• Atul Gupta, Alies Sjoukes, David Richards, Winston Banya, Catherine Hawrylowicz, Andrew Bush, and Sejal Saglani.
• Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK. atulgupta@doctors.org.uk
• Am. J. Respir. Crit. Care Med. 2011 Dec 15; 184 (12): 134213491342-9.

RationaleLittle is known about vitamin D status and its effect on asthma pathophysiology in children with severe, therapy-resistant asthma (STRA).ObjectivesRelationships between serum vitamin D, lung function, and pathology were investigated in pediatric STRA.MethodsSerum 25-hydroxyvitamin D [25(OH)D(3)] was measured in 86 children (mean age, 11.7 yr): 36 with STRA, 26 with moderate asthma (MA), and 24 without asthma (control subjects). Relationships between 25(OH)D(3), the asthma control test (ACT), spirometry, corticosteroid use, and exacerbations were assessed. Twenty-two of 36 children with STRA underwent fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy with assessment of airway inflammation and remodeling.Measurements And Main Results25(OH)D(3) levels (median [IQR]) were significantly lower in STRA (28 [22-38] nmol/L) than in MA (42.5 [29-63] nmol/L) and control subjects (56.5 [45-67] nmol/L) (P < 0.001). There was a positive relationship between 25(OH)D(3) levels and percent predicted FEV(1) (r = 0.4, P < 0.001) and FVC (r = 0.3, P = 0.002) in all subjects. 25(OH)D(3) levels were positively associated with ACT (r = 0.6, P < 0.001), and inversely associated with exacerbations (r = -0.6, P < 0.001) and inhaled steroid dose (r = -0.39, P = 0.001) in MA and STRA. Airway smooth muscle (ASM) mass, but not epithelial shedding or reticular basement membrane thickness, was inversely related to 25(OH)D(3) levels (r = -0.6, P = 0.008). There was a positive correlation between ASM mass and bronchodilator reversibility (r = 0.6, P = 0.009) and an inverse correlation between ASM mass and ACT (r = -0.7, P < 0.001).ConclusionsLower vitamin D levels in children with STRA were associated with increased ASM mass and worse asthma control and lung function. The link between vitamin D, airway structure, and function suggests vitamin D supplementation may be useful in pediatric STRA.

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