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

BACKGROUND: Ciclesonide is a glucocorticoid prodrug, already registered for human use. Due to its mode of action and inhaled route of administration, it was considered an appropriate treatment option for horses with severe equine asthma. Although the efficacy of inhaled ciclesonide has been demonstrated in horses with asthma exacerbations under controlled mouldy hay challenge conditions, it has not yet been reported under field conditions. OBJECTIVES: To assess the effectiveness and safety of inhaled ciclesonide for the treatment of severe equine asthma. STUDY DESIGN: Prospective, multicentre, placebo-controlled, randomised, double-blinded study. METHODS: Two-hundred and twenty-four client-owned horses with severe equine asthma were randomised (1:1 ratio) to receive either ciclesonide inhalation (343 µg/actuation) solution or placebo (0 µg/actuation). Treatments (placebo or ciclesonide) were administered with a nonpressurised Soft Mist™ inhaler specifically developed for horses (Aservo® EquiHaler® ) at doses of 8 actuations twice daily for the first 5 days and 12 actuations once daily for the following 5 days. Primary outcome was a success/failure analysis with the a priori definition of treatment success as a 30% or greater reduction in weighted clinical score (WCS) between Day 0 and Day 10 (±1). RESULTS: The treatment success rate (as defined above) in ciclesonide-treated horses was 73.4% (80/109) after 10 (±1) days of treatment, being significantly higher than in the placebo group with 43.2% (48/111; P < 0.0001). Few systemic and local adverse events of ciclesonide were observed. MAIN LIMITATIONS: The severity of clinical signs of severe equine asthma varies over time; despite the prohibition of environmental management changes during the study, a placebo effect was also identified. This potentially contributed, in part, to the clinical improvement observed in the ciclesonide-treated group. CONCLUSIONS: Ciclesonide inhalation solution administered by the Aservo® EquiHaler® effectively reduced severity of clinical signs in a majority of horses with severe equine asthma and was well tolerated.

Comparative anatomy of the mammalian neuromuscular junction.

The neuromuscular junction (NMJ)-a synapse formed between lower motor neuron and skeletal muscle fibre-represents a major focus of both basic neuroscience research and clinical neuroscience research. Although the NMJ is known to play an important role in many neurodegenerative conditions affecting humans, the vast majority of anatomical and physiological data concerning the NMJ come from lower mammalian (e.g. rodent) animal models. However, recent findings have demonstrated major differences between the cellular anatomy and molecular anatomy of human and rodent NMJs. Therefore, we undertook a comparative morphometric analysis of the NMJ across several larger mammalian species in order to generate baseline inter-species anatomical reference data for the NMJ and to identify animal models that better represent the morphology of the human NMJ in vivo. Using a standardized morphometric platform ('NMJ-morph'), we analysed 5,385 individual NMJs from lower/pelvic limb muscles (EDL, soleus and peronei) of 6 mammalian species (mouse, cat, dog, sheep, pig and human). There was marked heterogeneity of NMJ morphology both within and between species, with no overall relationship found between NMJ morphology and muscle fibre diameter or body size. Mice had the largest NMJs on the smallest muscle fibres; cats had the smallest NMJs on the largest muscle fibres. Of all the species examined, the sheep NMJ had the most closely matched morphology to that found in humans. Taken together, we present a series of comprehensive baseline morphometric data for the mammalian NMJ and suggest that ovine models are likely to best represent the human NMJ in health and disease.