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Cyclosporin A (Sandimmun®) in chronic severe steroid-dependent asthma
Abstracts Asthma
284
CYCLOSPORIN A (SANDIMMUN ~') IN CHRONIC SEVERE STEROID-DEPENDENT ASTHMA. A Alexander, NC BARNES, AB Kay, Dept. of Allergy and Clinical Immunology, National Heart and Lung Institute and London Chest Hospital, London, UK. There is increasing evidence for a role for activated CD4 +ve Tlymphocytes and their products in asthma. We have therefore undertaken a double blind, placebo-controlled trial of CyA (initial dose 5mg/kg/day) in severe corticosteroid dependent asthma. All patients had documented asthma, required long-term maintenance oral prednisolone and had impaired lung function. Following a 4-week runin period subjects received CyA (n=17) or placebo (n=16) for 12 weeks. In the CyA group morning peak expiratory flow rate (PEFR) rose steadily from week 2 onwards with an increase of 27.2% at week 12 (probability = 0.0027). In the placebo group there was a nonsignificant 9% increase in PEFR at week 12. Similar results were seen with evening PEFR, PEFR after bronchodilator and forced expiratory volume in one second. There was a trend toward less rescue courses of oral prednisolone in the CyA group (CyA 5/17, placebo 10/16). There was a mean 10% fall in glomerular filtration rate (GFR) in the CyA group. We conclude that CyA is an effective treatment in severe steroid-dependent asthma causing a clinically significant improvement in lung function. This result lends support to a role for T-lymphocytes in asthma.
285
CYCLOSPORIN A {CyA} INHIBITS AIRWAY EOSINOPHILIA ALLERGIC GUINEA-PIGS. R. B o u h e l a l , K. H o s h i k o , J . M o r l e y , K. B o u b e k e u r ~ [Basel a n d Geneva}
IN
It is now reeognised that even mild asthmatics have extensive inflammation
of the airways in which eosinophfls are prominent. Eosinophilie inflammation eharacterlses the response of sensifised guinea-pigs to inhaled allergen. In s u e h animals, pre-treatment with CyA by oral (10 m g / k g / d a y for 6 days], or inhaled [4 mg/kg] routes diminished airway eosinophilia. Following inhalation of allergen, s u c h animals show heightened reactivity to airway spasmogens. This phenomenon w a s not influenced by administration of CyA [10 m g / k g / d a y for 6 days], even though eosinophilia was suppressed. The pharmaeological profile of CyA in allergic inflammation resembles that of a prophylaetie a n t i - a s t h m a drug. xxxvii
284
CYCLOSPORIN A (SANDIMMUN ~') IN CHRONIC SEVERE STEROID-DEPENDENT ASTHMA. A Alexander, NC BARNES, AB Kay, Dept. of Allergy and Clinical Immunology, National Heart and Lung Institute and London Chest Hospital, London, UK. There is increasing evidence for a role for activated CD4 +ve Tlymphocytes and their products in asthma. We have therefore undertaken a double blind, placebo-controlled trial of CyA (initial dose 5mg/kg/day) in severe corticosteroid dependent asthma. All patients had documented asthma, required long-term maintenance oral prednisolone and had impaired lung function. Following a 4-week runin period subjects received CyA (n=17) or placebo (n=16) for 12 weeks. In the CyA group morning peak expiratory flow rate (PEFR) rose steadily from week 2 onwards with an increase of 27.2% at week 12 (probability = 0.0027). In the placebo group there was a nonsignificant 9% increase in PEFR at week 12. Similar results were seen with evening PEFR, PEFR after bronchodilator and forced expiratory volume in one second. There was a trend toward less rescue courses of oral prednisolone in the CyA group (CyA 5/17, placebo 10/16). There was a mean 10% fall in glomerular filtration rate (GFR) in the CyA group. We conclude that CyA is an effective treatment in severe steroid-dependent asthma causing a clinically significant improvement in lung function. This result lends support to a role for T-lymphocytes in asthma.
285
CYCLOSPORIN A {CyA} INHIBITS AIRWAY EOSINOPHILIA ALLERGIC GUINEA-PIGS. R. B o u h e l a l , K. H o s h i k o , J . M o r l e y , K. B o u b e k e u r ~ [Basel a n d Geneva}
IN
It is now reeognised that even mild asthmatics have extensive inflammation
of the airways in which eosinophfls are prominent. Eosinophilie inflammation eharacterlses the response of sensifised guinea-pigs to inhaled allergen. In s u e h animals, pre-treatment with CyA by oral (10 m g / k g / d a y for 6 days], or inhaled [4 mg/kg] routes diminished airway eosinophilia. Following inhalation of allergen, s u c h animals show heightened reactivity to airway spasmogens. This phenomenon w a s not influenced by administration of CyA [10 m g / k g / d a y for 6 days], even though eosinophilia was suppressed. The pharmaeological profile of CyA in allergic inflammation resembles that of a prophylaetie a n t i - a s t h m a drug. xxxvii