Ontogenesis of evolved changes in respiratory physiology in deer mice native to high altitude.

High-altitude environments are cold and hypoxic, and many high-altitude natives have evolved changes in respiratory physiology that improve O2 uptake in hypoxia as adults. Altricial mammals undergo a dramatic metabolic transition from ectothermy to endothermy in early post-natal life, which may influence the ontogenetic development of respiratory traits at high altitude. We examined the developmental changes in respiratory and haematological traits in deer mice (Peromyscus maniculatus) native to high altitude, comparing the respiratory responses to progressive hypoxia between highland and lowland deer mice. Among adults, highlanders exhibited higher total ventilation and a more effective breathing pattern (relatively deeper tidal volumes), for mice that were caught and tested at their native altitudes and those lab-raised in normoxia. Lab-raised progeny of each population were also tested at post-natal day (P)7, 14, 21 and 30. Highlanders developed an enhanced hypoxic ventilatory response by P21, concurrent with the full maturation of the carotid bodies, and their more effective breathing pattern arose by P14; these ages correspond to critical benchmarks in the full development of homeothermy in highlanders. However, highlanders exhibited developmental delays in ventilatory sensitivity to hypoxia, hyperplasia of type I cells in the carotid body and increases in blood haemoglobin content compared with lowland mice. Nevertheless, highlanders maintained consistently higher arterial O2 saturation in hypoxia across development, in association with increases in blood-O2 affinity that were apparent from birth. We conclude that evolved changes in respiratory physiology in high-altitude deer mice become expressed in association with the post-natal development of endothermy.

Ventilation and gas exchange before and after voluntary static surface breath-holds in clinically healthy bottlenose dolphins, Tursiops truncatus.

We measured respiratory flow (V̇), breathing frequency (fR), tidal volume (VT), breath duration and end-expired O2 content in bottlenose dolphins (Tursiops truncatus) before and after static surface breath-holds ranging from 34 to 292 s. There was considerable variation in the end-expired O2, VT and fR following a breath-hold. The analysis suggests that the dolphins attempt to minimize recovery following a dive by altering VT and fR to rapidly replenish the O2 stores. For the first breath following a surface breath-hold, the end-expired O2 decreased with dive duration, while VT and fR increased. Throughout the recovery period, end-expired O2 increased while the respiratory effort (VT, fR) decreased. We propose that the dolphins alter respiratory effort following a breath-hold according to the reduction in end-expired O2 levels, allowing almost complete recovery after 1.2 min.

Growth of preweaned, group-housed dairy calves diagnosed with respiratory disease using clinical respiratory scoring and thoracic ultrasound-A cohort study.

The objectives of this cohort study were to identify a cut point on a previously described 6-level ultrasound score (USS6) at which average daily gain (ADG) is affected and to determine whether there is any additional benefit of using a clinical respiratory score. Calves from a commercial herd in Ohio were enrolled at entry to an automated calf feeder barn at (mean ± standard deviation) 21 ± 6 d of age (n = 308). Calves that survived until 50 d (n = 233) were included in the analyses. Twice-weekly health exams included a clinical respiratory score (CRS), USS6 (0-5, based on lung mass involved), and body weight. For the CRS, the nose, eyes, ears, cough, and rectal temperature were assigned a score (0-3), and calves were considered positive (CRS+) when at least 2 areas scored ≥2. For analysis, USS6 and CRS status were based on a calf's first bovine respiratory disease event identified during the study period. The first multivariable linear model was fit to determine whether USS6 was associated with ADG and controlled for CRS. We detected no difference in ADG among calves with USS6 scores of 2, 3, 4, and 5. Based on this finding, we proposed a simplified 2-level ultrasound score (USS2; without lung consolidation or with lung consolidation ≥1 cm2). A second multivariable model was fit to assess the association between USS2 and ADG; this model controlled for CRS, birth weight category, breed, and cohort. Calves with lung consolidation (n = 169) had lower ADG than calves without lung consolidation (n = 64; 0.73 vs. 0.85 kg/d, respectively). Calves that were CRS+ (n = 61) had lower ADG than calves that were CRS- (n = 172; 0.74 vs. 0.84 kg/d, respectively). Although CRS did not affect the relationship between USS2 and ADG, both CRS and USS2 are necessary to explain variation in ADG. We simplified USS6 and proposed USS2 based on how lung consolidation affected ADG. A simplified 2-level ultrasound score may be more practical for veterinarians to identify calves that may be at risk for poor growth. The effect on ADG was similar between calves with lung consolidation and calves identified as CRS+. Therefore, both thoracic ultrasonography and CRS should be used to identify calves with all types of respiratory disease that affect growth. However, this study represents calves in group housing from 21 to 50 d of age on 1 farm with high disease incidence. We encourage studies that investigate the effects of lung consolidation and CRS on ADG in different management systems.

Outcomes and prognostic factors of surgical treatments for brachycephalic obstructive airway syndrome in 3 breeds.

OBJECTIVE: To determine prognostic indicators for the surgical treatment of brachycephalic obstructive airway syndrome (BOAS) and to compare the prognosis of 2 multilevel surgical procedures. STUDY DESIGN: Prospective clinical study. SAMPLE POPULATION: Client-owned pugs, French bulldogs, and bulldogs (n = 50). METHODS: Noninvasive whole-body barometric plethysmography (WBBP) was used to assess respiratory function before, 1 month and 6 months after upper airway corrective surgery. Postoperatively, BOAS indices (ie, ascending severity score generated from WBBP data, 0%-100%) that equaled to or exceeded the cut-off values of BOAS in the diagnostic models were considered to have a "poor prognosis." A multivariate logistic regression was used to assess predictors for prognosis. RESULTS: The median BOAS indices decreased after surgery (from 76% to 63%, P < .0001), although dogs with indices in this range would still be considered clinically affected. Age (odds ratios [OR] = 0.96, 95% confidence interval [CI]: 0.93-0.99, P < .05), body condition (OR = 0.06, 95% CI: 0.01-0.39, P < .01), laryngeal collapse (OR = 6.1, 95% CI: 1-37.22, P < .05), and surgical techniques (OR = 7.94, 95% CI: 1.17-54.01, P < .05) were associated with postoperative prognosis. The multivariate model suggests modified multilevel surgery (MMS) may have a better outcome than traditional multilevel surgery (TMS) (P = .034). The positive predictive value of the logistic model was 84% (95% CI: 68-94%) and the area under the receiver operating characteristic (ROC) curve was 89% (95% CI: 78-99%, P <.0001). CONCLUSIONS: Younger age, normal body condition, presence of laryngeal collapse, and treatment with TMS were negative prognostic factors after surgical treatment of BOAS. MMS is recommended, particularly in dogs with a higher probability of poor prognosis.

Reliability of breath by breath spirometry and relative flow-time indices for pulmonary function testing in horses.

BACKGROUND: Respiratory problems are common in horses, and are often diagnosed as a cause of poor athletic performance. Reliable, accurate and sensitive spirometric tests of airway function in resting horses would assist with the diagnosis of limitations to breathing and facilitate investigations of the effects of various treatments on breathing capacity. The evaluation of respiratory function in horses is challenging and suitable procedures are not widely available to equine practitioners. The determination of relative flow or flow-time measures is used in paediatric patients where compliance may limit conventional pulmonary function techniques. The aim of the current study was to characterise absolute and relative indices of respiratory function in healthy horses during eupnoea (tidal breathing) and carbon dioxide (CO2)-induced hyperpnoea (rebreathing) using a modified mask pneumotrachographic technique well suited to equine practice, and to evaluate the reliability of this technique over three consecutive days. Coefficients of variation, intra-class correlations, mean differences and 95% confidence intervals across all days of testing were established for each parameter. RESULTS: The technique provided absolute measures of respiratory function (respiratory rate, tidal volume, peak inspiratory and expiratory flows, time to peak flow) consistent with previous studies and there was no significant effect of day on any measure of respiratory function. Variability of measurements was decreased during hyperpnea caused by rebreathing CO2, but a number of relative flow-time variables demonstrated good agreement during eupnoeic respiration. CONCLUSIONS: The technique was well tolerated by horses and study findings suggest the technique is suitable for evaluation of respiratory function in horses. The use of relative flow-time variables provided reproducible (consistent) results, suggesting the technique may be of use for repeated measures studies in horses during tidal breathing or rebreathing.

Technical note: A facility for respiration measurements in cattle.

A respiration system consisting of 4 climate-controlled chambers and 1 set of flowmeters and analyzers was constructed and validated. Each chamber had volume of 21.10m(3) (3.68×2.56×2.24m) and was made from steel with double-glazed windows on either side enabling visual contact between animals. The chambers are independently climate-controlled and can maintain temperature and relative humidity in a range from 5 to 45°C and 30 to 80%, respectively. A flow generator and mass flowmeter continuously pull air from each chamber and a slight negative pressure inside the chamber is ensured. Air from all chambers and ambient air share a common gas analysis and data acquisition system for monitoring O2, CO2, and CH4 concentrations over the measurement period, with the cycle time set to 20min. Analyzers are regularly calibrated and the chambers have mean recoveries of 99.0 and 98.0% for CO2 and CH4, respectively. The chambers are equipped with infrared cameras and electronic feed and water bins for intake measurements, as well as sensors for monitoring animal position and heart rate. Data acquisition and analysis software is used to calculate the rate of consumption of O2 and production of CO2 and CH4. The dynamic respiration measurements are integrated with feed intake data and other sensors. The daily gas exchanges are estimated by integration to determine methane emission and heat production. We conducted a trial with 12 lactating 3/4 Holstein × 1/4 Gyr crossbred dairy cows (6 multiparous and 6 primiparous) under 2 feeding regimens (ad libitum or restricted) to validate the system. Two 22-h respiration measurements were obtained from each cow. Restricted-fed cows showed lower values for milk yield, methane emission, and heat production compared with ad libitum-fed animals. We found no difference between groups for CH4 produced per kilogram of dry matter intake. Repeatability for CH4 emission and heat production was high (0.97 and 0.92, respectively). The respiration system described herein is a useful tool for measuring the dynamic and accumulated data of heat production, methane emission, and feed intake.

Cardiopulmonary Effects of Laparoscopic Ovariectomy of Variable Duration in Cats.

OBJECTIVE: To evaluate the cardiopulmonary effects of low-pressure (6 mmHg) peritoneal insufflation of varying duration in healthy cats during ovariectomy (OVE). STUDY DESIGN: Prospective, randomized study. ANIMALS: Female cats (n = 24). METHODS: After anesthesia induction, cats had short (Short LAP; n = 8) or long duration (Long LAP; n = 8) laparoscopic ovariectomy, or Open OVE (Open; n = 8) for comparison. Hemodynamic and pulmonary measurements were recorded after induction of anesthesia (T0), 5 minutes after abdominal insufflation had reached 6 mmHg of pressure (T1), after the 2nd ovary had been resected (T2), after abdominal decompression (T3), and at the end of anesthesia, after abdominal closure (T4). Hemodynamic and pulmonary variables were compared between groups. RESULTS: Low-pressure abdominal insufflation caused cardiopulmonary changes in cats. At T1 and T2, Long LAP and Short LAP caused a significant change in PvCO2 and RC when compared with Open. During T3, RC was lower only in Long LAP. At T2, there was decrease in SV, but not CO for Long LAP when compared with Open. CONCLUSIONS: Duration of insufflation was associated with worsening of negative cardiopulmonary effects; however, these effects were reversible and resolved by the end of the procedure.

Early experience with continuous positive airway pressure (CPAP) in 5 horses -- a case series.

This case series is the first report of the use of CPAP (continuous positive airway pressure) ventilation in adult horses. Two horses and 3 ponies anesthetized for orthopedic procedures in lateral recumbency received 10 cm H(2)O CPAP. During anesthesia, arterial oxygen partial pressure tended to increase and arterial carbon dioxide pressure tended to increase despite increased minute ventilation index. The measured cardiovascular parameters were within physiologic limits.

Accelerometry estimates field metabolic rate in giant Australian cuttlefish Sepia apama during breeding.

1. Estimating the metabolic rate of animals in nature is central to understanding the physiological, behavioural and evolutionary ecology of animals. Doubly labelled water and heart-rate methods are the most commonly used approaches, but both have limitations that preclude their application to some systems. 2. Accelerometry has emerged as a powerful tool for estimating energy expenditure in a range of animals, but is yet to be used to estimate field metabolic rate in aquatic taxa. We combined two-dimensional accelerometry and swim-tunnel respirometry to estimate patterns of energy expenditure in giant Australian cuttlefish Sepia apama during breeding. 3. Both oxygen consumption rate (Vo2) and swimming speed showed strong positive associations with body acceleration, with coefficients of determination comparable to those using similar accelerometers on terrestrial vertebrates. Despite increased activity during the day, field metabolic rate rarely approached Vo2, and night-time Vo2 was similar to that at rest. 4. These results are consistent with the life-history strategy of this species, which has a poor capacity to exercise anaerobically, and a mating strategy that is visually based. With the logistical difficulties associated with observation in aquatic environments, accelerometry is likely to prove a valuable tool for estimating energy expenditure in aquatic animals.

[Pulmonary function testing in the cat - an overview]. / Lungenfunktionsmessung bei der Katze ­ eine Übersicht.

This article provides an overview of currently available pulmonary function tests in cats, divided into invasive and non-invasive methods. Invasive techniques comprise arterial blood gas analysis and measurement of pulmonary mechanics. Non-invasive techniques include pulse oximetry and capnography, as well as methods not yet integrated into everyday practice such as tidal breathing airflow-volume loops, whole-body barometric plethysmography and thorax compression. In this article, the background, execution, interpretation, and limitations of each test are discussed. Proper performance and assessment of pulmonary function measurements may aid in understanding the pathophysiology of feline respiratory disease and in increasing objectivity when assessing the existing disease and treatment efficacy.

Particle deposition in the lung of the Göttingen minipig.

We report on particle deposition in the tracheobronchial and pulmonary regions of the respiratory tract of the minipig and its dependence on particle size. Four animals breathing spontaneously via the nose were exposed for 1 h to known concentrations of three different polydisperse dry aerosols composed of bovine serum albumin (BSA) and an oxide of a rare earth element: Y2O3, Sm2O3, and Er2O3. The mass size distributions of the rare earth elements of the three test aerosols have mass median aerodynamic diameters of 0.9, 2.5, and, 4.3 microm, and geometric standard deviations of sigma(g) = 2.0, 1.8, and, 1.7. The extrathoracic, tracheobronchial, and pulmonary regions of the respiratory tract were dissected, separately lyophilized, and chemically digested by microwave-assisted high pressure digestion. The tracer element in each compartment was determined by inductively coupled plasma mass spectrometry. A mass balance equation relating the tracer mass found in the lung compartments to the tracer mass inhaled was solved by linear regression to obtain the deposition fraction as function of particle sizes for the tracheobronchial and the pulmonary lung region. Estimated values for the respiratory minute volume were used in this context. For coarse particles > 6 microm, the deposition fraction is < 5% for both compartments. The deposition fraction for particles with aerodynamic diameter of approximately 3 microm is 21% in the tracheobronchial airways and 40% in the pulmonary airways.

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 collagen fiber type and distribution within the walls of the noncartilagenous bronchioles. The health status of 14 horses was characterized by clinical respiratory exam, bronchoalveolar lavage cytology, and pulmonary function tests. Following postmortem examination and histological assessment, horses were divided into RAO-affected (n = 4) and nonaffected (n = 10) groups. Eight sections per horse from all lung regions were evaluated histologically. Results of the study showed that collagens I and III were present in the lamina propria and adventitial area of the noncartilaginous bronchioles. There was clear staining differentiation between collagen I or III, airway smooth muscle, and the airway epithelium. Collagen I and III were present in the lamina propria and adventitial areas of the noncartilaginous bronchioles of horses, and there was no significant difference in the relative amount of collagen I and III between this group of RAO-affected and nonaffected horses.

Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses.

OBJECTIVE: To evaluate experimental induction of recurrent airway obstruction (RAO) with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses. ANIMALS: 7 horses with and 3 horses without a history of RAO. PROCEDURES: 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 spores derived from 3 fungi, lipopolysaccharide, and 1-microm silica microspheres in all horses. This was followed by a 4-month washout period and a further pulmonary function test followed by saline (0.9% NaCl) solution challenge and bronchoalveolar lavage. RESULTS: Lichtheimia corymbifera, Aspergillus fumigatus, and Eurotium amstelodami were consistently identified in cultures of moldy hay. Nebulization with fungal spores, lipopolysaccharide, and microspheres induced significant increases in pleural pressure in RAO-susceptible but not control horses. Airway neutrophilia developed in both groups of horses with exposure to challenge material but more severely in RAO-susceptible horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that inhalation of fungal spores in combination with lipopolysaccharide and silica microspheres can induce disease exacerbation in susceptible horses and may thus be a useful model for future standardized studies of RAO in horses.

Clinical Application of Pulmonary Function Testing in Small Animals.

Pulmonary function tests (PFTs) are important diagnostic tools that have wide clinical applications in human and veterinary medicine. Widespread use of PFTs in measuring lung volumes in veterinary medicine was historically limited by the need for specialized equipment to accurately perform and interpret these tests, and by lack of patient cooperation. However, recent advances and modifications have allowed PFTs to be safely performed in conscious veterinary patients with minimal stress. This article focuses on the most commonly used tests of pulmonary function including tests of pulmonary mechanics and of gas exchange in the lungs.

Comparison of analyses of respiratory gases made with the K4b2 portable and Quark laboratory analysers in horses.

Measurements of minute ventilation (VE) and expired oxygen and carbon dioxide fractions (FeO2 and FeCO2) were measured at rest and during exercise in seven warmblood horses performing two consecutive standardised incremental treadmill exercise tests at submaximal speed, using the portable K4b2 telemetric unit and the laboratory Quark metabolic cart in random order. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were estimated using the Haldane equation. There were no significant differences between the measurements made with the two devices. However, VE was overestimated when the horses were cantering at 10 m/s in comparison with values available in the literature.

Contribution of lung function tests to the staging of severe equine asthma syndrome in the field.

Staging methods are useful tools for monitoring disease and response to treatment, and because Severe Equine Asthma Syndrome (SEAS) has a high prevalence in the equine population, a clinical staging method can provide important information to optimize equine care. Our team has previously developed and published a clinical staging method for SEAS and in the present study we further evaluated information provided by lung function tests, in order to determine their contribution to disease staging. Using discriminant analysis we set out to produce a new staging method with applicability in the field. Differences between group means (P < .05) were observed for clinical score, bronchoalveolar lavage fluid neutrophil percentage, pleural pressure (ΔPpl), PaO2 and histamine concentration and the linear functions obtained explained 99.3% of the data variability, with 94.7% of cases grouped correctly and a cross-validation of 86.8%. Thus this staging model showed very good results and the discriminant linear functions may be used to identify and stage SEAS. This method can be used in the field and also in diagnostic and research centres.

The relationship between bronchoalveolar lavage fluid cytology and airway hyper-reactivity in a population of Australian horses presented for poor performance.

OBJECTIVE: To investigate the relationship between bronchoalveolar lavage fluid cytology, particularly mast cells, and airway hyper-reactivity in athletic horses presented for poor performance that included a respiratory tract evaluation in two disparate locations in Australia. DESIGN: Multi-centre, retrospective and prospective cross-sectional study METHODS: Eighty four adult horses underwent both pulmonary function testing and histamine bronchoprovocation with a commercial flowmetric plethysmography system. A bronchoalveolar lavage was performed four to twelve hours later. Bronchoalveolar lavage fluid cytology was categorised using two differing classification systems to define mild equine asthma. Statistical analysis was used to assess associations between bronchoalveolar lavage fluid relative inflammatory cell percentages, and airway hyper-reactivity and their associated categorisations. RESULTS: Sixty four percent (54/84) of horses displayed airway hyper-reactivity, as defined by PC35 < 6 mg/ml of histamine. A relative mastocytosis was the most common bronchoalveolar lavage fluid cytological abnormality. Horses with a sole mast cell response of ≥ 5% within their bronchoalveolar lavage fluid displayed airway hyper-reactivity at a lower dose of nebulized histamine than horses with normal bronchoalveolar lavage fluid cytology. Horses with mixed cell responses (relative mast cell percentage > 2% and/or relative neutrophil percentage > 5% and/or eosinophil relative cell percentage ≥ 1%) displayed airway hyper-reactivity at a lower dose of nebulized histamine than horses with normal bronchoalveolar lavage fluid cytology. CONCLUSION: In the Australian context, recently revised increased bronchoalveolar lavage fluid cytology relative cell percentage cut offs appear appropriate for sole mast cell responses. The historical lower cut offs appear to be appropriate for mixed inflammatory cell responses.

Randomised study of the immunomodulatory effects of azithromycin in severely asthmatic horses.

Neutrophilic inflammation is believed to contribute to the airway obstruction and remodelling in equine asthma. Azithromycin, an antibiotic with immunomodulatory properties, reduces pulmonary neutrophilia and hyper-responsiveness in human asthmatics and decreases airway remodelling in rodent models of asthma. It was therefore hypothesised that azithromycin would improve lung function, mucus accumulation and central airway remodelling by decreasing luminal neutrophilia in severe equine asthma. The effects of a 10-day treatment with either azithromycin or ceftiofur, an antimicrobial without immune-modulating activity, were assessed using a blind, randomised, crossover design with six severe asthmatic horses in clinical exacerbation. Lung function, tracheal mucus accumulation, tracheal wash bacteriology, bronchial remodelling, airway neutrophilia and mRNA expression of proinflammatory cytokines (interleukin (IL)-8, IL-17A, IL-1ß, tumour necrosis factor-α) in bronchoalveolar lavage fluid were evaluated. Azithromycin decreased the expression of IL-8 (P=0.03, one-tailed) and IL-1ß (P=0.047, one-tailed) but failed to improve the other variables evaluated. Ceftiofur had no effect on any parameter. The reduction of neutrophilic chemoattractants (IL-8, IL-1ß) justifies further efforts to investigate the effects of a prolonged treatment with macrolides on airway neutrophilia and remodelling. The lack of efficacy of ceftiofur suggests that severe equine asthma should not be treated with antibiotics at first-line therapy.

Effects of a MAPK p38 inhibitor on lung function and airway inflammation in equine recurrent airway obstruction.

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.

Pulmonary dysfunction and skeletal muscle changes in horses with RAO.

BACKGROUND: Chronic pulmonary diseases (recurrent airway obstruction [RAO]) have been reported to alter skeletal muscle cells in humans. The purpose of this study was to evaluate a potential relationship between pulmonary and muscle variables in horses with a clinical diagnosis of RAO. Muscle biopsies from healthy horses and from horses with RAO were investigated and the relationship between the severity of lung disease and the degree of muscular changes was determined. HYPOTHESIS: We hypothesized that chronic pulmonary disease can lead to changes of the skeletal muscle in horses. ANIMALS: Fifteen healthy horses (control) and 50 horses with RAO were examined. METHODS: In a prospective clinical trial, a complete lung examination was performed in all horses. In all horses, muscle enzyme activity at rest and after exercise and muscle biopsies from the M. gluteus medius were examined. RESULTS: None of the horses had clinical or histologic signs of primary or neurogenic myopathies. According to the clinical, endoscopic, and radiographic findings and with a scoring system, the horses with RAO were grouped according to the severity of pulmonary findings (15 horses mild, 24 horses moderate, 11 horses severe RAO). Pathologic changes of the skeletal muscle (fiber atrophy or fiber hypertrophy, myofibrillar degeneration, hyperplasia of mitochondria, and ragged-red-like fibers) were identified in most horses with RAO but in only a few individual control horses. In addition, a marked depletion of muscle glycogen storage was evident in the RAO horses but not in the control group. Other pathologic changes of skeletal muscle such as centralized nuclei and regenerating fibers were rare, but were more frequent in horses with lung diseases than in the control group. The degree of muscle cell changes was also graded with a scoring system and correlated with the severity of pulmonary disease (r= 0.55). CONCLUSION: Chronic pulmonary disease in horses is associated with structural changes in skeletal muscle. CLINICAL IMPORTANCE: Because chronic pulmonary disease may affect muscles, early and effective therapy may prevent these changes. This finding could be of clinical importance but requires further studies.