Relationship between Serum Vitamin D, Disease Severity, and Airway Remodeling in Children with Asthma

摘要

Rationale. Little is known about vitamin D status and its effect on asthma pathophysiology in children with severe, therapy-resistant asthma (STRA). Objectives: Relationships between serum vitamin D, lung function, and pathology were investigated in pediatric STRA. Methods: Serum 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 endo-bronchial biopsy with assessment of airway inflammation and remodeling. Measurements and Main Results: 25(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, (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 retic-ular 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). Conclusions: Lower 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.