Nebulisation of dexamethasone sodium phosphate for the treatment of severe asthmatic horses

Abstract

Summary Background Inhaled corticosteroids are effective in the treatment of equine asthma. A recent study reported that nebulisation of injectable dexamethasone had low systemic bioavailability in healthy horses and could represent a cost‐effective therapy for equine inflammatory lung diseases. Objectives To determine the effects of dexamethasone nebulisation on lung function in severe asthmatic horses. It was hypothesised that dexamethasone administered by nebulisation would be more effective than the same dose administered orally. Study design Randomised blinded experimental study in severe asthmatic horses. Methods Twelve severe asthmatic horses in clinical exacerbation were randomly assigned to treatment with 5 mg of dexamethasone sodium phosphate by nebulisation (n = 6) or by oral administration (n = 6), once daily for 7 days. Lung function was evaluated at baseline, after four treatment days (D4) and 24 h after the last dose (D8). The presence of residual bronchospasm was assessed on D8 with N‐butylscopolammonium bromide administration (0.3 mg/kg i.v.). A respiratory clinical score was performed daily. Serum cortisol concentration was measured at baseline, D4 and D8. Results The pulmonary elastance was unchanged in both groups while pulmonary resistance was significantly improved in the oral group on D8 (mean reduction in 1 cm H2O/L/s [CI: 0.34–1.65, P = 0.003]). All horses had residual bronchospasm at the end of the study. There was a group difference in the respiratory clinical score as it was significantly reduced in the oral group, from D5 to D8. Serum cortisol concentration decreased in all subjects. Main limitations Low number of horses and lack of placebo group. Conclusions Considering the lack of improvement of lung function and the hypothalamic‐pituitary‐adrenal axis suppression, the results of this study do not support aerosolisation of an injectable form of dexamethasone for the treatment of severe equine asthma at the dose and with the nebuliser evaluated.

Nebulized dexamethasone sodium phosphate in the treatment of horses with severe asthma

“…The dose of dexamethasone (5 mg) selected for our study was chosen for comparative purposes with previous published reports. 13,14 This dose may have been too low to be effective in horses with asthma but, although higher dosages may result in lung function improvement, suppression of the hypothalamo-pituitary-adrenal axis could negate the advantages of the inhaled route. Furthermore, with higher doses, because both the PO and nebulized routes would have resulted in improved lung function, 29 it would not have been possible to determine the contribution of lung deposition and absorption of the drug on the effects observed.…”

“…To conclude, the absence of improvement with nebulized dexamethasone in our study is in agreement with the previous report using a different nebulizer. 14 Both studies show that this treatment modality is not effective for horses with severe asthma and does not offer an advantage over systemically-administered dexamethasone. The characteristics of the injectable dexamethasone solution studied could…”

“…13 However, when evaluated for the treatment of horses with severe asthma, nebulized dexamethasone failed to improve lung function parameters after 7 days of treatment. 14 Furthermore, it was associated with a decrease in basal serum cortisol concentration, suggesting potentially adverse systemic effects. The main differences between these 2 studies were the horses' clinical status and the nebulizers used to deliver dexamethasone.…”

Glucocorticoid treatment in horses with asthma: A narrative review

“…42 The oral administration of a low dose (5 mg) of injectable dexamethasone for a week improves the lung function and the clinical score of horses with SEA, although to a magnitude insufficient for clinical use. 25 Given the poor improvement observed with the oral administration of the injectable dexamethasone, 25,35 it is advisable to administer products intended for oral use. Interestingly, the bioavailability of dexamethasone powder is better than that of the injectable forms in fasting horses, whereas it is similar when they are fed.…”

“…However, when inhaled GC are directly compared to appropriate systemic administration, the latter is never inferior, but often superior. 17 , 18 , 23 , 24 , 25 Instances where inhaled administration is more effective involve comparison with either prednisone, 26 which is not bioavailable in horses 27 or the long‐acting formulation of dexamethasone 21‐isonicotinate, which was possibly used at too low a dose according to the authors. 28 Furthermore, it is expected that systemic administration should result in a faster and greater improvement in horses suffering from severe airway obstruction in which mucus accumulation, bronchospasm, and cough might impair lower airways deposition of inhaled medication.…”