PURPOSE OF THE STUDY.
To evaluate the relationship between serum vitamin D, lung function, and airway remodeling pathology in pediatric severe, therapy-resistant asthmatics (STRA).
Studied were 86 children, aged 6 to 16 years, 36 with STRA, 26 with moderate asthma (MA), and 24 without asthma (control). STRA was defined as those receiving at least 800 μg of inhaled steroids (beclomethasone equivalent) per day and additional controller medications. MA was defined as well-controlled asthma on <800 μg of beclomethasone equivalent per day.
Serum 25-hydroxyvitamin D [25(OH)D3] was measured. Symptom control was assessed by the childhood asthma control test (ACT). Acute asthma exacerbations were defined as requiring high-dose oral steroids for at least 3 days in the past 6 months. Spirometry was performed in accordance with ATS guidelines. Bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy was performed in 22 children with STRA, and nonasthmatic controls were included (bronchoscopy for other reasons). Differences between the 3 groups were assessed by using one-way analysis of variance or Kruskal-Wallis test.
Levels of 25(OH)D3 were significantly lower in STRA than in MA and control subjects (P < .001) and were positively associated with lung function, indicated by percent predicted forced expiratory volume in 1 second (P < .001) and forced vital capacity (P = .002), and with ACT scores (P < .001). An inverse relationship was noted between 25(OH)D3 levels and asthma-related exacerbation (P < .001), as well as inhaled steroid dose used (P = .001) in the MA and STRA groups. Finally, there was an inverse relationship between 25(OH)D3 and airway smooth muscle (ASM) mass (P = .008), although study did not indicate a relationship between 25(OH)D3 and tissue eosinophils, neutrophils, or mast cells. Additional assessment of ASM mass showed an inverse correlation with ACT score (P < .001) and a positive correlation with bronchodilator reversibility (P = .009).
This study demonstrates that lower serum 25(OH)D3 levels are associated with increased asthma severity, increased asthma-related exacerbations, and higher inhaled glucocorticoid requirements. Furthermore, decreased serum 25(OH)D3 levels resulted in worse lung function and poorer asthma control. Within the STRA group, low serum 25(OH)D3 levels were associated with increased ASM mass but not with other parameters of airway remodeling or airway inflammation.
This study provides additional data to support the association between vitamin D status and asthma severity and control. This study takes its results a step further from previous literature by evaluating aspects of airway pathology in children with STRA. Much of the existing literature in pediatric asthma and vitamin D has concentrated on vitamin D as a potential modulator of immune function or a modifier of sensitivity to glucocorticoids. However, some studies have reported that low vitamin D levels are negatively associated with airflow, bronchodilator responsiveness, and airway hyperresponsiveness. Overall, a number of proposed mechanisms could explain the link between vitamin D levels and ASM hypertrophy. Future research to refine and test the present hypotheses is needed. The reader should look in the same journal for the Pulmonary Perspective: “Vitamin D and Asthma” (Grace P, Brehm JM, Alcorn JF, Holguín F, Aujla SJ, and Celedón JC. Am J Respir Crit Care Med. 2011;185:124–132), an excellent review of current experimental and epidemiologic evidence of a causal association between vitamin D status and asthma, including potential protective mechanisms such as antiviral effects and enhanced steroid responsiveness.
- Copyright © 2012 by the American Academy of Pediatrics