Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 29  |  Issue : 4  |  Page : 887-894

Effect of vitamin D supplementation on respiratory functions and laboratory parameters in asthmatic patients


1 Department of Physiology, Faculty of Medicine, Alazhar University, Cairo, Egypt
2 Department of Biochemistry, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt
3 Department of Physiology, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt

Date of Submission16-Mar-2015
Date of Acceptance04-Jul-2015
Date of Web Publication21-Mar-2017

Correspondence Address:
Eman I Elgizawy
Gamal Abd El Naser Street, Shebin El Kom, Menoufia, 32511
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.202487

Rights and Permissions
  Abstract 

Objectives
The present work was designed to investigate whether vitamin D status has a relationship with the pulmonary function test results of asthmatics and assess the impact of vitamin D on interleukin-10 (IL-10).
Background
The incidence of bronchial asthma and other allergic disorders has increased over the past decades in nearly all nations. Many studies have suggested the role of vitamin D deficiency in both T-helper-1 and T-helper-2 diseases. Asthma is characterized by a shift toward a Th2 cytokine-like disease, either as overexpression of Th2 or as underexpression of Th1; however, the association between vitamin D, IL-10, and asthma remains uncertain. In this study, the associations of vitamin D level and IL-10 with asthma were evaluated.
Patients and methods
This study was conducted on 75 adult participants, aged 18 years or above, who were divided into three groups. Group I consisted of 25 adults with bronchial asthma who were treated with a classic regimen; group II consisted of another 25 adults with bronchial asthma who were treated with a combination of classic regimen and vitamin D supplementation at a dose of 2000 IU (50 mg) for 3 months; and group III consisted of 25 adults who served as controls. All patients were assessed at the beginning of the study (groups Ia, IIa, and IIIa) and at the end of 3 months (groups Ib, IIb, and IIIb).
Results
There was an inverse relationship between BMI in asthmatic patients and vitamin D level. Vitamin D level had direct and significant correlations with both IL-10 (r1 = 0.206,P≤ 0.001) and predicted forced expiratory volume in 1 s (FEV1) (r2 = 0.083,P≤ 0.001). There were significant associations between vitamin D level and the number of hospitalizations or unscheduled visits (P < 0.05).
Conclusion
These results showed that serum 25-hydroxy vitamin D levels were deficient in asthmatics, and there was a direct and significant relationship between vitamin D levels, IL-10, and pulmonary function test outcomes in asthmatic patients.

Keywords: asthma, interleukin-10, vitamin D


How to cite this article:
Ashour FA, Badr EA, Donia SS, El-Hefnawy MY, Elgizawy EI. Effect of vitamin D supplementation on respiratory functions and laboratory parameters in asthmatic patients. Menoufia Med J 2016;29:887-94

How to cite this URL:
Ashour FA, Badr EA, Donia SS, El-Hefnawy MY, Elgizawy EI. Effect of vitamin D supplementation on respiratory functions and laboratory parameters in asthmatic patients. Menoufia Med J [serial online] 2016 [cited 2020 Feb 27];29:887-94. Available from: http://www.mmj.eg.net/text.asp?2016/29/4/887/202487


  Introduction Top


Bronchial asthma represents one of the most common chronic diseases and one of the major public health problems worldwide [1]. Approximately 250 000–345 000 people die every year from the disease [2]. It can place considerable restrictions on the physical, emotional, and social aspects of a patient's life [3]. It is a chronic inflammation associated with airway hyper-responsiveness and airway obstruction and remodeling. Persistent reductions in baseline airway function and increased airway responsiveness during childhood are associated with the development of asthma in adult life [4].

In the majority of patients control of asthma can be achieved with long-term maintenance medications [5].

However, a substantial proportion of patients do not achieve optimal asthma control despite high-dose treatment. In particular, inadequately controlled patients with severe persistent asthma are at high risk for severe exacerbations and asthma-related mortality. These patients represent the greatest unmet medical need in the asthmatic population [1].

New hypothesis links asthma to subnormal vitamin D level. Vitamin D has several effects on the innate and adaptive immune systems, which might be relevant in the primary prevention of asthma, in the protection against or reduction of asthma morbidity, and in the modulation of the severity of asthma exacerbations [6],[7]. Vitamin D also modulates regulatory T-cell (Treg cells) function and interleukin-10 (IL-10) production, which may increase the therapeutic response to glucocorticoids (GCs) in steroid-resistant asthma. IL-10 also regulates effector responses associated with established allergic and asthmatic disease, including inhibition of cytokine production by T-helper-2 cells (Th2) as well as mast cell and eosinophil function [8],[9].

Cross-sectional data have shown that low vitamin D levels in patients with mild to moderate asthma are correlated with poor asthma control, reduced respiratory function, reduced GC response, more frequent exacerbations, and consequently increased steroid use [10]. However, there is insufficient evidence to support a causal association between vitamin D status and asthma per se. More so, there are limited data on the impact of vitamin D status on the control and severity of asthma in adult patients [1]. The aims of this study were to prospectively investigate whether vitamin D status has a potential relationship with pulmonary function test (PFT) results of asthmatic patients and correlate the impact of vitamin D supplementation on immunity by evaluating human serum IL-10 levels.


  Patients and Methods Top


The work represented a cross-sectional study that was carried out on 75 adults aged 18 years or older, including 50 asthmatic patients recruited from the outpatient chest clinic and the inpatient department of Menoufia University Hospitals and 25 apparently matched healthy volunteers, all of whom were selected between April 2013 and May 2014. The study comprised 35 male (46.7%) and 40 female (53.3%) participants, with a mean age of 39.7 ± 2.4 years.

Bronchial asthma was diagnosed according to the criteria of the American Thoracic Society [11]. Written consent was obtained from all participants and controls after a full explanation of the study. Ethical approval was obtained from the local research ethics committee of the Faculty of Medicine, Menoufia University.

Selection of asthmatic patients in this study was based on the following

Inclusion criteria

To be eligible for inclusion in the study the participants had to be nonsmokers, had to have a clinical history of asthma confirmed by spirometry, and serum vitamin D level below normal (≤29 ng/ml).

Exclusion criteria

Patient refusal, having any major renal or hepatic or cardiac problem, intolerance of thorax or abdomen large pressure swing caused by PFT maneuvers, history of consumption of vitamin D supplements or drugs that modulate serum vitamin D levels, and having a disease affecting calcium and vitamin D levels were the exclusion criteria.

Participants were divided into three main groups:

Group I: Bronchial asthma–classic regimen-treated group

This group included 25 asthmatic patients (10 men and 15 women) who were maintained on their classic treatment regimen without any vitamin D supplementation. Their ages ranged from 22 to 62 years.

Group II: Bronchial asthma–classic regimen and vitamin D supplementation-treated group

This group included 25 asthmatic patients (12 men and 13 women) who were maintained on their classic regimen and concomitantly given a 2000 IU (50 mg) daily vitamin D supplement for 3 months [12]. Their ages ranged from 24 to 55 years.

All patients had to be on regular bronchial asthma classic treatment regimens (GCs, long-acting β2 agonists, and antileukotriene), with adjustment of dose according to severity.

Group III: the control group

This group included 25 apparently matched healthy volunteers (13 men and 12 women) without a history of any allergic disorders. Their ages ranged from 18 to 65 years.

All participants were assessed at the beginning of the study (groups Ia, IIa, and IIIa) and at the end of 3 months (groups Ib, IIb, and IIIb) for selected parameters in this study.

Methods

After obtaining the patient's consent, each participant was subjected to the following:

  • Full medical history, including demographic data such as name, age, sex, and BMI. BMI was calculated as weight in kilograms divided by the square of height in meters
  • Full clinical examination (general and chest examination)
  • Chest radiograph
  • Laboratory investigation
  • PFTs.


Biochemical analysis

Assay

  • Complete blood count was measured with a Pentra –80 automated blood counter (ABX, Paris, France). A peripheral smear was taken, stained, and eosinophils were counted
  • Erythrocyte sedimentation rate was determined by the classical Westergren method [13]
  • Random blood glucose, liver function tests, and renal function tests (serum creatinine and blood urea) were analyzed on an autoanalyzer (Synchron CX5) from Beckman (Beckman Instrument Inc., Scientific Instrument Division, Fullerton, California, USA) [4]
  • Serum vitamin D level was assessed by a radioimmunoassay (Cobra Quantum, Packard, Minnesota, Minnesota, USA)
  • Serum IL-10 level was assessed using an IL-10 enzyme-linked immunosorbent assay kit (ImmunoTools GmbH, Friesoythe, Germany).


Pulmonary function tests

All participants underwent PFTs in the pulmonary function test unit in Menoufia University Hospital using Quark PFT3 (Cosmed, Italy).

Spirometry interpretation

Spirometry tests were interpreted by examining the absolute values of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC, comparing them with predicted values, and examining the shape of the curves. Spirometry parameters were considered normal if they fulfilled the following criteria:

  • FEV1, FVC, and VC = 80% were 120% of the reference value (normal value for someone of that age, sex, height and ethnic group)
  • FEV1/FVC was 70 or higher.


Obstructive abnormality

Spirometric parameters compatible with airflow obstruction are:

  • FEV1/FVC less than 70
  • FEV1 less than 80% of the reference value.


Once the diagnosis of obstructive abnormality was made, the severity of obstruction and reversibility of obstruction were noted.

Obstruction was considered reversible when the FEV1 on the final test was higher than the FEV1 on the initial test by more than 12%, or is 200 ml [14].

Statistical methodology

The data collected were tabulated and analyzed by SPSS (Statistical Package for the Social Sciences), version 16 (SPSS Inc, Chicago, Illinois, USA). Descriptive statistics were expressed as mean and SEM and range. Analysis of variance was applied to compare data between two groups. Qualitative variables were expressed as number and percentage and analyzed with the c 2-test and correlation between parameter before and after test by paired t-test and correlation test (r). P values of 0.05 or less were considered significant.


  Results Top


The results of this study revealed that:

The mean age of group I was 41.7 ± 2.7 years, which was statistically nonsignificant (P > 0.05) when compared with the corresponding mean age of group III (39.48 ± 2.9 years). Notably, in group II, the mean age was 38.1 ± 2.3 years, which was statistically nonsignificant (P > 0.05) when compared with the corresponding mean ages of groups I and III ([Table 1]).
Table 1 Comparison of geometric data among the three studied groups

Click here to view


The proportion of male and female participants in group I was 40 and 60%, which was statistically nonsignificant (P > 0.05) when compared with the corresponding proportion in the control group (52 and 48%). Furthermore, in group II, the male and female proportions were 48 and 52%, respectively ([Table 1]).

The mean BMI in group I was 26.3 ± 0.8, which was statistically significantly higher (P < 0.01) when compared with the corresponding mean BMI in group III (21.2 ± 0.6). Furthermore, in group II, the mean BMI was 24.4 ± 1, which was statistically nonsignificant (P > 0.05) when compared with the corresponding mean BMI in group I ([Table 1] and [Figure 1].
Figure 1: Linear relationship between serum vitamin D and interleukin-10 (IL-10) level after fi nal assessment.

Click here to view


The mean serum vitamin D level in the initial assessment profile in group I was 24.1 ± 3.8 ng/ml, which was statistically significantly lower (P < 0.01) when compared with the corresponding mean value in group III (58.8 ± 4). Moreover, in group II, the mean value of vitamin D was 19.2 ± 1.2 ng/ml, which was statistically nonsignificant (P > 0.05) when compared with the corresponding mean value in group I ([Table 2]).
Table 2 Comparison of vitamin D level in initial and final assessment investigation among the three studied groups

Click here to view


The mean serum vitamin D level in the final assessment profile in group I was 25.3 ± 3.6 ng/ml, which was statistically significantly lower (P < 0.01) when compared with the corresponding mean value in group III (58.8 ± 4). Interestingly, in group II, the mean vitamin D level was 50.6 ± 2.06 ng/ml, which was statistically significantly higher (P < 0.001) when compared with the corresponding mean value in group I ([Table 2]).

The serum vitamin D level in group I in the final assessment stage was 25.3 ± 3.6 ng/ml, which was statistically nonsignificantly changed (P > 0.05) when compared with that in the initial assessment stage (24.1 ± 3.8 ng/ml). The serum vitamin D level in group II in the final assessment stage was 50.6 ± 2.06 ng/ml, which was statistically significantly higher when compared with the corresponding mean value of vitamin D in the initial assessment stage, which was 19.2 ± 1.2 ng/ml ([Table 2]).

The mean serum IL-10 level in the initial assessment profile in group I was 3.7 ± 0.7 pg/ml, which was statistically significantly lower (P < 0.01) when compared with the corresponding mean value in group III (12 ± 0.2 pg/ml). Furthermore, in group II, the mean serum IL-10 level was 3 ± 0.4 pg/ml, which was statistically nonsignificant (P > 0.05) when compared with the corresponding mean value in group I ([Table 3]).
Table 3 Comparison of serum interleukin-10 level in initial and final assessment among the three studied groups

Click here to view


The mean serum IL-10 level in the final assessment profile in group I was 3.8 ± 0.6 pg/ml, which was statistically significantly lower (P < 0.01) when compared with the corresponding mean value in group III (12 ± 0.2 pg/ml). Fortunately, in group II, the mean serum IL-10 level was 10.7 ± 0.6 pg/ml, which was statistically significantly higher (P < 0.001) when compared with the corresponding mean value in group I ([Table 3]).

Serum IL-10 level in group I in the final assessment stage was 3.8 ± 0.6 pg/ml. This was statistically nonsignificantly different (P > 0.05) when compared with that in the initial assessment stage (3.7 ± 0.6 pg/ml). IL-10 serum levels in subgroup IIb was 10.7 ± 0.3 pg/ml, which was statistically significantly higher when compared with the corresponding mean value of serum IL-10 in subgroup IIb, which was 3 ± 0.4 pg/ml ([Table 3]).

Furthermore, in the present study there was a positive correlation between serum vitamin D and IL-10 in group II [Figure 2].
Figure 2: Histograms showing comparison of FEV1 in initial and final assessment among the three studied groups.

Click here to view


FEV1 in group I in the initial assessment was 73.3 ± 8.72%, which was statistically nonsignificant (P > 0.05) when compared with that in the final assessment stage, which was 71.26 ± 8.72. FEV1 level in group II in the final assessment stage was 79.1 ± 0.55%, which was statistically significantly higher when compared with that in the initial assessment stage (71.26 ± 8.72) [Figure 3].
Figure 3: Histogram showing BMI in the three studied groups.

Click here to view



  Discussion Top


Asthma is a chronic disease with 300 million diagnoses around the world. It continues to be the foremost cause of morbidity, and the incidence appears to be growing despite treatment regimens in use [15].

Vitamin D has been thought to mediate the observed association between sun exposure and asthma. Vitamin D deficiency has been reported in many populations, even in those living in areas with abundant sun exposure [16].

In this study, the mean age of the studied patients suffering from asthma was 39.7 ± 2.4 years. The choice of age of the participations in this study was intended to be nonsignificant in relation to each other to exclude the age factor affecting other parameters that are to be investigated. Amelink et al. [17] found that asthma develops during childhood. However, its symptoms can appear at any time in one's life. Adults become sensitized to everyday substances found in their homes or food and suddenly begin to experience asthma symptoms. Adults tend to have lower lung capacity (the volume of air you are able to take in and forcibly exhale in 1 s) after middle age because of changes in muscles and stiffening of chest walls.

In this work the asthmatics comprised 35 male (46.7%) and 40 female (53.3%) patients. The choice of sex of the participations was intended to be nonsignificant in relation to each other to exclude the age factor affecting other parameters. Kynyk et al. [18] concluded that epidemiologic studies of asthma show a striking difference in asthma prevalence and severity closely related to sex, which interestingly seem to follow key transition points in the reproductive cycle of women. In general, the lifetime likelihood of developing asthma is about 10.5% greater in women than in men.

In this investigation, the mean BMI of the studied patients suffering from asthma was 25.35 ± 0.9, which was significantly higher when compared with that of the control group (21.2 ± 0.6), concluding an inverse relationship between BMI and asthmatic patients. These results were in agreement with those of Ciprandi et al. [19] and Ramasamy et al. [20]. They concluded that the relationship between obesity and asthma is complex, involving biological and nonbiological factors, but they did not report a conclusive cause. Biological factors influencing asthma are immunity, inflammation, genetic factors, hormonal factors, sex, nutritional status, and physical activity. Nonbiological parameters are socioeconomic and educational status.

The immunological mechanism involving the proinflammatory state that is seen in almost all obese persons may link obesity with asthma. The proinflammatory state involves activated CD4+ Th2 release, interleukins IL-4, IL-5, and IL-13, mast cells degranulation, and release of mediators such as leukotrienes, prostaglandins, and several proinflammatory cytokines (tumor necrosis factor-α, IL-1, IL-6) causing bronchial spasms and increased mucus production [21].

In this study vitamin D supplementation to patients with bronchial asthma [at a dose of 2000 IU (50 mg) daily] for 3 months caused significant increase in the serum levels of vitamin D when compared with the corresponding values in group I, and was nearly similar to that of the control group, concluding an inverse relationship between vitamin D level and bronchial asthma severity.

These results were in agreement with those of Zwart et al. [12], who reported that vitamin D supplements were effective in increasing serum vitamin D levels. Furthermore, they prove the role of vitamin D status in stress and immune response. Several mechanisms have been postulated to explain how vitamin D modulates the pathogenesis of asthma.

Vitamin D may protect persons from developing respiratory infections that could aggravate asthma. It modulates the function of many immune cells including monocytes, macrophages, lymphocytes, and epithelial cells [22].

Lange et al. [23] stated that vitamin D inhibits the function of T lymphocytes both directly and through effects on antigen presenting cells. It has potent antiproliferative effects on CD4+ T cells. Essentially all published studies report the inhibition of Th1-associated cytokine production. Tang et al. [24] postulate that vitamin D promotes inhibition of Th2 responses. Th2 cells play a central role in the pathogenesis of asthma, producing cytokines such as IL-4, IL-5, and IL-13, and inducing the production of IgE by B cells, as well as the growth and differentiation of relevant effector cells, namely mast cells and eosinphils.

1, 25(OH)2D3 is mediated by the vitamin D receptor, which acts as a transcriptional regulator by binding to vitamin D-responsive elements target genes. It inhibits the nuclear factor-κB protein transcription factor expression in dendritic cells (DCs). DCs are instrumental in the generation of adaptive T-regulatory cells (Treg cells) through several mechanisms, including production of IL-10 or transforming growth factor-β [25].

Alyasin et al. [26] reported that vitamin D is involved in the maintenance of immune homeostasis. It has an important role in innate immunity, particularly through the direct induction of antimicrobial peptide (cathelicidin) gene expressions. Vitamin D may reverse the resistance to GCs in steroid-resistant asthma and potentiate the effect of allergen immunotherapy.

In this study vitamin D supplementation [at a dose of 2000 IU (50 mg) daily] for 3 months in patients with bronchial asthma caused significant increase in serum level of IL-10 when compared with the corresponding values in group I; the increased level was nearly similar to that of the control group, concluding a direct relationship between vitamin D level and IL-10.

These results were in agreement with Xystrakis et al. [27] and Maalmi et al. [28], who found that IL-10 regulates responses associated with allergic and asthmatic disease through its action upon CD4+ Th2 that acts on IL-4 and IL-13 and switch B cells to IgE synthesis. Also IL-5, which plays a role in eosinophil maturation and survival and IL-13, which regulates airway hyper-responsiveness and mucus hyperplasia. GCs and vitamin D also enhance IL-10 production through human CD4+ and CD8+ T cells. IL-10 is a potent anti-inflammatory and immunosuppressive cytokine that mediates its major immunosuppressive function by inhibiting antigen presenting cell function and cytokine production by macrophages and DCs, leading to profound inhibition of Th1 cell-mediated immunity, including inhibition of cytokine production by Th2 cells as well as mast cell and eosinophil function. There appears to be an inverse correlation between IL-10 levels and the incidence and/or severity of asthmatic and allergic disease.

Vitamin D signaling mediates the downregulation of immune reactions through two independent pathways: by upregulation of IL-10 expression and by control of the immunoglobulin production through upregulation of apoptosis of plasmablasts/plasma cells [29].

Xystrakis et al. [27] reported that supplementation with vitamin D enhanced GC-induced expression of IL-10 by Treg cells, and in subjects with steroid-resistant asthma vitamin D3 reversed ligand-induced downregulation of the GC receptor.

In this study vitamin D supplementation [at a dose of 2000 IU (50 mg) daily] for 3 months in patients with bronchial asthma caused significant improvement in FEV1, FVC, and FEV1/FVC when compared with the corresponding values in the group with bronchial asthma–classic regimen-treated group., The increased level was nearly similar to that of the control group.

These results were in agreement with those of Arshi et al. [30], who hypothesized that vitamin D has some roles in innate and adaptive immunity, inflammation reduction, and remodeling; therefore, it is supposed to affect the asthma phenotype, severity, and response to inhaled corticosteroid. A positive correlation was found between 25(OH)D levels and FEV1% in the studied asthmatic patients in this study.

In addition to affecting immune cells, vitamin D affects smooth muscle function and proliferation, which has a direct relevance on lung function in asthma and in airway remodeling [31].

Damera et al. [32] reported that in patients with asthma, higher serum vitamin D concentrations were associated with higher FEV1%. They attributed this to the fact that vitamin D inhibits the formation of matrix metalloprotease as well as fibroblast proliferation, and influences collagen synthesis; these actions mean that vitamin D may influence tissue remodeling and probably pulmonary function.


  Conclusion Top


The present study demonstrates that the frequency of vitamin D deficiency is highest in patients with severe and uncontrolled asthma, and that vitamin D supplementation is associated with increased serum levels of IL-10, with an obvious impact on immunity. Increased serum vitamin D level is associated with improvement in FEV1 and clinical parameters of asthma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Korn S, Hübner M, Jung M, Blettner M, Buhl R. Severe and uncontrolled adult asthma is associated with vitamin D in sufficiency and deficiency. Repir Res 2013; 14:25.  Back to cited text no. 1
    
2.
Lozano R. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010, a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380:2095–2128.  Back to cited text no. 2
    
3.
Kumar V, Abbas ANJ, Aster F. Robbins and Cotran pathologic basis of disease. 8th ed. Philadelphia: Saunders; 2010. 688.  Back to cited text no. 3
    
4.
Fathea M, Mohamed I. Study on the use of impulse oscillometry in the evaluation of children with asthma. Menoufia Med J 2013; 26:151–158.  Back to cited text no. 4
    
5.
Bai TR, Knight DA. Structural changes in the airways in asthma: observations and consequences. Clin Sci 2005; 108:463–477.  Back to cited text no. 5
    
6.
Paul G, Brehm JM, Alcorn JF, Holguin F, Aujla SJ, Celedon JC. Vitamin D and asthma. Am J Respir Crit Care Med 2012; 185:124–132.  Back to cited text no. 6
    
7.
Brehm JM, Schuemann B, Fuhlbrigge AL, Hollis BW, Strunk RC, Zeiger RS, et al. Serum vitamin D levels and severe asthma exacerbations in the childhood asthma management program study. J Allergy Clin Immunol 2010; 126:52–58.  Back to cited text no. 7
    
8.
Ginde AA, Mansbach JM, Camargo CA. Vitamin D, respiratory infections, and asthma. Curr Allergy Asthma Rep 2009; 9:81–87.  Back to cited text no. 8
    
9.
Hawrylowicz CM, O'Garra AI. Potential role of interleukin-10-secreting regulatory Tcells in allergy and asthma. Nat Rev Immunol 2005; 5:271–283.  Back to cited text no. 9
    
10.
Wu AC, Tantisira K, Li L, Fuhlbrigge AL, Weiss ST, Litonjua A. The effect of vitamin D and inhaled corticosteroid treatment on lung function in children. Am J Respir Crit Care Med 2012; 186:508–513.  Back to cited text no. 10
    
11.
American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Am Rev Respir Dis 1987; 136:225–235.  Back to cited text no. 11
    
12.
Zwart S, Mehta SK, Ploutz-Snyder R, Bourbeau VY, Locke J. Response to vitamin D supplementation during antarctic winter is related to BMI, and supplementation can mitigate Epstein-Barr virus reactivation1–3. J Nutr Nutr Immunol 2011; 110:13474.  Back to cited text no. 12
    
13.
Westergren A. Determination of erythrocyte sedimentation rate. Ann Med 1924; 26:577.  Back to cited text no. 13
    
14.
Pellegrino R, Viegi G, Brusasco V. Interpretive strategies for lung function tests. Eur Respir J 2005; 26:948–968.  Back to cited text no. 14
    
15.
Litonjua A, Weiss S. Is vitamin D deficiency to blame for the asthma epidemic? J Allergy Clin Immunol 2007; 120:1031–1035.  Back to cited text no. 15
    
16.
Li F, Peng M, Jiang L, Sun Q, Zhang K, Lian F, et al. Vitamin D deficiency is associated with decreased lung function in Chinese adults with asthma. Respiration 2010; 81:469–475.  Back to cited text no. 16
    
17.
Amelink M, de Nijs SB, de Groot JC, van Tilburg PM, van Spiegel PI, Krouwels FH, et al. Three phenotypes of adult-onset asthma. Allergy 2013; 68:674–680.  Back to cited text no. 17
    
18.
Kynyk J, Mastronarde J, McCallister J. Asthma, the sex difference. Curr Opin Pulm Med 2011; 17:6–11.  Back to cited text no. 18
    
19.
Ciprandi G, Brambilla I, Tosca MA, Arrigo T, Salpietro A, Leonardi S, et al. Body mass index is related with bronchial function and reversibility in children with allergic rhinitis and asthma. Int J Immunopathol Pharmacol 2011; 24:21–24.  Back to cited text no. 19
    
20.
Ramasamy A, Gupta N, Kumar R. Impact of obesity on bronchial asthma in Indian population. Lung India 2014; 31:121–126.  Back to cited text no. 20
    
21.
Bergmann K, Sypniewska G. Is there an association of allergy and cardiovascular disease. Biochem Med 2011; 21:210–218.  Back to cited text no. 21
    
22.
Yadav M, Mittal K. Effect of vitamin D supplementation on moderate to severe bronchial asthma. Indian J Pediatr 2014; 81:650–654.  Back to cited text no. 22
    
23.
Lange N, Litonjua A, Catherine M, Hawrylowicz C, Weiss S. Vitamin D, the immune system and asthma. Expert Rev Clin Immunol 2009; 5:693–702.  Back to cited text no. 23
    
24.
Tang J, Zhou R, Luger D. Calcitriol suppresses anti retinal autoimmunity through inhibitory effects on the Th17 effector response. J Immunol 2009; 182:4624–4632.  Back to cited text no. 24
    
25.
Taher Y, van Esch B, Hofman G, Henricks P, Oosterhout B. 1α,25-dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-β. J Immunol 2008; 180:5211–5221.  Back to cited text no. 25
    
26.
Alyasin S, Momen T, Kashef S, Alipour A, Amin R. The relationship between serum 25 hydroxy vitamin D levels and asthma in children. Allergy Asthma Immunol Res 2011; 3:251–255.  Back to cited text no. 26
    
27.
Xystrakis E, Kusumakar S, Boswell S, Peek E, Urry Z, Richards DF, et al. Reversing the defective induction of IL-10–secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest 2006; 116:146–155.  Back to cited text no. 27
    
28.
Maalmi H, Berraies A, Tangour E, Ammar J, Abid H. The impact of vitamin D deficiency on immune T cells in asthmatic children: a case–control study. J Asthma Allergy 2012; 5:11–19.  Back to cited text no. 28
    
29.
Heine G, Anton K, Henz BM, Worm M. 1alpha, 25-dihydroxyvitaminD3 inhibits anti-CD40 plus IL-4-mediated IgE production in vitro Eur. J Immunol 2002; 32:3395–3404.  Back to cited text no. 29
    
30.
Arshi S, Fallahpour M, Nabavi M, Bemanian MH, Javad-Mousavi SA, Nojomi M, et al. The effects of vitamin D supplementation on airway functions in mild to moderate persistent asthma. Ann Allergy Asthma Immunol 2014; 113:404–409.  Back to cited text no. 30
    
31.
Sakurai R, Shin E, Fonseca S. Sakurai T, Litonjua AA, Weiss ST. 1α,25(OH)2D3 and its 3-epimer promote rat lung alveolar epithelial-mesenchymal interactions and inhibit lipo fibroblast apoptosis. Am J Physiol Lung Cell Mol Physiol 2009; 297:496–505.  Back to cited text no. 31
    
32.
Damera G, Fogle HW, Lim P, Goncharova EA, Zhao H, Banerjee A. Vitamin D inhibits growth of human smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1. Br J Pharmacol 2009; 158:1429–1441.  Back to cited text no. 32
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed607    
    Printed0    
    Emailed0    
    PDF Downloaded56    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]