The effects of calcitriol treatment in glucocorticoid-resistant asthma

• Published in: Journal of allergy and clinical immunology 2014-06, Vol.133 (6), p.1755-1757.e4
• Main Authors: Nanzer, Alexandra M., MRCP, Chambers, Emma S., PhD, Ryanna, Kimuli, MRCP, Freeman, Anna T., MRCP, Colligan, Grainne, BSc, Richards, David F., MSc, Timms, Peter M., FRCPath, Martineau, Adrian R., PhD, Griffiths, Christopher J., FRCGP, Corrigan, Christopher J., PhD, Hawrylowicz, Catherine M., PhD
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Asthma; Asthma - drug therapy; Body mass index; Calcitriol - therapeutic use; Drug dosages; Drug Resistance; Glucocorticoids - therapeutic use; Humans; Mortality; Patients; Statistical methods; Vitamin D
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2014.03.015

A number of mechanisms have been proposed to contribute to glucocorticoid-resistant asthma, including increased expression of nuclear factor kappa B and activating protein 1 (AP-1), increased expression of histone deacetylase, polymorphisms in IL-10, increased expression of the dominant negative isoform of the glucocorticoid receptor beta (GRβ), and vitamin D insufficiency.2-4 Our earlier data showed that peripheral blood CD4+ T cells from glucocorticoid-resistant as compared with glucocorticoid-sensitive asthmatic patients failed to synthesize the anti-inflammatory cytokine IL-10 in response to glucocorticoid in vitro.5 The active form of vitamin D (calcitriol; 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]) when used in combination with glucocorticoid restored this IL-10 response both in vitro and ex vivo following patient ingestion of calcitriol.6 These data, together with epidemiologic evidence linking vitamin D insufficiency/deficiency with a poor clinical response to treatment in asthma,3,4 provided the rationale for this proof-of-concept clinical trial. On the one hand, the decision to study a well-characterized cohort of glucocorticoid-resistant asthmatic patients produced significant challenges with recruitment and retention, but on the other hand may have facilitated our ability to observe a clinical effect that may be manifest most clearly in this small but important subset of patients.\n Study subjects were asked to report any adverse events from the day of commencement of the first course of oral prednisolone until 4 weeks after the second course by telephone or e-mail or at study visits.