pleural pressure (ΔPplmax), serum cortisol (COR), bronchoalveolar lavage (BAL) cytology, and subjective scores for respiratory distress and lameness.
Results: In treatment trial, DEX and FP (6 mg) significantly decreased ΔPplmax by 48 and 72 hours, respectively; FP (3 mg) had no significant effect. DEX decreased COR more than did FP. In prevention trial, both DEX and FP (6 mg) prevented the increase in ΔPplmax that occurred in untreated horses. Both treatments decreased COR to the same degree. FP and DEX had no effects on bronchoalveolar lavage fluid (BALF) cytology and there was no evidence of laminitis.
Conclusions and Clinical Importance: FP (6 mg q12h) is as effective as DEX for prevention of acute exacerbations of RAO and lower doses should be evaluated. High-dose FP is not as effective as DEX for treatment of RAO exacerbations.  相似文献   

14.
OBJECTIVE: To identify risk factors for recurrent airway obstruction (RAO) among horses examined at veterinary teaching hospitals in North America. DESIGN: Retrospective case-control study. ANIMALS: 1,444 horses with RAO and 1,444 control horses examined for other reasons. PROCEDURE: The Veterinary Medical Database was searched for records of horses in which RAO was diagnosed. A control group was identified by randomly selecting a horse with a diagnosis other than RAO that matched the institution and year of admission for each of the horses with RAO. Information obtained included hospital, admission year and month, age, sex, breed, and discharge status. The association between risk factors and diagnosis of RAO was estimated with logistic regression models. RESULTS: The risk of RAO increased significantly with age, with horses > or = 7 years old being 6 to 7 times as likely to have RAO as were horses < or = 4 years old. Thoroughbreds were 3 times as likely to have RAO as were ponies. Horses were 1.6 and 1.5 times as likely to be examined because of RAO during winter and spring, respectively, than they were during summer. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that RAO was more likely to be diagnosed in females, horses > or = 4 years old, and Thoroughbreds and that RAO has a seasonal distribution.  相似文献   

15.
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 challenge test. The percentage of radio-aerosol deposited in the total lung was 12.39% ± 5.05%. All study horses demonstrated airway hyperresponsiveness (AHR) before enrollment in the study [mean provocative concentration eliciting 35% increase in delta flow (PC35) < 6 mg/mL histamine]. There was no significant difference in airway hyperresponsiveness to post-albuterol histamine challenge before or after treatment with albuterol. A 10-d treatment with placebo, however, caused a significant increase in airway hyperresponsiveness in all horses (P < 0.001). The results of this study show that the novel mask-spacer device was effective in delivering radiolabeled aerosolized drug to the lung and that delivery of a SABA for 10 d using this device did not result in increased airway hyperresponsiveness.  相似文献   

16.
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.  相似文献   

17.
OBJECTIVE: To determine whether pulmonary distribution of aerosolized technetium Tc 99m pentetate is improved after inhalation of a single dose of albuterol sulfate in horses susceptible to recurrent airway obstruction (heaves). ANIMALS: 6 horses with heaves and 4 horses with normal respiratory tract function. PROCEDURE: Images were obtained during ventilation of horses at baseline (maximal change in pleural pressure during tidal breathing [deltaPpImax] >15 cm H2O) and after aerosolized albuterol sulfate (360 microg) administration, with a 24-hour washout period between experiments. The deltaPpImax was determined prior to the baseline scan, prior to albuterol sulfate administration, and 5 minutes after albuterol sulfate administration. Images were assessed by visual inspection (semi-quantitative scoring system) and histogram analysis. RESULTS: Images obtained from horses with heaves had nonuniform pulmonary distribution of radionuclide characterized by poor penetration in peripheral lung fields and excess deposition in large airways. Histogram analysis of images of the caudal portions of the lungs revealed nonuniform radionuclide deposition in horses with heaves and uniform radionuclide deposition in control horses. CONCLUSION: Administration of a single dose of aerosolized albuterol sulfate improved pulmonary distribution of aerosolized radiolabeled pentetate suspension in horses with heaves but did not alter pulmonary distribution in clinically normal horses. CLINICAL RELEVANCE: Precedent bronchodilator administration may improve pulmonary distribution of aerosolized, surface-active anti-inflammatory preparations.  相似文献   

18.
Reasons for performing study: The horse owner assessed respiratory signs index (HOARSI‐1–4, healthy, mildly, moderately and severely affected, respectively) is based on owner‐reported clinical history and has been used for the investigation of recurrent airway obstruction (RAO) genetics utilising large sample sizes. Reliable phenotype identification is of paramount importance in genetic studies. Owner reports of respiratory signs have shown good repeatability, but the agreement of HOARSI with an in‐depth examination of the lower respiratory tract has not been investigated. Objectives: To determine the correlation of HOARSI grades 3/4 with the characteristics of RAO and of HOARSI‐2 with the characteristics of inflammatory airway disease. Further, to test whether there are phenotypic differences in the manifestation of lung disease between families. Methods: Seventy‐one direct offspring of 2 RAO‐affected Warmblood stallions (33 from the first family, 38 from the second) were graded as HOARSI‐1–4 and underwent a clinical examination of the respiratory system, arterial blood gas analysis, endoscopic mucus scoring, cytology of tracheobronchial secretion (TBS) and bronchoalveolar lavage fluid (BALF), and clinical assessment of airway reactivity to methacholine chloride. Results: HOARSI‐3/4 animals in clinical exacerbation showed signs consistent with RAO: coughing, nasal discharge, abnormal lung sounds and breathing pattern as well as increased numbers of neutrophils in TBS and BALF, excessive mucus accumulation and airway hyper‐responsiveness to methacholine. HOARSI‐3/4 horses in remission only had increased amounts of tracheal mucus and TBS neutrophil percentages. Clinical phenotypes were not significantly different between the 2 families. Conclusions and clinical relevance: HOARSI reliably identifies RAO‐affected horses in our population.  相似文献   

19.
Reasons for performing study: 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 pairs (one control, one treated horse) and exposed to the same environmental challenge (stabling, mouldy hay and dusty conditions). The treatment group received MRL‐EQ1 for 14 days while the control horses were untreated during the same period. In Phase 2, affected horses were ranked by severity of respiratory dysfunction and split randomly into either dexamethasone or MRL‐EQ1 treatment groups (n = 5/group). Bronchoalveolar lavage fluid, respiratory mechanic measurements, MRL‐EQ1 plasma concentration and tumour necrosis factor (TNF) whole blood activity were evaluated sequentially. Results: In Phase 1, MRL‐EQ1 did not prevent the occurrence of clinical signs and pulmonary inflammation. However, treatment was associated with a reduction in severity and a delay in the onset of signs and a reduction in pulmonary neutrophilia. In Phase 2, plasma concentrations achieved resulted in ex vivo suppression of lipopolysaccharide‐induced TNF production in equine blood. MRL‐EQ1 did not improve airway inflammation or lung function and was associated in a dose dependent manner with behavioural (depression, excitability) and blood changes (neutrophilia, increased serum muscle enzyme concentrations). Conclusions: Inhibition of p38 in the horse was partially effective in reducing clinical signs and airway inflammation when administered prior to, but not during clinical exacerbation in RAO. Potential relevance: Inhibitors of p38 MAPK with a better toxicity profile may be effective in the prevention or treatment of RAO.  相似文献   

20.
REASON FOR PERFORMING STUDY: The bronchodilator effects of trimetoquinol (TMQ) have been studied when administered i.v. or intratracheally, but not in an aerosolised form. OBJECTIVES: To define the relationship between the therapeutic and adverse responses (therapeutic index) of TMQ when administered as an aerosol or by the oral route. METHODS: Increasing doses of TMQ were administered to horses with heaves as an aerosol and by the oral route. Dose ranged 100-1000 microg/horse for aerosolised TMQ and from 6-60 microg/kg bwt for the oral route. Airway and cardiac effects were assessed by measurement of maximal change in pleural pressure (deltaPplmax) and heart rate (HR), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action of aerosolised (1000 pg/horse) and oral (6-60 microg/kg bwt) TMQ was evaluated over 6 h. RESULTS: Aerosol administration of TMQ caused dose-dependent bronchodilation but did not change HR or cause other observable side effects. When 1000 microg/horse was administered via aerosol, TMQ produced a 2-phase bronchodilation; an immediate effect lasting up to 30 min and a second phase between 2 and 4 h. Oral TMQ was therapeutically ineffective. CONCLUSION: Aerosol administration of TMQ is a safe and effective method of producing bronchodilation in horses.  相似文献   

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