Effect of different doses of inhaled ciclesonide on lung function, clinical signs related to airflow limitation and serum cortisol levels in horses with experimentally induced mild to severe airway obstruction

Abstract

Summary Background Inhaled corticosteroids are effective for the treatment of equine asthma but they induce cortisol suppression with potential side effects. Objectives To study the efficacy of ciclesonide, an inhaled corticosteroid with an improved safety profile, on lung function, clinical signs related to airway obstruction, and serum cortisol levels in asthmatic horses exposed to a mouldy hay challenge. Study design Cross‐over placebo controlled, blinded, randomised experiment. Methods Sixteen horses were enrolled in three subsequent dose‐titration studies (8 horses/study) to investigate the effects of inhaled ciclesonide administered for 2 weeks at doses ranging from 450 to 2700 μg twice daily or 3712.5 μg once daily. Systemic dexamethasone (0.066 mg/kg per os) was our positive control. A placebo group was also studied. Lung function and clinical scores were blindly performed before and after 7 and 14 days of treatment. Serum cortisol was measured before and after 3, 5, 7, 10, 14 days of treatment as well as 3 and 7 days post treatment. Results After 7 days, dexamethasone induced a significant reduction in pulmonary resistance (from 2.5 ± 0.6 at day 0 to 1.1 ± 0.7 cm H2O/L/s), pulmonary elastance (5.0 ± 2.6 to 1.2 ± 1.0 cm H2O/L), and of the weighted clinical score (14.8 ± 4.7 to 8.0 ± 4.4). Similarly, ciclesonide 1687.5 μg twice daily significantly improved pulmonary resistance (2.7 ± 1.1 to 1.6 ± 0.8 cm H2O/L/s), pulmonary elastance (5.2 ± 3.1 to 2.2 ± 1.3 cm H2O/L), and weighted clinical score (13 ± 2.9 to 10.8 ± 4.2). Serum cortisol suppression (<50 nmol/L) systematically occurred with dexamethasone from day 3 of treatment up to day 3 post treatment, but not with ciclesonide at any tested doses. Placebo did not exert any significant beneficial effect. Main limitations Experimentally induced asthma exacerbations in horses might respond differently to treatment than naturally occurring exacerbations. Conclusions Inhaled ciclesonide is an effective treatment for horses with equine asthma. Serum cortisol was unaffected by treatment.

Equine Asthma: Current Understanding and Future Directions

“…Indeed, 19 years ago, Robinson et al found that even in horses with historical severe EA, clinical score failed to reflect low-grade airway obstruction, and suggested that without easily used, field-accessible testing equipment, lower airway disease would go underdiagnosed ( 53 ). Recently, the adapted 23-point scoring system has been shown to be the most useful in discriminating mild from severe cases, but it is unlikely to distinguish normal from subclinical disease ( 54 ), and the IDEASS scoring system has recently been described as a useful scoring system for moderate-to-severe equine asthma ( 55 ). Thus, while clinical scoring is essential to a good examination and careful research, and can potentially be useful in measuring response to treatment in the individual, it is insufficient in making the phenotypic distinction between mildly affected horses and healthy horses.…”

Inhaled ciclesonide is efficacious and well tolerated in the treatment of severe equine asthma in a large prospective European clinical trial

“…The adopted "responder criterion" was based on data derived from the previously published dose finding studies, 27 in which oral dexamethasone, regarded as "gold standard", as well as ciclesonide, but not placebo administration, resulted in a greater than 30% improvement in both lung resistance (RL) and mean WCS, in the face of continued induced environmental challenge. This threshold was also confirmed in a pilot study, in which responder rate was 70.8%…”

Pulmonary response of severely asthmatic horses after intra‐articular administration of methylprednisolone

“…[12][13][14][15][16] Corticosteroids have been the subject of numerous studies related to joint disease treatment and respiratory problems. [17][18][19][20][21][22] Triamcinolone acetonide (TA), methylprednisolone acetate (MPA) and betamethasone acetate are primarily used for intra-articular injection. 23 A 2009 survey regarding joint therapy in equine practice reported that 73% of equine practitioners use TA in higher motion joints and 73% MPA in lower motion joints.…”

“…Corticosteroids have been the subject of numerous studies related to joint disease treatment and respiratory problems 17‐22 . Triamcinolone acetonide (TA), methylprednisolone acetate (MPA) and betamethasone acetate are primarily used for intra‐articular injection 23 .…”