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Editor,—In cystic fibrosis (CF) chronic respiratory infection is countered by an intense inflammatory reaction. Systemic steroids have been shown to improve lung function and reduce morbidity in patients with CF and reduce markers of chronic inflammation1 2; however, there are significant side effects associated with their long term use. Low dose cyclosporin A (CyA) has been shown to be effective in the treatment of inflammatory and autoimmune diseases, corticosteroid dependent chronic severe asthma in adults, and refractory childhood asthma.3
We report six paediatric CF patients where CyA had been used as a steroid sparing agent. These patients were on treatment with high dose inhaled or nebulised steroids prior to the commencement of oral steroids, and repeated attempts at reducing the steroid dose were unsuccessful. All patients exhibited steroid related complications including Cushingoid features, growth suppression, impaired glucose tolerance, hypertension, osteoporosis, and bone fractures. The dosage of CyA was adjusted to maintain whole blood trough levels between 100 and 150 ng/ml, using CyA doses ranging from 2 to 37 mg/kg/day.
In the four patients who benefited from CyA therapy the mean steroid dose decreased from 0.86 mg/kg/day in the one month prior to commencement of CyA to 0.30 mg/kg/day six months later and 0.25 mg/kg/day 12 months later. These patients were able to discontinue oral steroids within 18 months of commencement of CyA. Two patients did not show a reduction in mean steroid dosage, one of which underwent a successful heart–lung transplantation.
In the four patients who responded to CyA, lung function was maintained or improved, as were Chrispin–Norman chestx ray scores. Height velocity was also improved. Three patients did develop transient renal impairment, of whom only one required discontinuation of CyA. This was dose related and reversible but is infrequent with lower dose regimens used for anti-inflammatory therapy.4 Other side effects due to CyA were minimal, including mild hypertrichosis and gingival hyperplasia. There was no evidence of hypertension, hepatotoxicity, or neurotoxicity. The side effect profile of CyA is no more severe than for other immunosuppressive agents.
It is evident that CyA is a powerful but potentially toxic therapeutic agent and its use should be balanced against the risks of the disease and the long term use of steroids. These results suggest that CyA can be beneficial as a steroid sparing agent in CF patients; these data may be of help to the clinician in comparable clinical circumstances.
We are grateful to Dr CE Daman-Willems, Dr R Dinwiddie, Prof JF Price, Dr HA Wyatt, and Dr GJ Connett for allowing us to use their patients in this report.