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Indian Pediatr 2017;54: 29-32 |
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Association of Serum
Vitamin D Levels with Level of Control of Childhood Asthma
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TK Kavitha, *Nandita Gupta, Sushil K Kabra and Rakesh
Lodha
From the Departments of Pediatrics and
*Endocrinology, AIIMS, Ansari Nagar, New Delhi, India.
Correspondence to: Dr Rakesh Lodha, Professor,
Department of Pediatrics, All India Institute of Medical Sciences,
Ansari Nagar, New Delhi 110 029, India.
Email:
[email protected]
Received: January 25, 2016;
Initial review: March 26, 2016;
Accepted: November 24, 2016.
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Objective: To study the association between serum vitamin D
levels and levels of asthma control in children aged 5-15 years.
Methods: Children with physician-diagnosed asthma who were under
follow-up for at least 6 months were enrolled. Participants were
categorized into three asthma control groups as per standard guidelines,
and their serum 25-hydroxy vitamin D levels and pulmonary function tests
were compared. Results: Out of 105 children with asthma
enrolled in the study, 50 (47.6%) were controlled, 32 (30.5%) were
partly controlled and 23 (21.9%) were uncontrolled. Median (IQR) serum
vitamin D levels in these three groups were 9.0 (6.75, 15) ng/mL, 10
(6.25, 14.75) ng/mL and 8 (5, 10) ng/mL (P=0.24), respectively.
Conclusion: We did not observe any association of serum
25-hydroxy vitamin D levels with the level of control of childhood
asthma.
Key words: Diet, Management, Symptom control, Vitamin D
deficiency.
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V itamin D may have a role in asthma due to its
wide-ranging effects on airway epithelium, bronchial smooth muscle, and
immune cells central to the pathogenesis of asthma [1]. Information on
association between vitamin D and level of control of asthma in children
is scarce. We, therefore, studied the association between vitamin D
levels and level of control of asthma in children.
Methods
A cross-sectional study was performed from January
2013 to September 2014 in the Pediatric Chest Clinic of the Department
of Pediatrics at All India Institute of Medical Sciences (AIIMS), New
Delhi, India. Children with physician-diagnosed asthma, aged 5-15 years,
who had been in regular follow-up in the clinic for at least previous
six months were enrolled into the study after ruling out chronic
illness, clinical rickets or evidence of vitamin D supplementation in
last six months, and after getting informed written consent. We planned
to enroll a convenience sample of 100 children. The study protocol was
approved by the Ethics Committee of the institute.
Detailed clinical history was obtained; this included
dietary habits of the child and numbers of hours spent in outdoor during
daytime to evaluate the sunlight exposure to the child. Respiratory
system examination was performed.
Nutritional status of the child was assessed based on WHO
growth charts [2].
Spirometry was performed using Master Screen IOS (CareFusion,
San Diego, California, USA). We categorized participants into different
asthma control groups based on the Global (GINA) guidelines after
assessing the symptoms status in the previous four weeks. Blood samples
(2.5 mL) were collected in the study population in two plain vials.
Serum was separated by centrifuging the sample at -4 ºC
and was analyzed on the same day for levels of 25-hydroxy vitamin D
[25(OH)D] and parathyroid hormone (PTH). Serum calcium, inorganic
phosphate and alkaline phosphatase were analyzed on the same day using
spectrophotometric analysis. Serum level of 25(OH)D was measured using
chemiluminiscence by using LIAISON (DiaSorin, Italy). Serum 25(OH)D
level of more than 20 ng/mL was considered sufficient, level between 12
and 20 ng/mL as insufficient, and value less than 12 ng/mL was
considered as deficient [3,4].
Data were collected on structured performa and
managed using MS Excel software. Statistical analysis was performed
using Stata 11.0 (Stata Corp, College Station, TX). We used descriptive
statistics for the characteristics of the subjects. Fisher’s exact test/
chi-squared test were used for proportions. For continuous variables,
ANOVA or Kruskal-Wallis test were used to assess statistical
significance based on the distribution of variable (normal and
non-normal, respectively). Vitamin D levels in children with different
levels of control were compared by Kruskal-Wallis equality of population
rank test.
Results
A total of 108 children were enrolled into the study;
3 children were excluded from analysis because blood sample was not
collected. The characteristics of the 105 enrolled children are shown in
Table I.
TABLE I Comparison of Characteristics of Study Subjects Classified by the Asthma Control Status
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Asthma Control Status |
|
Whole Group |
Controlled |
Partly |
Uncontrolled |
P value |
|
(n=105) |
(n=50) |
controlled |
n=23 |
|
|
|
|
n=32 |
|
|
Age, in years; mean (SD) |
10.6 (2.4) |
10.8 (2.5) |
10.0 (2.5) |
11 (2.2) |
0.92 |
Onset of symptoms in years; mean (SD) |
3.2 (2.6) |
3.0 (2.7) |
3.1 (2.3) |
3.6 (2.7) |
0.59 |
Family History of asthma (%) |
57 (54.3%) |
29 (58%) |
16 (50%) |
12 (52.2%) |
0.76 |
Allergic Rhinitis; n (%) |
61 (58.1%) |
24 (48%) |
18 (56.3%) |
19 (82.6%) |
0.017 |
Cough; n (%) |
27 (25.7%) |
8 (16%) |
8 (25%) |
11 (47.8%) |
0.018 |
Wheeze; n (%) |
12 (11.4%) |
1 (2%) |
5 (15.6%) |
6 (26.1%) |
0.004 |
Breathlessness; n (%) |
12 (11.4%) |
1 (2%) |
5 (15.6%) |
6 (26.1%) |
0.004 |
Nasal Symptoms; n (%) |
9 (8.5%) |
2 (4%) |
3 (9.4%) |
4 (17.4%) |
0.14 |
Chest pain; n (%) |
8 (7.6%) |
0 (0%) |
5 (15.6%) |
3 (13.0%) |
0.006 |
BMI, kg/m2; mean (SD) |
16.6 (3.2) |
16.6 (3.1) |
16.5 (3.9) |
16.7 (2.6) |
0.95 |
Severity of Asthma |
|
|
|
|
|
Mild; n (%) |
26 (24.8%) |
11 (22%) |
8 (25%) |
7 (30.4%) |
0.76 |
Moderate; n (%) |
62 (59.0%) |
31 (62%) |
20 (62.5%) |
11 (47.8%) |
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Severe; n (%) |
17 (16.2%) |
8 (16%) |
4 (12.5%) |
5 (21.7%) |
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Number of Hospital Admissions in past 1 yr; n |
10 |
4 |
1 |
5 |
0.14 |
Number of emergency visits in past 1 yr; n |
19 |
8 |
2 |
9 |
0.52 |
Exacerbations in 1 yr; Median (IQR) |
1 (0, 2) |
1 (0, 2) |
1 (0, 2) |
2 (1, 4) |
0.03 |
Steroid bursts in 1 yr; Median (IQR) |
0 (0, 1) |
0 (0, 1) |
0 (0, 1) |
0 (0, 1) |
0.86 |
Steroid (Budesonide) Current Use (mcg/d); Median (IQR) |
400 (100, 800) |
400 (100, 800) |
400 (100, 700) |
400 (200, 800) |
0.30 |
Duration of use of Inhaled steroids in months; Median (IQR) |
28 (19, 36) |
26 (18, 36) |
26.5 (21, 36) |
33 (24, 45) |
0.127 |
Symptoms used to assess control |
|
|
|
|
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Day time Symptoms >2/wk; n (%) |
11 (10.4%) |
0 |
0 |
11 (47.8%) |
<0.0001 |
Nocturnal Symptoms (Any); n (%) |
36 (34.3%) |
0 |
14 (43.8%) |
22 (95.7%) |
<0.0001 |
Limitation of Activities (Any); n (%) |
29 (27.6%) |
0 |
11 (34.4%) |
18 (78.3%) |
<0.0001 |
Need for Rescue >2/wk; n (%) |
20 (19.1%) |
0 |
4 (12.5%) |
16 (69.6%) |
<0.0001 |
PFT Abnormality; n (%) |
27 (25.7%) |
0 |
12 (37.5%) |
15 (65.2%) |
<0.0001 |
Abbreviations: PFT: Pulmonary function test; SD: standard deviation; IQR: Interquartile range.
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Asthma status of 50 (47.6%) children were categorized
as controlled, 32 (30.5%) as partly controlled, and 23 (21.9%) as
uncontrolled. Table II compares the pulmonary function
tests (PFT) values between these groups.
TABLE II Pulmonary Function Tests in Children With Different Levels of Control of Asthma
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|
Asthma Control Status |
|
Whole group |
Controlled |
Partly controlled |
Uncontrolled |
P value |
|
(n=105) |
(n=50) |
(n=32) |
(n=23) |
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PFT Abnormality; n (%) |
27 (25.7%) |
0 (0%) |
12 (37.5%) |
15 (65.2%) |
<0.0001 |
Percentage Predicted FEV1; Mean (SD) |
87.7 (17.4) |
94.1 (15.7) |
83.3 (16.3) |
80.1 (17.9) |
0.0009 |
Percentage Predicted PEFR; Mean (SD) |
84.7 (26.8) |
93.8 (27.9) |
74.5 (16.7) |
78.9 (29.8) |
0.0025 |
Percentage Predicted FEV1/FVC; Mean (SD) |
95.9 (11.8) |
99.9 (8.3) |
94.4 (11.6) |
89.4 (15.2) |
0.001 |
Percentage Predicted FVC; Mean (SD) |
91.3 (16.4) |
94.1 (14.6) |
87.8 (20.1) |
89.8 (13.5) |
0.22 |
Percentage Predicted FEF 25; Mean (SD) |
57.9 (25.7) |
64.7 (21.6) |
52.0 (24.2) |
51.2 (32.7) |
0.033 |
Percentage Predicted FEF 75; Mean (SD) |
81.6 (25.5) |
91.2 (21.3) |
73.8 (22.0) |
71.4 (31.1) |
0.0007 |
FEV1: Forced Expiratory Volume-1 second; FVC:
Forced Vital Capacity; PEFR: Peak Expiratory Flow Rate; FEF75:
Forced Expiratory Flow 75; FEF25: Forced Expiratory
Flow 25.
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The median (IQR) serum 25(OH)D level in the study
participants was 9 (6,14) ng/mL. The median serum 25(OH)D levels were
comparable in the three groups based on control of asthma. The
prevalence of vitamin D deficiency in uncontrolled asthma group was
higher with 78.2% children being vitamin D deficient (P=0.52) (Table
III).
TABLE III Vitamin D in Different Asthma Control Groups
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Asthma Control Status |
Characteristic |
Controlled |
Partly Controlled |
Uncontrolled |
P value |
|
(n=50) |
(n=32) |
(n=23) |
|
Serum 25(OH)D (ng/mL); Median (IQR) |
9.0 (6.75, 15) |
10 (6.25, 14.75) |
8 (5, 10) |
0.24 |
Serum PTH (pg/mL); Median (IQR) |
46.3 (33.0, 64.4) |
39.7 (29.9, 55.2) |
40.9 (28.9, 62.1) |
0.65 |
Vitamin D status, n (%) |
Sufficient - (25(OH)D >20 ng/mL) |
5 (10%) |
1 (3.1%) |
1 (4.3%) |
|
Insufficient - (25(OH)D 12-19 ng/mL) |
13 (26%) |
11 (34.8%) |
4 (17.4%) |
|
Deficient - (25(OH)D <12 ng/mL) |
32 (64%) |
20 (62.5%) |
18 (78.26%) |
0.52 |
None of the major spirometric parameters showed
statistically significant correlation with serum vitamin D level except
FEF 25 (% predicted) (r=
0.22; P=0.02) and PEFR (r=0.19; P=0.049).
The asthma control subgroups did not show any
significant seasonal differences with the time of sampling. Median (IQR)
cumulative inhaled steroid use were 423 (214.5, 684) mg, 456 (241.5,
576) mg, and 363 (330, 600) mg in deficient, insufficient and sufficient
vitamin D status groups (P=0.98). Daily sunlight exposure was
comparable in vitamin D sufficient participants and others (P=0.97).
Discussion
We did not observe any significant association
between serum vitamin D levels and the level of asthma control in
children. We also did not observe any correlation between the 25(OH)D
levels and various spirometric parameters (percent predicted) except for
a statistically significant positive correlation of vitamin D levels
with FEF 25 and PEFR values
(% predicted).
Limitation of our study was a small sample size. We
did not collect detailed information about dietary intakes, particularly
vitamin D, and did not measure serum IgE levels. We did not have healthy
children as controls as we compared the levels of vitamin D in children
with various levels of control of asthma.
In a case-control study, Awasthi, et al. [5]
reported significant association between asthma control and vitamin D
deficiency. In another study, vitamin D levels were lower in children
with severe treatment resistant asthma as compared to moderate asthma
group and control subjects [6]. In a cross-sectional study among 100
children, Searing, et al. [7] reported positive correlation
between vitamin D levels and FEV 1
(percent predicted) and FEV1/FVC.
On the other hand, a study done in Thailand by Krobtrakulchai, et al.
[8] in 125 asthmatic children, vitamin D levels were similar between
three asthma control groups, and there was no association between
vitamin D levels and PFT values. Recent trials in children and adults
with asthma have also failed to demonstrate the effect of vitamin D
supplementation on symptom control [9,10].
We conclude that there is unlikely to be any
association between vitamin D levels and the control of asthma in
children.
Contributors: TKK: study design, data collection
and writing of manuscript; RL, SKK: designed the study, analyzed the
data and wrote the manuscript; NG: laboratory assays and writing of
manuscript.
Funding: None; Competing interest: None
stated.
What This Study Adds?
• Vitamin D deficiency was not found to have
any association with asthma control in Indian children.
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