Pulmonary function,airway cytology and bronchoalveolar lavage fluid drug concentration after aerosol administration of cefquinome to horses

The administration of antibiotics by aerosol to horses suffering from respiratory infections may partially circumvent the limitations of antimicrobial therapy, e.g. large injection volumes, low bioavailability and risk of diarrhoea. Only injectable formulations are available currently and usually contain other substances that could irritate the mucosa and induce coughing and bronchospasm. In addition, the quality of the aerosol, particularly in terms of the delivery of antibiotics to the deep parts of the lung, is unknown. Although used under field conditions, cefquinome delivered by aerosol has never been studied in horses. This study examined the safety of cefquinome injectable solution, administered by aerosol at a dose of 225 mg/inhalation to 7 healthy horses, by assessing (1) pulmonary function before and 15 min after a single inhalation, at the first day (Day 1) and the fifth day (Day 5) of a 5 day period treatment; and (2) the inflammatory status of the lung, i.e. percentage neutrophils and myeloperoxidase concentration, based on bronchoalveolar lavage (BAL) at D1 and D5. In addition, cefquinome concentrations were measured in bronchoalveolar lavage fluid after aerosol, intravenous (i.v.) and intramuscular (i.m.) administrations. A single aerosol of cefquinome injectable solution did not induce any immediate nor delayed pulmonary side effects in healthy horses and produced cefquinome concentrations in bronchoalveolar lavage (BAL) within 30 min that were higher than the minimal inhibitory concentration of the main equine respiratory pathogens. These results should stimulate further studies, especially in horses suffering from bronchial hyper‐reactivity. Aerosol delivery of antibiotics may well have a role in equine therapeutics.     

The effects of three models of airway disease on tidal breathing flow-volume loops of thoroughbred horses

The effects of histamine and methacholine aerosols and of a fixed inspiratory resistance on tidal breathing flow-volume loops (TBFVL) were investigated using 18 unsedated, standing, healthy thoroughbred horses. The data were first analysed using traditional flow-volume loop indices and then reduced using standardized factor scoring coefficients obtained in a previous study in this laboratory using similar experimental techniques. On the basis of resting TBFVL analysis, the degree of pulmonary dysfunction caused by inhalation of histamine and methacholine aerosols with concentrations of 10 and 2 mg/ml, respectively, was similar. The fixed resistance also caused significant changes in the resting spirogram and TBFVL indices, suggesting that this model may prove valuable for further studies involving upper respiratory tract (URT) conditions.Administration of histamine and methacholine aerosols resulted in significant changes in all factor scores, although most of the observed changes were due to the effects of these aerosols on the respiratory rate. These findings re-emphasize the importance of the effects of respiratory rate on pulmonary mechanics. Application of the resistance resulted in significant changes in factor score 3, the inspiratory factor, which lends support to the validity of this model for URT conditions. The close agreement between the factor scores obtained under controlled conditions in this study and in a previous study in this laboratory confirms that the factor analysis used for both of these studies provides an adequate means of reducing TBFVL data obtained from thoroughbred horses.The large intra- and inter-individual variation observed both with the indices of TBFVL and with the factor scores limits the potential of these variables for detecting individual animals with obstructive airway disease. Re-evaluation of these indices under the stress of exercise may reduce the variability observed in these data and may increase the magnitude of differences between different animals, providing a means of detecting individual animals with subclinical obstructive airway conditions.Abbreviations CV coefficient of variation - P _pl,max maximal intrapleural pressure difference - FVL flow-volume loop - LRT lower respiratory tract - P _ao airway opening pressure - P _tp transpulmonary pressure - TBVFL tidal breathing flow-volume loop - URT upper respiratory tract - USPTM ultrasonic pneumotachometer     

The relationship between range of motion of lumbosacral flexion‐extension and canter velocity of horses on a treadmill

Reasons for performing study: Research into kinematics of the healthy equine back, has been performed in the walk and trot. This study focuses on back kinematics during canter, over a range of velocities. Flexion extension (FE) movements in canter are greatest in the lumbosacral (LS) region. Previous research has focused on canter velocity of 7 m/s; therefore quantification of LS kinematics at varying velocities is required to understand LS functions in equine locomotion. Hypothesis: Range of flexion‐extension movement through the lumbosacral joint increases with increasing velocity. Methods: Six Thoroughbred horses (mean age 9.6 years) cantered on treadmill at 4 velocities (6.0, 6.5, 7.0 and 8.0 m/s, respectively). Reflective markers were placed over the 5th lumbar vertebra (L5), the lumbosacral junction (LS) and the 3rd sacral vertebra (S3). Lumbosacral angle (LS) was defined as the angle formed between L5, LS and S3. Flexion‐extension (FE) range of motion (ROM) was analysed using a 2 camera, 3D motion capture system ProReflex¹. Linear regression was used to determine strengths of relationships between speed of canter and lumbosacral FE movements. Results: Range of FE ROM seen at the lumbosacral joint increased linearly with speed. FE ROM ranged 6.1°± 1.9 at 6 m/s, 6.3°± 1.9 at 6.5 m/s, 6.6°± 1.9 at 7 m/s and 7.2°± 1.9 at 8 m/s. Linear regression showed positive associations between speed and LS FE range of motion (r²= 0.993; P = 0.003). Conclusions and potential relevance: Results show linear relationships between LS FE movements and submaximal canter velocities. These results provide information on the LS joint at canter. Understanding the effects of velocity on the back of healthy horses may aid our understanding of the demands placed on this joint in sport horses at this gait.     

Correlation and discriminant analysis between clinical, endoscopic, thoracic X-ray and bronchoalveolar lavage fluid cytology scores, for staging horses with recurrent airway obstruction (RAO)

As recurrent airway obstruction (RAO) is progressive and as medical history is frequently unknown by owners, it's important to suggest a score model to characterize RAO stages for a more accurate diagnosis and treatment. The authors correlated clinical (CS), endoscopic (ES), thoracic X-ray (XRS) and bronchoalveolar lavage fluid (BALFS) scores in horses with RAO, in an attempt to establish relevance of each factor's contribution for the characterization of RAO stages and to suggest a staging method. Thirty horses with RAO and ten healthy controls were studied. Pearson correlation coefficients were determined between CS, ES, XRS and BALFS. Only significant correlation coefficients (>0.60) were considered. One way variance analyses were used to compare the two groups. A discriminant analysis model was adjusted on the RAO staging method suggested. There was a significant correlation coefficient between the CS cough, nostril flare and abdominal lift, all the mucus ES (0.61-0.84), the XRS interstitial pattern, bronchial radiopacity and thickening and tracheal thickening (0.67-0.78) and the BALFS neutrophil percentages (0.63-0.84). These variables (e.g., cough) which presented a significant correlation coefficient were considered relevant and chosen for a score model to characterize RAO stages. The ten healthy controls were attributed stage 0 and the 30 RAO horses were attributed stages 1 (4 horses), 2 (7 horses), 3 (10 horses) and 4 (9 horses). There was also a significant correlation coefficient between all the relevant variables and the RAO stage (0.61-0.89). Furthermore, discriminant analysis of the RAO staging method showed 92.5% of original grouped cases and 85.0% of cross-validated grouped cases correctly classified, having confirmed major contribution of the same variables that had significant correlation coefficients. Even though further confirmation by lung functional testing is desirable, the significant correlation between relevant variables and RAO stage and the results of RAO staging discriminant analysis support the suggestion of our score model for the characterization of RAO stages.     

Evaluation of basal plasma α‐melanocyte‐stimulating hormone and adrenocorticotrophic hormone concentrations for the diagnosis of pituitary pars intermedia dysfunction from a population of aged horses

Reasons for performing study: The sensitivity and specificity of basal plasma α‐melanocyte‐stimulating hormone (α‐MSH) and adrenocorticotrophic hormone (ACTH) for the diagnosis of pituitary pars intermedia dysfunction (PPID) has not been evaluated in a population‐based study. Objectives: To evaluate basal plasma α‐MSH and ACTH concentrations for the diagnosis of PPID in a population of horses aged ≥15 years. Methods: Owner‐reported data were obtained using a postal questionnaire distributed to an equestrian group. A subgroup of surveyed owners was visited and veterinary examination performed on horses aged ≥15 years. Blood samples were analysed for plasma α‐MSH and ACTH concentrations. Seasonally adjusted cut‐off values for α‐MSH and ACTH concentrations for the diagnosis of PPID were obtained using Youden index values against a clinical gold standard diagnosis (hirsutism plus 3 or more clinical signs of PPID). Results: α‐melanocyte‐stimulating hormone and ACTH were highly correlated with each other and with clinical and historical indicators of PPID. The increase in both α‐MSH and ACTH with increasing numbers of clinical signs in affected horses supports a spectrum of disease. Both variables were affected by season, with derived cut‐off values being higher in autumn compared with other seasons. Sensitivity and specificity were moderate and good in nonautumn seasons (59 and 93%, respectively) for α‐MSH using a cut‐off of 52.0 pmol/l. Sensitivity and specificity were good in nonautumn seasons (80 and 83%, respectively) for ACTH using a cut‐off of 29.7 pg/ml. For both α‐MSH and ACTH, sensitivity and specificity were close to 100% for samples obtained during the autumn period. Conclusions and potential relevance: Basal plasma α‐MSH and ACTH had moderate‐to‐good sensitivity and specificity for the diagnosis of PPID, which improved substantially during the autumn period, suggesting this may be the ideal time to test. Further studies to develop seasonally adjusted reference intervals for different geographical locations are warranted.