SH Lock, AB Kay and NC Barnes
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, UK.

Patients with severe asthma who require long-term oral corticosteroid therapy are at risk of unwanted effects. Several immunosuppressive drugs have been assessed as corticosteroid-sparing agents in chronic asthma. We previously showed that cyclosporin A (CsA) administered for 12 wk improved lung function in corticosteroid-dependent patients. We have now investigated the corticosteroid-sparing properties of CsA over a 36-wk period. Following a 4-wk run-in period, 39 corticosteroid- dependent asthmatic patients were randomized to receive CsA (19 patients, initial doses 5 mg/kg/d) or matched placebo (20 patients) for 36 wk. Attempts were then made by a physician ignorant of the trial therapy to reduce their prednisolone dosages at 14-d intervals, provided that a patient's asthma remained stable or improved. Three patients receiving CsA had to be withdrawn from the study before they completed 12 wk of therapy. The remaining 16 patients achieved a statistically significant reduction in median daily prednisolone dosage of 62% (10 to 3.5 mg), compared with a decrease of 25% (10 to 7.5 mg) in the patients taking placebo (p = 0.043). This reduction was most pronounced during the last 12 wk of active therapy. In addition, morning peak expiratory flow rate (PEFR) improved significantly (mean 9.4%, SEM 3.0%) in the active-treatment group but not in the placebo group (p = 0.026 between groups). Predictable changes in renal function and blood pressure, and an increased incidence of hypertrichosis and paresthesia, were observed in the patients treated with CsA, but these did not necessitate withdrawal from the study, and were reversed during a 4-wk run-out period. Thus, low-dose CsA therapy, as compared with placebo, allowed a significant reduction in oral corticosteroid dosages in patients with severe asthma, and also improved lung function.

This article has been cited by other articles:

				E. D. Bateman, S. S. Hurd, P. J. Barnes, J. Bousquet, J. M. Drazen, M. FitzGerald, P. Gibson, K. Ohta, P. O'Byrne, S. E. Pedersen, et al. Global strategy for asthma management and prevention: GINA executive summary Eur. Respir. J., January 1, 2008; 31(1): 143 - 178. [Abstract] [Full Text] [PDF]

				E. M. Erin, B. R. Leaker, G. C. Nicholson, A. J. Tan, L. M. Green, H. Neighbour, A. S. Zacharasiewicz, J. Turner, E. S. Barnathan, O. M. Kon, et al. The Effects of a Monoclonal Antibody Directed against Tumor Necrosis Factor-{alpha} in Asthma Am. J. Respir. Crit. Care Med., October 1, 2006; 174(7): 753 - 762. [Abstract] [Full Text] [PDF]

				S. Wenzel Severe Asthma in Adults Am. J. Respir. Crit. Care Med., July 15, 2005; 172(2): 149 - 160. [Abstract] [Full Text] [PDF]

				S. Ying, L.N. Khan, Q. Meng, N.C. Barnes, and A.B. Kay Cyclosporin A, apoptosis of BAL T-cells and expression of Bcl-2 inasthmatics Eur. Respir. J., August 1, 2003; 22(2): 207 - 212. [Abstract] [Full Text] [PDF]

				R H Green, C E Brightling, I D Pavord, and A J Wardlaw Management of asthma in adults: current therapy and future directions Postgrad. Med. J., May 1, 2003; 79(931): 259 - 267. [Abstract] [Full Text] [PDF]

				A. S. Niven and G. Argyros Alternate Treatments in Asthma Chest, April 1, 2003; 123(4): 1254 - 1265. [Full Text] [PDF]

				Y. Fujitani and A. Trifilieff In Vivo and In Vitro Effects of SAR 943, a Rapamycin Analogue, on Airway Inflammation and Remodeling Am. J. Respir. Crit. Care Med., January 15, 2003; 167(2): 193 - 198. [Abstract] [Full Text] [PDF]

				A. Pahl, M. Zhang, K. Torok, H. Kuss, U. Friedrich, Z. Magyar, J. Szekely, K. Horvath, K. Brune, and I. Szelenyi Anti-Inflammatory Effects of a Cyclosporine Receptor-Binding Compound, D-43787 J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 738 - 746. [Abstract] [Full Text] [PDF]

				P.J. Barnes Cytokine modulators as novel therapies for airway disease Eur. Respir. J., July 2, 2001; 18(34_suppl): 67S - 77s. [Abstract] [Full Text] [PDF]

				L. N. KHAN, O. M. KON, A. J. MACFARLANE, Q. MENG, S. YING, N. C. BARNES, and A. BARRY KAY Attenuation of the Allergen-induced Late Asthmatic Reaction by Cyclosporin A Is Associated with Inhibition of Bronchial Eosinophils, Interleukin-5, Granulocyte Macrophage Colony-Stimulating Factor, and Eotaxin Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1377 - 1382. [Abstract] [Full Text] [PDF]

				Other drugs for severe asthma and unconventional therapies Can. Med. Assoc. J., November 1, 1999; 161(90111): s39 - 43. [Full Text]

				S. E. WENZEL, L. B. SCHWARTZ, E. L. LANGMACK, J. L. HALLIDAY, J. B. TRUDEAU, R. L. GIBBS, and H. W. CHU Evidence That Severe Asthma Can Be Divided Pathologically into Two Inflammatory Subtypes with Distinct Physiologic and Clinical Characteristics Am. J. Respir. Crit. Care Med., September 1, 1999; 160(3): 1001 - 1008. [Abstract] [Full Text]

				I. Balfour-Lynn Difficult asthma: beyond the guidelines Arch. Dis. Child., February 1, 1999; 80(2): 201 - 206. [Full Text]

				V. Patella, A. Giuliano, J.-P. Bouvet, and G. Marone Endogenous Superallergen Protein Fv Induces IL-4 Secretion from Human Fc{epsilon}RI+ Cells Through Interaction with the VH3 Region of IgE J. Immunol., November 15, 1998; 161(10): 5647 - 5655. [Abstract] [Full Text] [PDF]

				B. Gilbert, C Knight, F. Alvarez, C Waldrep, J. Rodarte, V Knight, and W. Eschenbacher Tolerance of volunteers to cyclosporine A-dilauroylphosphatidylcholine liposome aerosol Am. J. Respir. Crit. Care Med., December 1, 1997; 156(6): 1789 - 1793. [Abstract] [Full Text]

				M E Coren, M Rosenthal, and A Bush The use of cyclosporin in corticosteroid dependent asthma Arch. Dis. Child., December 1, 1997; 77(6): 522 - 523. [Abstract] [Full Text]

				F. G. Rolfe, J. E. Valentine, and W. A. Sewell Cyclosporin A and FK506 Reduce Interleukin-5 mRNA Abundance by Inhibiting Gene Transcription Am. J. Respir. Cell Mol. Biol., August 1, 1997; 17(2): 243 - 250. [Abstract] [Full Text]