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Asthma and vitamin D in Brazilian adolescents: Study of Cardiovascular Risks in Adolescents (ERICA)

ABSTRACT

Objective:

To evaluate the association between asthma prevalence and serum levels of vitamin D in Brazilian adolescents.

Methods:

This was a cross-sectional, school-based study involving adolescents between 12-17 years of age from four large Brazilian cities located at different latitudes (Fortaleza, Rio de Janeiro, Brasília, and Porto Alegre). Information on asthma diagnosis, lifestyle, and sociodemographic characteristics was collected by means of self-administered questionnaires. Serum concentrations of calcifediol were dichotomized as sufficient (≥ 20 ng/mL) or insufficient/deficient (< 20 ng/mL) levels. Bivariate analyses were carried out between vitamin D levels and prevalence of active asthma (AA), as well as other variables in study, using the chi-square test. Generalized linear models were configured to analyze potential confounding factors (p < 0.20).

Results:

Between 2013 and 2014, 1,053 adolescents were evaluated. The prevalences of AA and insufficient/deficient levels of calcifediol were 15.4% and 21%, respectively. There were no statistically significant associations between AA and hypovitaminosis D. The prevalences of AA and vitamin D insufficiency were, respectively, 2.34 (95% CI, 1,28-4.30) and 3.22 (95% CI, 1.75-5.95) times higher in Porto Alegre than in Rio de Janeiro, regardless of possible confounding factors. However, no significant associations were found between the prevalence of AA and vitamin-D-related variables in any of the cities.

Conclusions:

No association was found between AA and low levels of vitamin D in adolescents living at different latitudes in Brazil.

Keywords:
Adolescent; Asthma/epidemiology; Vitamin D

RESUMO

Objetivo:

Avaliar a associação entre a prevalência de asma e níveis séricos de vitamina D em adolescentes brasileiros.

Métodos:

Estudo transversal de base escolar com adolescentes de 12 a 17 anos provenientes de quatro grandes cidades brasileiras em diferentes latitudes (Fortaleza, Rio de Janeiro, Brasília e Porto Alegre). Informações sobre o diagnóstico de asma, estilo de vida e características sociodemográficas foram coletadas por meio de questionários autoaplicáveis. As concentrações séricas de calcifediol foram dicotomizadas: suficientes (≥ 20 ng/mL) e insuficientes/deficientes (< 20 ng/mL). Foram realizadas análises bivariadas entre os níveis de vitamina D e a prevalência de asma ativa (AA), além de outras variáveis, por meio do teste do qui-quadrado. Modelos lineares generalizados foram configurados para analisar possíveis fatores de confusão (p < 0,20).

Resultados:

Entre 2013 e 2014, foram avaliados 1.053 adolescentes. A prevalência de AA e níveis insuficientes/deficientes de calcifediol foram de 15,4% e 21%, respectivamente. Não houve associações estatisticamente significativas entre AA e hipovitaminose D. As prevalências de AA e insuficiência de vitamina D foram, respectivamente, 2,34 (IC95%: 1,28-4,30) e 3,22 (IC95%: 1,75-5,95) vezes maiores em Porto Alegre que no Rio de Janeiro, independentemente de possíveis fatores de confusão. No entanto, não foram observadas associações significativas entre a prevalência de AA e variáveis relacionadas à vitamina D em nenhuma das cidades.

Conclusões:

Não se observou nenhuma associação entre AA e níveis baixos de vitamina D em adolescentes residentes em diferentes latitudes no Brasil.

Descritores:
Adolescente; Asma/epidemiologia; Vitamina D

INTRODUCTION

Asthma is a heterogeneous disease with several clinical phenotypes, being characterized by chronic inflammation of the lower airways. It is a global health problem with an increasing prevalence in recent decades.11 Global Initiative for Asthma (GINA) [homepage on the Internet]. Bethesda: GINA; c2021 [cited 2021 Jul 1]. Global Strategy for Asthma Management and Prevention (Updated 2021). [Adobe Acrobat document, 217p.]. Available from: https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf
https://ginasthma.org/wp-content/uploads...
) According to the International Study of Asthma and Allergies in Childhood (ISAAC), the mean prevalence of asthma in Brazil in 2006 was 24.3% and 19.0% in children between 6 and 7 years of age and in adolescents, respectively, causing a significant burden on the health care system and the quality of life of patients and their families.22 Solé D, Wandalsen GF, Camelo-Nunes IC, Naspitz CK; ISAAC - Brazilian Group. Prevalence of symptoms of asthma, rhinitis, and atopic eczema among Brazilian children and adolescents identified by the International Study of Asthma and Allergies in Childhood (ISAAC) - Phase 3. J Pediatr (Rio J). 2006;82(5):341-346. https://doi.org/10.2223/JPED.1521
https://doi.org/10.2223/JPED.1521...
) More recently, the Estudo de Riscos Cardiovasculares em Adolescentes (ERICA, Study of Cardiovascular Risks in Adolescents) revealed a prevalence of asthma of 13.1% in adolescents.33 Kuschnir FC, Gurgel RQ, Solé D, Costa E, Felix MM, de Oliveira CL, et al. ERICA: prevalence of asthma in Brazilian adolescents [published correction appears in Rev Saude Publica. 2016;50:13serr]. Rev Saude Publica. 2016;50 Suppl 1(Suppl 1):13s. https://doi.org/10.1590/s01518-8787.2016050006682
https://doi.org/10.1590/s01518-8787.2016...

The relationship between micronutrient deficiency and the etiology of asthma has been a subject of study in recent years.44 Checkley W, Robinson CL, Baumann LM, Hansel NN, Romero K, Pollard SL, et al. 25-hydroxy vitamin D levels are associated with childhood asthma in a population-based study in Peru. Clin Exp Allergy. 2015;45(1):273-282. https://doi.org/10.1111/cea.12311
https://doi.org/10.1111/cea.12311...
) Several studies have shown that vitamin D also participates in the pathogenesis of chronic, infectious, and autoimmune diseases.55 Lilani MZHA, Elahi RT, Ahmed A, Alam MM, Batool SS. Vitamin D supplementation: An innovative way to prevent asthma exacerbation in developing countries?. J Taibah Univ Med Sci. 2018;14(1):99-100. https://doi.org/10.1016/j.jtumed.2018.11.010
https://doi.org/10.1016/j.jtumed.2018.11...

6 Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008;8(9):685-698. https://doi.org/10.1038/nri2378
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-77 Castro LC. The vitamin D endocrine system [Article in Portuguese]. Arq Bras Endocrinol Metabol. 2011;55(8):566-575. https://doi.org/10.1590/S0004-27302011000800010
https://doi.org/10.1590/S0004-2730201100...
) There is an increasing number of studies pointing to a protective role of vitamin D and correlating its circulating levels with the severity and control of asthma.55 Lilani MZHA, Elahi RT, Ahmed A, Alam MM, Batool SS. Vitamin D supplementation: An innovative way to prevent asthma exacerbation in developing countries?. J Taibah Univ Med Sci. 2018;14(1):99-100. https://doi.org/10.1016/j.jtumed.2018.11.010
https://doi.org/10.1016/j.jtumed.2018.11...
,66 Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008;8(9):685-698. https://doi.org/10.1038/nri2378
https://doi.org/10.1038/nri2378...
) However, the lack of consensus does not allow the general recommendation of using vitamin D as a supplement in asthma patients.88 Litonjua AA. Vitamin D deficiency as a risk factor for childhood allergic disease and asthma. Curr Opin Allergy Clin Immunol. 2012;12(2):179-185. https://doi.org/10.1097/ACI.0b013e3283507927
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,99 Shaheen SO. Vitamin D deficiency and the asthma epidemic. Thorax. 2008;63(3):293. https://doi.org/10.1136/thx.2007.091728
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Vitamin D deficiency is also considered a global public health problem, and its increased prevalence is closely related to changes in lifestyle, such as lack of exposure to sunlight, reduced intake of food sources of vitamin D, overweight/obesity, more indoor activities, and daily use of sunscreen. Low serum levels of vitamin D have been suggested to have a negative influence on lung function, number of exacerbations, and response to inhaled corticosteroids.55 Lilani MZHA, Elahi RT, Ahmed A, Alam MM, Batool SS. Vitamin D supplementation: An innovative way to prevent asthma exacerbation in developing countries?. J Taibah Univ Med Sci. 2018;14(1):99-100. https://doi.org/10.1016/j.jtumed.2018.11.010
https://doi.org/10.1016/j.jtumed.2018.11...
,1010 Korn S, Hübner M, Jung M, Blettner M, Buhl R. Severe and uncontrolled adult asthma is associated with vitamin D insufficiency and deficiency. Respir Res. 2013;14(1):25. https://doi.org/10.1186/1465-9921-14-25
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,1111 Litonjua AA. Childhood asthma may be a consequence of vitamin D deficiency. Curr Opin Allergy Clin Immunol. 2009;9(3):202-207. https://doi.org/10.1097/ACI.0b013e32832b36cd
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) The aim of this study was to assess the association between asthma and serum vitamin D levels in adolescents in Brazil. Our hypothesis was that asthma might be more prevalent in adolescents with insufficient levels of this micronutrient.

METHODS

This study was an integral part of the ERICA project, a multicenter cross-sectional school-based study. The main objective of the ERICA was to estimate the prevalence of metabolic syndrome and cardiovascular risk factors in adolescents between 12 and 17 years of age, regardless of the sex, attending public or private schools in Brazilian cities with more than 100,000 inhabitants.1212 Bloch KV, Szklo M, Kuschnir MC, Abreu Gde A, Barufaldi LA, Klein CH, et al. The Study of Cardiovascular Risk in Adolescents--ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents [published correction appears in BMC Public Health. 2015;15:850]. BMC Public Health. 2015;15:94. The study population was stratified into 32 geographical strata (27 capitals, including the Federal District of Brasília, and 5 sets with other municipalities in each macroregion of the country). A sample of 1,251 schools in 124 Brazilian municipalities was selected with a probability proportional to the population size. In each of the selected schools three combinations of shifts and grades were selected; within each of these combinations, one classroom was selected. All eligible students in the selected classrooms were included in the study. The design sampling weights were calculated by the product of the reciprocals of the inclusion probabilities in each sampling stage and were later calibrated considering the projections of the numbers of adolescents enrolled in the schools located in the geographical strata by sex and age. A total of 74,589 adolescents were evaluated. The ERICA sample has proven to be nationally and regionally representative, as well as in relation to each capital involved. Details of the sampling process have been described elsewhere.1313 Vasconcellos MT, Silva PL, Szklo M, Kuschnir MC, Klein CH, Abreu Gde A, et al. Sampling design for the Study of Cardiovascular Risks in Adolescents (ERICA). Cad Saude Publica. 2015;31(5):921-930. https://doi.org/10.1590/0102-311X00043214
https://doi.org/10.1590/0102-311X0004321...

The sample of the present study was composed by a subsample of students who attended morning classes in 4 cities located at different latitudes: Fortaleza, Rio de Janeiro, Porto Alegre, and Brasília. Serum 25-hydroxyvitamin D levels were assessed.1212 Bloch KV, Szklo M, Kuschnir MC, Abreu Gde A, Barufaldi LA, Klein CH, et al. The Study of Cardiovascular Risk in Adolescents--ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents [published correction appears in BMC Public Health. 2015;15:850]. BMC Public Health. 2015;15:94.,1313 Vasconcellos MT, Silva PL, Szklo M, Kuschnir MC, Klein CH, Abreu Gde A, et al. Sampling design for the Study of Cardiovascular Risks in Adolescents (ERICA). Cad Saude Publica. 2015;31(5):921-930. https://doi.org/10.1590/0102-311X00043214
https://doi.org/10.1590/0102-311X0004321...
) The cities were selected because of their location and because their biorepositories were active during the study period. The participants were selected using proportional random allocation to ensure a thorough distribution of sex, age, skin color, season at data collection, and estimated sunlight exposure.1414 de Oliveira CL, Cureau FV, Cople-Rodrigues CDS, Giannini DT, Bloch KV, Kuschnir MCC, et al. Prevalence and factors associated with hypovitaminosis D in adolescents from a sunny country: Findings from the ERICA survey. J Steroid Biochem Mol Biol. 2020;199:105609. https://doi.org/10.1016/j.jsbmb.2020.105609
https://doi.org/10.1016/j.jsbmb.2020.105...

Data collection included information on sociodemographic characteristics, such as sex, age, skin color, type of school (public or private), physical activity, season at blood sampling, and latitude according to the location of each city. Anthropometric measurements were taken.1212 Bloch KV, Szklo M, Kuschnir MC, Abreu Gde A, Barufaldi LA, Klein CH, et al. The Study of Cardiovascular Risk in Adolescents--ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents [published correction appears in BMC Public Health. 2015;15:850]. BMC Public Health. 2015;15:94. Data were collected through a self-administered electronic questionnaire. The participants fasted for 12 h, and blood samples were collected at school, stored at −80°C, and subsequently analyzed at the same laboratory.1212 Bloch KV, Szklo M, Kuschnir MC, Abreu Gde A, Barufaldi LA, Klein CH, et al. The Study of Cardiovascular Risk in Adolescents--ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents [published correction appears in BMC Public Health. 2015;15:850]. BMC Public Health. 2015;15:94. Variables regarding asthma were extracted from the written standardized questionnaire of the International Study of Asthma and Allergies in Childhood asthma module for the 13-to 14-year-old age group. The questionnaire had previously been translated to Portuguese and validated for use in Brazil.1515 Solé D, Vanna AT, Yamada E, Rizzo MC, Naspitz CK. International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire: validation of the asthma component among Brazilian children. J Investig Allergol Clin Immunol. 1998;8(6):376-382.

Active asthma (AA) was defined as the occurrence of at least one asthma attack in the last 12 months.33 Kuschnir FC, Gurgel RQ, Solé D, Costa E, Felix MM, de Oliveira CL, et al. ERICA: prevalence of asthma in Brazilian adolescents [published correction appears in Rev Saude Publica. 2016;50:13serr]. Rev Saude Publica. 2016;50 Suppl 1(Suppl 1):13s. https://doi.org/10.1590/s01518-8787.2016050006682
https://doi.org/10.1590/s01518-8787.2016...
) The other variables were categorized as follows: age range (12-14 years and 15-17 years); self-reported skin color (white, black, brown, yellow, or indigenous)1616 Brasil. Instituto Brasileiro de Geografia e Estatística (IBGE) [homepage on the Internet]. Rio de Janeiro: IBGE; [cited 2021 Feb 26. Comissão Nacional de Classificação (CONCLA). Available from: https://cnae.ibge.gov.br
https://cnae.ibge.gov.br...
) and categorized as “White” or “non-White”; type of school (public or private), and screen time (< or ≥ 2 h/day). The period of data collection was categorized according to the seasons (fall, winter, spring, or summer). Nutritional status and physical activity were also evaluated.1414 de Oliveira CL, Cureau FV, Cople-Rodrigues CDS, Giannini DT, Bloch KV, Kuschnir MCC, et al. Prevalence and factors associated with hypovitaminosis D in adolescents from a sunny country: Findings from the ERICA survey. J Steroid Biochem Mol Biol. 2020;199:105609. https://doi.org/10.1016/j.jsbmb.2020.105609
https://doi.org/10.1016/j.jsbmb.2020.105...
,1717 Cureau FV, da Silva TL, Bloch KV, Fujimori E, Belfort DR, de Carvalho KM, et al. ERICA: leisure-time physical inactivity in Brazilian adolescents. Rev Saude Publica. 2016;50 Suppl 1(Suppl 1):4s. https://doi.org/10.1590/s01518-8787.2016050006683
https://doi.org/10.1590/s01518-8787.2016...
,1818 Souza Ade M, Barufaldi LA, Abreu Gde A, Giannini DT, de Oliveira CL, dos Santos MM, et al. ERICA: intake of macro and micronutrients of Brazilian adolescents. Rev Saude Publica. 2016;50 Suppl 1(Suppl 1):5s. https://doi.org/10.1590/s01518-8787.2016050006698
https://doi.org/10.1590/s01518-8787.2016...
Physical activity was assessed using an adapted version of the self-administered Physical Activity Checklist, previously validated for Brazilian adolescents.1717 Cureau FV, da Silva TL, Bloch KV, Fujimori E, Belfort DR, de Carvalho KM, et al. ERICA: leisure-time physical inactivity in Brazilian adolescents. Rev Saude Publica. 2016;50 Suppl 1(Suppl 1):4s. https://doi.org/10.1590/s01518-8787.2016050006683
https://doi.org/10.1590/s01518-8787.2016...
Participants performing ≥ 300 min/week of physical activity were classified as physically active.1717 Cureau FV, da Silva TL, Bloch KV, Fujimori E, Belfort DR, de Carvalho KM, et al. ERICA: leisure-time physical inactivity in Brazilian adolescents. Rev Saude Publica. 2016;50 Suppl 1(Suppl 1):4s. https://doi.org/10.1590/s01518-8787.2016050006683
https://doi.org/10.1590/s01518-8787.2016...
) Anthropometric measurements were performed with participants placed in a standing position, barefoot, and wearing light clothing, by means of an electronic scale (model P200M; Líder, São Paulo, Brazil) with a capacity of up to 200 kg (precision, 50 g) and a portable stadiometer (Alturaexata, Minas Gerais, Brazil; precision, 0.1 cm).1212 Bloch KV, Szklo M, Kuschnir MC, Abreu Gde A, Barufaldi LA, Klein CH, et al. The Study of Cardiovascular Risk in Adolescents--ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents [published correction appears in BMC Public Health. 2015;15:850]. BMC Public Health. 2015;15:94.) To assess the nutritional status of the participants, the WHO reference curves were adopted, the BMI-for-age being used according to sex. Those with a score of +1 > Z ≥ −2 were considered to be of normal weight, whereas those with an index of +2 > Z ≥ +1 or Z ≥ +2 were considered to be overweight or obese, respectively.1919 Bloch KV, Klein CH, Szklo M, Kuschnir MC, Abreu Gde A, Barufaldi LA, et al. ERICA: prevalences of hypertension and obesity in Brazilian adolescents. Rev Saude Publica. 2016;50 Suppl 1(Suppl 1):9s.

20 de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007;85(9):660-667. https://doi.org/10.2471/BLT.07.043497
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-2121 de Onis M. World Health Organization References Curves [monograph on the Internet]. 2006 [cited 2021 Apr 2]. Available from: http://ebook.ecog-obesity.eu
http://ebook.ecog-obesity.eu...

Calcifediol or 25-hydroxyvitamin D3-25(OH)D-is produced in the liver by the hydroxylation of vitamin D3 (cholecalciferol) by the vitamin D enzyme 25-hydroxylase and is the most stable form of vitamin D, maintaining high levels of vitamin D that reflect both sunlight exposure and dietary intake. Because 25(OH)D has a long half-life of approximately 24 h, it is routinely used to assess vitamin D status,2222 Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;95(6):1357-1364. https://doi.org/10.3945/ajcn.111.031070
https://doi.org/10.3945/ajcn.111.031070...
and its levels were measured by chemiluminescence microparticle immunoassay using a LIAISON 5000 series analyzer (DiaSorin Inc., Stillwater, MN, USA) and the DiaSorin kit. The coefficient of variation in percentage of this test varies from 3% to 8%, and its precision is 0.92 (95% CI, 0.90-0.94).1414 de Oliveira CL, Cureau FV, Cople-Rodrigues CDS, Giannini DT, Bloch KV, Kuschnir MCC, et al. Prevalence and factors associated with hypovitaminosis D in adolescents from a sunny country: Findings from the ERICA survey. J Steroid Biochem Mol Biol. 2020;199:105609. https://doi.org/10.1016/j.jsbmb.2020.105609
https://doi.org/10.1016/j.jsbmb.2020.105...
) For analysis purposes, serum 25(OH)D levels were stratified into insufficient/deficient (< 20 ng/mL) or sufficient (≥ 20 ng/mL), based on the criteria adopted by the Department of Bone and Mineral Metabolism of the Brazilian Society of Endocrinology and Metabolism in 2017.2323 Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) [homepage on the Internet]. São Paulo: SBEM; c2017 [cited 2021 Jan 5]. Vitamin D: New Reference Values. Available from: https://endocrino.org.br/vitamina-d-novos-valores-de-referencia/
https://endocrino.org.br/vitamina-d-novo...

Vitamin D dietary intake was assessed using a food record of all the meals consumed in the previous 24 h, including portion sizes and preparation methods. The data were collected using a software designed specifically for the ERICA.1414 de Oliveira CL, Cureau FV, Cople-Rodrigues CDS, Giannini DT, Bloch KV, Kuschnir MCC, et al. Prevalence and factors associated with hypovitaminosis D in adolescents from a sunny country: Findings from the ERICA survey. J Steroid Biochem Mol Biol. 2020;199:105609. https://doi.org/10.1016/j.jsbmb.2020.105609
https://doi.org/10.1016/j.jsbmb.2020.105...
,1818 Souza Ade M, Barufaldi LA, Abreu Gde A, Giannini DT, de Oliveira CL, dos Santos MM, et al. ERICA: intake of macro and micronutrients of Brazilian adolescents. Rev Saude Publica. 2016;50 Suppl 1(Suppl 1):5s. https://doi.org/10.1590/s01518-8787.2016050006698
https://doi.org/10.1590/s01518-8787.2016...
,2424 Barufaldi LA, Abreu Gde A, Veiga GV, Sichieri R, Kuschnir MC, Cunha DB, et al. Software to record 24-hour food recall: application in the Study of Cardiovascular Risks in Adolescents. Rev Bras Epidemiol. 2016;19(2):464-468. https://doi.org/10.1590/1980-5497201600020020
https://doi.org/10.1590/1980-54972016000...
After converting each food item to weight (g), the corresponding nutritional composition of each food was obtained by standardized tables, and the total diet of each participant was calculated. An intake of at least 400 IU/day of vitamin D was considered adequate.2525 Zhang R, Naughton DP. Vitamin D in health and disease: current perspectives. Nutr J. 2010;9:65. https://doi.org/10.1186/1475-2891-9-65
https://doi.org/10.1186/1475-2891-9-65...

Statistical analyses were performed with the Stata statistical software package, version 14 (StataCorp LP, College Station, TX, USA), using the set of commands for analyzing survey data with a complex sample (survey). Considering the sample size and the high prevalence of asthma (> 10%), the associations between serum 25(OH)D levels, prevalence of AA, and other study variables were assessed by bivariate Poisson regression models, using prevalence ratio (PR) and respective 95% CI.2626 Zhang J, Yu KF. What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA. 1998;280(19):1690-1691. https://doi.org/10.1001/jama.280.19.1690
https://doi.org/10.1001/jama.280.19.1690...
) Then, generalized linear models with Poisson family distribution were set up to analyze associations between 25(OH)D levels adjusted for potential confounding factors in the bivariate analysis (p < 0.20). For comparison between the means of continuous variables, ANOVA and the Student’s t-test were used. The present study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Research Ethics Committee of the Institute of Studies in Public Health of the Federal University of Rio de Janeiro (Protocol no. 45/2008).

RESULTS

Between February of 2013 and November of 2014, 1,152 adolescents underwent serum 25(OH)D determinations in the selected cities. Those who did not answer the question about asthma were excluded, the final sample consisting of 1,053 participants (91.4%). The prevalence of asthma in the sample was 15.4%, and insufficient levels of vitamin D were detected in 21.4%. The sociodemographic characteristics of the sample are described in Table 1.

Table 1
Sociodemographic characteristics of the sample.

Table 2 shows the distribution of the prevalence of AA according to sociodemographic characteristics, serum 25(OH)D levels, and nutritional status. There was a significantly higher prevalence of AA among those between 15 and 17 years of age and studying at private schools. Rio de Janeiro had the lowest prevalence of asthma. There was no association between insufficient levels of 25(OH)D and asthma.

Table 2
Prevalence of active asthma in relation to sociodemographic characteristics, nutritional status, and serum 25-hydroxyvitamin D3 levels.

Table 3 shows the distribution of the variables related to vitamin D according to the cities studied. The city of Rio de Janeiro, when compared with the other cities, had the lowest prevalence of vitamin D insufficiency (< 20 ng/mL), the lowest level of inadequate vitamin D intake (< 400 IU/day), and the highest serum 25(OH)D levels, and such differences were statistically significant. Although vitamin D intake (µg/day) was also higher in Rio de Janeiro, this difference was not statistically significant when compared with the other cities. However, no significant associations were found between the prevalence of AA and vitamin D-related variables in any of the cities (data not shown).

Table 3
Distribution of vitamin D-related variables according to the cities evaluated.

When the total sample was analyzed, those with an intake < 400 IU/day had lower serum 25(OH)D levels than did those with an intake of ≥ 400 IU/day (ANOVA; p < 0.001) or those with vitamin D insufficiency (17.2% vs. 11.0%; PR = 1.18; 95% CI: 0.34-4.62). However, the latter association was not statistically significant.

The comparison between the participants in Porto Alegre and those in Rio de Janeiro regarding the prevalence of asthma and vitamin D-related variables remained significant regardless of adjustments for sex, age group, nutritional status, physical activity, and screen time (Table 4). In addition, the mean serum levels of 25(OH)D were significantly lower in Porto Alegre (p < 0.0001). However, vitamin D intake (µg/day) did not differ between the two cities (p = 0.12).

Table 4
Comparison between Rio de Janeiro and Porto Alegre regarding the prevalence of active asthma and vitamin D-related variables.

DISCUSSION

Despite the differences in the prevalence rates of asthma among the cities studied, no associations were found between insufficient low levels of vitamin D and asthma in our sample.

A study carried out in the USA with adult patients demonstrated a positive correlation between serum vitamin D levels and lung function parameters (higher FEV1 and FVC).2727 Black PN, Scragg R. Relationship between serum 25-hydroxyvitamin d and pulmonary function in the third national health and nutrition examination survey. Chest. 2005;128(6):3792-3798. https://doi.org/10.1378/chest.128.6.3792
https://doi.org/10.1378/chest.128.6.3792...
) In the city of Viçosa, Brazil,2828 Peçanha MB, Freitas RB, Moreira TR, Silva LS, Oliveira LL, Cardoso SA. Prevalence of vitamin D deficiency and its relationship with factors associated with recurrent wheezing. J Bras Pneumol. 2019;45(1):e20170431. https://doi.org/10.1590/1806-3713/e20170431
https://doi.org/10.1590/1806-3713/e20170...
124 patients in the 0-to 18-year age bracket were studied in order to correlate recurrent wheezing with serum vitamin D concentrations. There was an association between vitamin D deficiency and wheezing, and the authors raised the hypothesis that there is a greater susceptibility to acute respiratory tract infections with the onset of wheezing in the first year of life due to reduced serum levels of this vitamin and concluded that vitamin D supplementation was a protective factor for the studied population.2828 Peçanha MB, Freitas RB, Moreira TR, Silva LS, Oliveira LL, Cardoso SA. Prevalence of vitamin D deficiency and its relationship with factors associated with recurrent wheezing. J Bras Pneumol. 2019;45(1):e20170431. https://doi.org/10.1590/1806-3713/e20170431
https://doi.org/10.1590/1806-3713/e20170...

Several studies have found evidence that vitamin D plays an important role in the pathogenesis of asthma by reducing airway inflammation through modulation of the immune system or improving the anti-inflammatory function of corticosteroids.2929 Wu AC, Tantisira K, Li L, Fuhlbrigge AL, Weiss ST, Litonjua A; et al. Effect of vitamin D and inhaled corticosteroid treatment on lung function in children. Am J Respir Crit Care Med. 2012;186(6):508-513. https://doi.org/10.1164/rccm.201202-0351OC
https://doi.org/10.1164/rccm.201202-0351...

30 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(5):1294-1296. https://doi.org/10.1016/j.jaci.2010.12.016
https://doi.org/10.1016/j.jaci.2010.12.0...
-3131 Yadav M, Mittal K. Effect of vitamin D supplementation on moderate to severe bronchial asthma. Indian J Pediatr. 2014;81(7):650-654. https://doi.org/10.1007/s12098-013-1268-4
https://doi.org/10.1007/s12098-013-1268-...

Among the immunomodulatory properties of vitamin D, its action on innate immunity stands out: it reduces pro-inflammatory cytokines and increases autophagosomal and autophagic activity, as well as the adaptive immune response, characterized by the inhibition of T-cell proliferation (Th1, Th2, and Th17). Moreover, it reduces the expression of IL-2 and INF-γ, stimulates the suppression of cytotoxic T response, and increases the number of regulatory T cells, IL-10, and IgG4.66 Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008;8(9):685-698. https://doi.org/10.1038/nri2378
https://doi.org/10.1038/nri2378...
,3232 Pfeffer PE, Mann EH, Hornsby E, Chambers ES, Chen YH, Rice L, et al. Vitamin D influences asthmatic pathology through its action on diverse immunological pathways. Ann Am Thorac Soc. 2014;11 Suppl 5:S314-S321. https://doi.org/10.1513/AnnalsATS.201405-204AW
https://doi.org/10.1513/AnnalsATS.201405...
,3333 Amorim CLCG, Oliveira JM, Rodrigues A, Furlanetto KC, Pitta F. Vitamin D: association with eosinophil counts and IgE levels in children with asthma. J Bras Pneumol. 2020;47(1):e20200279. https://doi.org/10.36416/1806-3756/e20200279
https://doi.org/10.36416/1806-3756/e2020...
Clinically, a reduction in the incidence of infections, a better response to corticosteroids in asthma patients, and improvements in pulmonary function are observed, thus avoiding airway remodeling.3232 Pfeffer PE, Mann EH, Hornsby E, Chambers ES, Chen YH, Rice L, et al. Vitamin D influences asthmatic pathology through its action on diverse immunological pathways. Ann Am Thorac Soc. 2014;11 Suppl 5:S314-S321. https://doi.org/10.1513/AnnalsATS.201405-204AW
https://doi.org/10.1513/AnnalsATS.201405...
However, according to some authors,3434 Reyes-Angel J, Han YY, Litonjua AA, Celedón JC. Diet and asthma: Is the sum more important than the parts?. J Allergy Clin Immunol. 2021;148(3):706-707. https://doi.org/10.1016/j.jaci.2021.04.030
https://doi.org/10.1016/j.jaci.2021.04.0...
the results of experimental studies that link specific dietary components to immunological changes and airway responses or inflammation rarely translate into consistent randomized controlled trials, and, so far, none has been recommended as a preventive or therapeutic agent for asthma.

A study carried out in 2017 and involving 289 children and adolescents (9-19 years) in the city of Lima, Peru, 137 of whom had asthma, raised the hypothesis that the free circulating form of vitamin D is biologically active and more associated with asthma and atopy than are total serum levels of vitamin D. The authors suggested that total serum levels of vitamin D might explain the contradictions in the results found in the literature.3535 Pollard SL, Lima JJ, Mougey E, Romero K, Tarazona-Meza C, Tomaino K, et al. Free 25(OH)D concentrations are associated with atopy and lung function in children with asthma. Ann Allergy Asthma Immunol. 2017;119(1):37-41. https://doi.org/10.1016/j.anai.2017.04.021
https://doi.org/10.1016/j.anai.2017.04.0...

In our study, we adopted the new cutoff points for total serum levels of vitamin D recommended by the Brazilian Society of Endocrinology and Metabolism.2323 Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) [homepage on the Internet]. São Paulo: SBEM; c2017 [cited 2021 Jan 5]. Vitamin D: New Reference Values. Available from: https://endocrino.org.br/vitamina-d-novos-valores-de-referencia/
https://endocrino.org.br/vitamina-d-novo...
) These current values started to be used after considerations of which serum levels truly reflected the greatest harm to health and, consequently, the real need for vitamin D supplementation. The current consensus is that vitamin D levels < 10 ng/mL present health risks and require supplementation. The previous criteria used in order to classify vitamin D insufficiency, deficiency, and sufficiency (< 20 ng/mL; ≥ 20 ≤ 29 ng/mL, and > 30 ng/mL, respectively) have been discussed by various medical societies due to the worldwide hypovitaminosis D “epidemic”, regardless of the different sociodemographic and cultural characteristics of the studied populations.2323 Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) [homepage on the Internet]. São Paulo: SBEM; c2017 [cited 2021 Jan 5]. Vitamin D: New Reference Values. Available from: https://endocrino.org.br/vitamina-d-novos-valores-de-referencia/
https://endocrino.org.br/vitamina-d-novo...
However, there was no association between serum 25(OH)D levels and asthma in our sample, even when the old cutoff points were used (data not shown).

Exposure to sunlight is an important factor for the absorption of vitamin D. Brazil is a tropical country, of continental dimensions, and great heterogeneity of climate. Most of the country is located between the Equator and the Tropic of Capricorn, which makes it one of the largest countries in the world in terms of land with high exposure to solar radiation throughout the year.3636 Schalka S, Steiner D, Ravelli FN, Steiner T, Terena AC, Marçon CR, et al. Brazilian consensus on photoprotection. An Bras Dermatol. 2014;89(6 Suppl 1):1-74. https://doi.org/10.1590/abd1806-4841.20143971
https://doi.org/10.1590/abd1806-4841.201...
) Serum concentrations of 25(OH)D vary according to geographic region and latitude and are higher in countries located close to the Equator.3737 Premaor MO, Furlanetto TW. Vitamin D deficiency in adults: to better understand a new presentation of an old disease [Article in Portuguese]. Arq Bras Endocrinol Metabol. 2006;50(1):25-37. https://doi.org/10.1590/S0004-27302006000100005
https://doi.org/10.1590/S0004-2730200600...

Of the four cities studied, Fortaleza (latitude: 03°43’02” S) and Rio de Janeiro (latitude: 22°54′23″ S) had the lowest prevalences of vitamin D insufficiency and higher serum 25(OH)D levels. In contrast, the prevalences of hypovitaminosis D were higher in Porto Alegre (latitude: 30°01′59″ S) and in Brasilia (latitude: 15°46′46″ S) than in the other two cities, and it could be explained by the large differences in latitude among them.1414 de Oliveira CL, Cureau FV, Cople-Rodrigues CDS, Giannini DT, Bloch KV, Kuschnir MCC, et al. Prevalence and factors associated with hypovitaminosis D in adolescents from a sunny country: Findings from the ERICA survey. J Steroid Biochem Mol Biol. 2020;199:105609. https://doi.org/10.1016/j.jsbmb.2020.105609
https://doi.org/10.1016/j.jsbmb.2020.105...

The seasons also affect serum concentrations of 25(OH)D. When blood collection is performed in winter, the chance of hypovitaminosis D is greater.1414 de Oliveira CL, Cureau FV, Cople-Rodrigues CDS, Giannini DT, Bloch KV, Kuschnir MCC, et al. Prevalence and factors associated with hypovitaminosis D in adolescents from a sunny country: Findings from the ERICA survey. J Steroid Biochem Mol Biol. 2020;199:105609. https://doi.org/10.1016/j.jsbmb.2020.105609
https://doi.org/10.1016/j.jsbmb.2020.105...
) In the present study, fewer blood samples were collected during summer due to school holidays. There is little seasonal variation in temperature in Rio de Janeiro and Fortaleza, whereas the climate is dry and there is little variation in solar radiation throughout the year in Brasília.3838 Tiba C, Fraidenraich N, Moskowicz M, Cavalcanti ESC, Lyra FJM, Nogueira AMB, Grossi Gallegos H. Atlas Solarimétrico do Brasil. Editora Universitária da UFPE; 2000. 111 p) In Porto Alegre, however, climatic seasons are more clearly defined. In any case, there was no statistically significant association between the season at blood sampling and the prevalence of AA in our sample.

Interestingly, we found that the city of Rio de Janeiro, when compared with the other cities, showed significant favorable differences regarding vitamin D-related variables and the prevalence of AA. However, these findings were independent of the association between asthma and vitamin D levels.

Exploratory analysis comparing the distribution of these variables showed that the prevalences of asthma and vitamin D insufficiency was significantly higher in Porto Alegre (in southern Brazil) than in Rio de Janeiro (on the southeastern coast of Brazil) regardless of possible confounding factors. In addition to geographic distance, these two cities have important differences in climate, dietary habits, and rate of exposure to solar radiation.

In our sample, the lowest serum level of 25(OH)D was found among adolescents with a vitamin D intake of < 400 IU/day, suggesting a positive relationship between vitamin D intake and serum levels. Foods such as salmon, tuna, and cod liver oil, which are rich in vitamin D, are not usually consumed by Brazilian adolescents, who, in general, have shown a decline in healthy eating habits and consuming more processed foods.1414 de Oliveira CL, Cureau FV, Cople-Rodrigues CDS, Giannini DT, Bloch KV, Kuschnir MCC, et al. Prevalence and factors associated with hypovitaminosis D in adolescents from a sunny country: Findings from the ERICA survey. J Steroid Biochem Mol Biol. 2020;199:105609. https://doi.org/10.1016/j.jsbmb.2020.105609
https://doi.org/10.1016/j.jsbmb.2020.105...
,3939 Alves MA, Souza AM, Barufaldi LA, Tavares BM, Bloch KV, Vasconcelos FAG. Dietary patterns of Brazilian adolescents according to geographic region: an analysis of the Study of Cardiovascular Risk in Adolescents (ERICA). Cad Saude Publica. 2019;35(6):e00153818. https://doi.org/10.1590/0102-311x00153818
https://doi.org/10.1590/0102-311x0015381...
) Among the cities participating in the study, Porto Alegre had the lowest mean intake of vitamin D in µg, the highest rate of vitamin D insufficiency, and a high prevalence of asthma. Although proper nutrition is essential, it does not seem to be the only requirement for achieving acceptable levels of this vitamin.3737 Premaor MO, Furlanetto TW. Vitamin D deficiency in adults: to better understand a new presentation of an old disease [Article in Portuguese]. Arq Bras Endocrinol Metabol. 2006;50(1):25-37. https://doi.org/10.1590/S0004-27302006000100005
https://doi.org/10.1590/S0004-2730200600...
,4040 Andrade PCO, Castro LS, Lambertucci MS, Lacerda MIPB, Araújo VPRJ, Bremm TAL, et al. Diet, sun exposure, and dietary supplementation: effect on serum levels of vitamin D. Rev Med Minas Gerais. 2015;25(3):432-437. https://doi.org/10.5935/2238-3182.20150082
https://doi.org/10.5935/2238-3182.201500...

Cultural habits, the use of sunscreen, skin color, and the seasons of the year are among the factors that affect the absorption of vitamin D.4040 Andrade PCO, Castro LS, Lambertucci MS, Lacerda MIPB, Araújo VPRJ, Bremm TAL, et al. Diet, sun exposure, and dietary supplementation: effect on serum levels of vitamin D. Rev Med Minas Gerais. 2015;25(3):432-437. https://doi.org/10.5935/2238-3182.20150082
https://doi.org/10.5935/2238-3182.201500...
) Rio de Janeiro showed higher vitamin D sufficiency, higher vitamin D intake (≥ 400 IU/day), and significantly higher serum levels of 25(OH)D when compared with the other cities studied, as well as showing a lower prevalence of AA. However, no significant associations were found between the prevalence of AA and vitamin D-related variables in any of the cities.

Some limitations of the study design should be considered, such as the impossibility of inferring causality for the associations found. The absence of lung function measurements due to the sample size and logistical issues made it difficult to compare our results with those of other studies that evaluated the association between asthma and vitamin D deficiency. On the other hand, the use of standardized procedures and trained staff ensured the good quality of the data. Furthermore, the random selection of participants and the sample size had sufficient power to ensure the reliability of the results obtained. Finally, the inclusion of geographic areas at different latitudes allowed the analysis of a large number of important confounding variables related to the association studied (exposure to sunlight, different lifestyles, and diet).

In conclusion, no association was found between AA and low levels of vitamin D in adolescents living at different latitudes in Brazil. Further studies are needed to elucidate whether this nutrient has any effect on asthma in a country with one of the highest incidences of solar radiation in the world.

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    Andrade PCO, Castro LS, Lambertucci MS, Lacerda MIPB, Araújo VPRJ, Bremm TAL, et al. Diet, sun exposure, and dietary supplementation: effect on serum levels of vitamin D. Rev Med Minas Gerais. 2015;25(3):432-437. https://doi.org/10.5935/2238-3182.20150082
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  • Financial support:

    None.
  • 2
    Study carried out at the Universidade do Estado do Rio de Janeiro - UERJ - Rio de Janeiro (RJ) Brasil.

Publication Dates

  • Publication in this collection
    15 Dec 2021
  • Date of issue
    2021

History

  • Received
    28 July 2021
  • Accepted
    08 Sept 2021
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