|Year : 2023 | Volume
| Issue : 2 | Page : 51-55
Vitamin D levels in children with allergic rhinitis and asthma in South India: A cross-sectional study
Jesin Kumar Chakkamadathil1, Sanjeev Nair2, Ravindran Chetambath3
1 Department of Pulmonary Medicine, Karuna Medical College, Palakkad, Kerala, India
2 Department of Pulmonary Medicine, Government Medical College, Thrissur, Kerala, India
3 Department of Pulmonary Medicine, Baby Memorial Hospital, Kozhikode, Kerala, India
|Date of Submission||05-Jun-2022|
|Date of Acceptance||07-Jul-2022|
|Date of Web Publication||02-May-2023|
Dr. Jesin Kumar Chakkamadathil
Shivam, Guruvayur Road, Punkunnam, Thrissur - 680 002, Kerala
Source of Support: None, Conflict of Interest: None
Background: Vitamin D deficiency has been declared a public health problem for both adults and children worldwide. Asthma and related allergic disorders are leading causes of morbidity in children. The objective of this study was to estimate Vitamin D levels in children suffering from asthma and allergic rhinitis in North Kerala. Objectives: (1) To evaluate Vitamin D levels among children between the age group 5 and 18 years suffering from asthma and/or allergic rhinitis. (2) To study the factors associated with low levels of Vitamin D and (3) to study the correlation between Vitamin D levels, immunoglobulin E (IgE), and absolute eosinophil count (AEC). Materials and Methods: This is a retrospective analysis of hospital data in which data of children between the age group 5 and 18 years attending the pulmonology outpatient department of a tertiary care hospital in North Kerala are captured. The study period was 6 months from March 01, 2021, to August 31, 2021. Detailed clinical history, physical examination, and laboratory investigations including complete blood cell count, IgE, and 25 dihydroxyvitamin D3 (Vitamin D) level were done. Diagnosis of allergic rhinitis and asthma is made on the clinical presentation by an experienced pulmonologist. Family history of asthma or allergic rhinitis was also recorded. Data were entered into Microsoft Excel, and analysis was done using Epi Info 7. Means and standard deviation were calculated, and correlation was assessed between Vitamin D levels, IgE, AEC, and age of the children. Results: Thirty percent of children in the study group had Vitamin D deficiency, 56% had insufficient values, and 14% had normal values. Most of the children with low Vitamin D levels had raised values for IgE and AEC, but the association was not statistically significant. Conclusion: Most of the children in this part of the state presenting with respiratory allergy have low or insufficient levels of Vitamin D. This may be one of the reasons for poor control of symptoms and such children may require Vitamin D supplementation along with optimal treatment of respiratory allergy.
Keywords: Allergy, asthma, immunoglobulin E, Vitamin D
|How to cite this article:|
Chakkamadathil JK, Nair S, Chetambath R. Vitamin D levels in children with allergic rhinitis and asthma in South India: A cross-sectional study. J Adv Lung Health 2023;3:51-5
|How to cite this URL:|
Chakkamadathil JK, Nair S, Chetambath R. Vitamin D levels in children with allergic rhinitis and asthma in South India: A cross-sectional study. J Adv Lung Health [serial online] 2023 [cited 2023 May 28];3:51-5. Available from: https://www.jalh.org//text.asp?2023/3/2/51/375531
| Introduction|| |
Allergic rhinitis and asthma are common diseases in childhood. Asthma is the 13th leading cause of death in India. Many children are brought with uncontrolled asthma due to frequent respiratory viral infections. It has been hypothesized that low Vitamin D levels may be responsible for the increasing prevalence of asthma and allergic rhinitis worldwide. Various studies from across the globe have reported a high prevalence of Vitamin D deficiency in children with asthma and allergic diseases., Vitamin D deficiency has been reported in many subgroups including healthy children, young adults (especially African Americans), and middle-aged and elderly individuals., However, the levels of Vitamin D in Indian children with allergic rhinitis and asthma have not been documented. Analysis of the third National Health and Nutrition Examination Survey data reported that patients with asthma and Vitamin D deficiency (25[OH] Vitamin D <10 μg/L) had higher rates of recurrent upper respiratory tract infections compared to those with serum 25(OH) Vitamin D levels >30 μg/L (59 vs. 22%; P < 0.001). Vitamin D levels during pregnancy have also been postulated to play an important role in the development of asthma and allergy in children. This is due to the effects of Vitamin D on the developing lung and immune system during the fetal and early neonatal periods. It has been reported that higher maternal dietary Vitamin D intake during pregnancy conferred various protective effects on wheezing phenotypes in young children in two separate cohorts, with over 60% reduction in recurrent wheezing in young children born to mothers with higher intake of Vitamin D.
The prevalence of Vitamin D deficiency has been increasing in the general population in recent decades. This high prevalence of Vitamin D deficiency has been attributed to the avoidance of sun exposure, indoor lifestyle, use of sunscreen, and decreased intake of Vitamin D-containing foods. Since Vitamin D is sequestered in adipose tissue, the increasing prevalence of obesity can also explain the higher prevalence of Vitamin D deficiency. Several other cross-sectional studies conducted in adults and children have found that Vitamin D deficiency was associated with allergic nasal symptoms, wheezing, lower lung function, and poor asthma control. It has also been noted that the cutoff values for deficiency and insufficiency of Vitamin D among individuals are not uniform worldwide. If we consider <20 ng/mL for deficiency and 20–30 ng/mL for insufficiency, most of the individuals in this part of the state would have low values of Vitamin D. This was the subject of study in major centers of the country and they have come out with a new set of values in tropics for deficiency, insufficiency, and normalcy. This cross-sectional study is an attempt to study the correlation between Vitamin D levels among children aged 5–18 years with asthma and allergic rhinitis.
- To evaluate Vitamin D levels among children aged 5–18 years suffering from asthma and/or allergic rhinitis
- To study the factors associated with low levels of Vitamin D in this cohort
- To study the correlation between Vitamin D level with immunoglobulin E (IgE) and absolute eosinophil count (ACE).
| Materials and Methods|| |
The study was conducted in the pulmonology department of a tertiary care hospital in North Kerala.
Period of study
The study was conducted among patients attending the outpatient clinic for 6 months from March 01, 2021, to August 31, 2021.
This was a clinic-based cross-sectional study done in a tertiary care hospital in North Kerala. All children presenting with asthma and/or allergic rhinitis were included in the study. A census sampling was done and all children presenting to the outpatient department with a pulmonologist's diagnosis of allergic rhinitis and/or asthma were included in the study. Vitamin D levels, serum IgE levels, and AEC were measured for all the children. Data were entered into Microsoft Excel, and analysis was done using Epi Info 7 (Division of Health Informatics & Surveillance (DHIS) Center for Surveillance, Epidemiology & Laboratory Services (CSELS) U.S. Department of Health & Human Services Centres for disease control and prevention 1600 Clifton Road Atlanta, GA 30329-4027 USA). Mean and standard deviation were calculated and any correlation between Vitamin D levels, IgE, AEC, and age of the children were analyzed. Children were considered deficient for Vitamin D if the serum level was <12 ng/mL; insufficient if it was between 12 and 20 ng/mL and normal if it was between 20 and 50 ng/mL. Serum IgE levels >140 IU/ml and AEC >440 cells/mm3 were considered abnormal.
Children aged between 5 and 18 years suffering from allergic rhinitis and/or asthma.
- Children with florid clinical findings of rickets or children having bony abnormalities such as kyphoscoliosis, pectus excavatum, pectus carinatum, or bow legs
- Children of parents who did not sign a written consent.
The study was approved by the institutional ethics committee.
| Results|| |
The study included 50 children between the ages of 5 and 18 years. The mean age of the children was 11.62 years and 23 (46%) of the children were males. The general characteristics of the study population are given in [Table 1]a and [Table 1]b.
Vitamin D levels were measured for all the children. The mean Vitamin D was 15.11 with a standard deviation of 5.1 and the median Vitamin D was 14.6 (interquartile range [IQR] of 11.6–18.8). The study subjects were categorized as deficient, insufficient, or normal using cutoff values of 12 and 20, respectively. The proportions are as in [Table 2].
The factors associated with low Vitamin D levels were studied. The results are shown in [Table 3].
Only the female sex was statistically correlated with low Vitamin D levels.
We also looked for a correlation between the Vitamin D on one hand and the IgE and AEC on the other hand. Most of the children with low Vitamin D levels had raised values for IgE and AEC. However, there was a poor statistical correlation for Vitamin D with serum IgE and AEC. The results are shown in [Figure 1] and [Figure 2].
|Figure 2: Correlation between Vitamin D and AEC. AEC: Absolute eosinophil count|
Click here to view
| Discussion|| |
Vitamin D insufficiency appears to play an important in a wide range of pulmonary diseases including viral and bacterial respiratory infections, asthma, chronic obstructive pulmonary disease (COPD), and cancer. Vitamin D deficiency is prevalent worldwide and may partly explain the recent increase in asthma and allergic diseases that have occurred over the past 50–60 years. The role of Vitamin D in mediating innate immune responses through the production of antimicrobial peptides and autophagy; and in adaptive immune responses through the promotion of regulatory lymphocytes; is believed to underpin these associations. The principal source of Vitamin D is sunlight; solar ultraviolet B radiation converts 7-dehydrocholesterol in the skin to pre-Vitamin D3. Our environment, lifestyle, and our genes greatly influence the efficacy of this pathway. Dietary intake of Vitamin D is limited. Asthma, COPD, interstitial lung disease, and cystic fibrosis show correlations between severity and low Vitamin D status, as is also seen in pulmonary infections and lung cancer. Polymorphisms in the Vitamin D receptor gene are associated with lower respiratory tract infections and severe respiratory syncytial virus bronchiolitis in children. In addition, levels and polymorphisms of Vitamin D binding protein are associated with COPD. Vitamin D can inhibit the proliferation of airway smooth muscle and many pathways implicated in airway remodeling, such as matrix metalloproteases. Vitamin D reduces the expression of costimulatory molecules that are necessary for positive T-cell receptor signaling, and pro-inflammatory cytokines. Vitamin D also regulates adaptive lymphocyte responses, inhibiting lymphocyte proliferation and cytokine production in pro-inflammatory T helper 1 (Th1) and Th17 responses. Vitamin D may potentially decrease the severity of asthma and allergies through a variety of mechanisms including effects on immune cells, improved handling or prevention of predisposing infections, decreased inflammatory responses, improved lung function, effects on airway smooth muscle function and mass, reduced airway remodeling and reversal of steroid resistance (by interleukin production and modifying ligand-induced downregulation of glucocorticoid receptors). A cross-sectional study done on 616 asthmatic Costa Rican children found that higher serum Vitamin D concentrations were associated with a reduction in the need for anti-inflammatory medications and hospitalization during the previous year. However, several studies from other countries have demonstrated mixed results in the association of Vitamin D deficiency and asthma. In children, a Vitamin D-deficient diet was associated with a decreased response to bronchodilators, increased incidence of allergic rhinitis, and increased incidence of asthma. Other studies have found that maternal diets poor in Vitamin D led to an increased risk of reactive airways in the offspring. Research is now moving into large intervention studies examining the role of patient supplementation of Vitamin D to treat diseases and also maternal/early life supplementation to prevent the development of pulmonary diseases. Vitamin D Antenatal Asthma Reduction Trial is investigating whether maternal supplementation in pregnancy may reduce the incidence of asthma and allergic illnesses.
This study evaluated children with allergic rhinitis and asthma to know the level of Vitamin D and its correlation between variables such as IgE and AEC. Among the study participants, 56% were females, 82% were between 5 and 15 years, and 18% were between 16 and 18 years. Allergic rhinitis constituted 48% and asthma constituted 38%. Fourteen percent had combined allergic rhinitis and asthma. Among these children, 15 (30%) had a deficient level, 28 (56%) had an insufficient level, and only 14% had normal levels of Vitamin D. The prevalence of severe Vitamin D deficiency was significantly higher in Qatari children with asthma (17%), allergic rhinitis (18.5%), and wheezing (23.4%) than in healthy children (10.5%), which is in agreement with the studies conducted among African-American and Iranian children. A few epidemiological studies have reported a similar finding that Vitamin D deficiency is associated with an increased incidence of asthma and allergy symptoms.
Many centers in India have reported a high prevalence of Vitamin D deficiency. This was more so in northern India and in some parts of southern India. There is controversy over what levels are optimal for overall health. Serum level of Vitamin D between 30 and 40 ng/mL (75–100 nmol/L) has been suggested as a lower threshold of an optimal serum level for the immune effects of Vitamin D. However, a study conducted by Vijayakumar et al. demonstrated that only 11.1% of children in Kerala had Vitamin D deficiency. This could be since the authors have used a lower cutoff value for deficiency (<12 ng/mL) and insufficiency (12–20 ng/mL). The study also reported that children with respiratory allergies were more likely to be deficient compared to healthy children. In our study, we used the same cutoff values as Vijayakumar et al. to evaluate the children. In the study, the sample of Qatari children, nearly half of the healthy children also had mild Vitamin D deficiency (48.6%) and 10.5% had severe deficiency. This indicates that the incidence of Vitamin D insufficiency is surprisingly high in the general population.
In addition, Vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. Searing et al. in a cross-sectional study of 100 asthmatic children showed that Vitamin D levels were inversely associated with serum IgE, the number of skin prick tests positive for perennial aeroallergens, lung function, and use of inhaled or oral corticosteroids. We have also noticed that children with allergic diseases have higher values for IgE (Mean 1746, IQR-950–1912) and AEC (Mean 642, IQR-400–660) even though they were not statistically significant. Several clinical, genetic, and experimental studies suggest that prior history of atopic dermatitis (AD) and its severity are major risk factors for the development of allergic rhinitis, asthma, and specific sensitization. This highlights the importance of the epidermal barrier in the pathogenesis of these allergic disorders. Low levels of Vitamin D also appear to inversely correlate with AD severity, and Vitamin D deficiency at birth is associated with a higher risk of developing AD. Furthermore, a pilot randomized trial of Vitamin D supplementation in children demonstrated a favorable effect on AD symptoms during winter months. Vitamin D levels <15 ng/mL were associated with evidence of sensitization to various allergens. For example, the odds ratio of allergy for peanut, ragweed, and oak were 2.39, 1.83, and 4.75, respectively.
The risk factors associated with lower levels of Vitamin D in our study population were the higher age group (16–18 years), female sex, combined allergy, and atopic status. However, association with female sex was the only one found to be statistically significant.
| Conclusion|| |
This study showed that Vitamin D levels were deficient or insufficient in the majority of children suffering from allergic rhinitis and asthma. Vitamin D levels are inversely related to serum IgE levels and AECs, even though this association was not statistically significant. The role of Vitamin D in maintaining overall health and what values represent adequate levels of Vitamin D in the blood for human health generally are still not well defined. This remains true for allergic rhinitis and asthma too. Although many studies have suggested the benefit of raising Vitamin D levels, more studies are needed in this field. Hence, clinical trials investigating the role of Vitamin D in modifying the severity of asthma and allergies and in controlling exacerbations need to be undertaken.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Majak P, Olszowiec-Chlebna M, Smejda K, Stelmach I. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol 2011;127:1294-6.
Weiss ST, Litonjua AA. Childhood asthma is a fat-soluble vitamin deficiency disease. Clin Exp Allergy 2008;38:385-7.
Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006;81:353-73.
Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, et al
. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr 2002;76:187-92.
Camargo JC, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST, Gold DR, et al
. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at age 3 years. Am J Clin Nutr 2007;85:788-95.
Devereux G, Litonjua AA, Turner SW, Craig LC, McNeill G, Martindale S, et al
. Maternal vitamin D intake during pregnancy and early childhood wheezing. Am J Clin Nutr 2007;85:853-9.
Bener A, Ehlayel MS, Bener HZ, Hamid Q. The impact of Vitamin D deficiency on asthma, allergic rhinitis and wheezing in children: An emerging public health problem. J Family Community Med 2014;21:154-61.
Vijayakumar M, Bhatia V, George B. Vitamin D status of children in Kerala, southern India. Public Health Nutr 2020;23:1179-83.
Mirzakhani H, Al-Garawi A, Weiss ST, Litonjua AA. Vitamin D and the development of allergic disease: How important is it? Clin Exp Allergy 2015;45:114-25.
Hossein-nezhad A, Holick MF. Vitamin D for health: A global perspective. Mayo Clin Proc 2013;88:720-55.
Litonjua AA, Lange NE, Carey VJ, Brown S, Laranjo N, O'Connor GT, et al
. The Vitamin D Antenatal Asthma Reduction Trial (VDAART): Rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children. Contemp Clin Trials 2014;38:37-50.
Freishtat RJ, Iqbal SF, Pillai DK, Klein CJ, Ryan LM, Benton AS, et al
. High prevalence of vitamin D deficiency among inner-city African American youth with asthma in Washington, DC. J Pediatr 2010;156:948-52.
Alyasin S, Momen T, Kashef S, Alipour A, Amin R. The relationship between serum 25 hydroxyvitamin D levels and asthma in children. Allergy Asthma Immunol Res 2011;3:251-5.
Litonjua AA. Childhood asthma may be a consequence of vitamin D deficiency. Curr Opin Allergy Clin Immunol 2009;9:202-7.
Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.
Brehm JM, Celedón JC, Soto-Quiros ME, Avila L, Hunninghake GM, Forno E, et al
. Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med 2009;179:765-71.
Searing DA, Zhang Y, Murphy JR, Hauk PJ, Goleva E, Leung DY. Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use. J Allergy Clin Immunol 2010;125:995-1000.
Zheng T, Yu J, Oh MH, Zhu Z. The atopic march: Progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res 2011;3:67-73.
Sidbury R, Sullivan AF, Thadhani RI, Camargo CA Jr. Randomized controlled trial of vitamin D supplementation for winter-related atopic dermatitis in Boston: A pilot study. Br J Dermatol 2008;159:245-7.
Sharief S, Jariwala S, Kumar J, Muntner P, Melamed ML. Vitamin D levels and food and environmental allergies in the United States: Results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol 2011;127:1195-202.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]