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From Medscape Medical News

Vitamin D Insufficiency Linked to Asthma Severity

News Author: Laurie Barclay, MD CME Author: Charles Vega, MD, FAAFP CME/CE Released: 05/04/2009; Valid for credit through 05/04/2010

CME/CE

May 4, 2009 Vitamin D insufficiency is linked to asthma severity, according to the results of a crosssectional study reported in the May 1 issue of the American Journal of Respiratory and Critical Care Medicine. "Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood," write Erick Forno, from Brigham and Women's Hospital in Boston, Massachusetts, and colleagues. "However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood." The goal of this study was to evaluate the association between measured levels of 25-hydroxyvitamin D ([25(OH)D]; the predominant circulating form of vitamin D) and markers of asthma severity and allergy in 616 Costa Rican children aged 6 to 14 years. Univariate and multivariate analyses were performed with use of linear, logistic, and negative binomial regressions. Increased airway responsiveness was defined as a 8.58-mol or less provocative dose of methacholine producing a 20% decrease in baseline forced expiratory volume in 1 second. Levels of vitamin D were insufficient (< 30 ng/mL) in 175 (28%) of 616 children with asthma. Vitamin D levels were significantly and inversely associated with total immunoglobulin E (IgE) and eosinophil count, based on multivariate linear regression models. A log10-unit increase in vitamin D levels was associated with lower odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004 - 0.71; P = .03), any use of anti-inflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05 - 0.67; P = .01), and increased airway responsiveness (OR, 0.15; 95% CI, 0.024 - 0.97; P = .05), according to multivariate logistic regression models. "Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma," the study authors write. "In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity." Limitations of this study include debate regarding what constitutes a normal circulating vitamin D level, lack of a control group, cross-sectional design, and possible residual confounding by socioeconomic status. "Our data suggest that additional work needs to be done to determine the potential beneficial role that vitamin D might play, if any, in established human allergy and asthma," the study authors conclude. "These studies should include in vitro and animal studies to further elucidate the mechanisms for the role of vitamin D, and eventual clinical trials of vitamin D supplementation to prevent exacerbations. In addition, common polymorphisms in the vitamin D receptor and other genes in the vitamin D pathway should be further characterized, especially as they relate to circulating vitamin D levels and asthma severity." In an accompanying editorial, Graham Devereux, MD, from the University of Aberdeen in Aberdeen, United Kingdom, and colleagues discuss the difficult scientific, ethical, and regulatory issues involved in intervention studies of vitamin D in the primary prevention and treatment of asthma. "Studies that supplement with the currently recommended doses of vitamin D, while unlikely to raise ethical or regulatory concerns, would fail to address the scientific evidence that larger vitamin D intakes (e.g., 2,000 IU/d) may be required for beneficial nonskeletal effects," the editorialists write. "While these concerns may be satisfactorily addressed, it remains to be seen whether pregnant women, parents, or patients will be similarly convinced and participate in such studies. Ultimately, it is only by investigating the effects of vitamin D in doses at, and above those currently recommended, that decisions can be made on the optimal intake of vitamin D for health and the possible prevention and treatment of asthma." The National Institutes of Health supported this study. One of the study authors has been a consultant to DiaSorin Corporation. Another study author has disclosed various financial and/or other relationships with

AstraZeneca, Boehringer Ingelheim, Genentech, Glaxo-Wellcome, Roche Pharmaceuticals, Pfizer, Schering Plough, Variagenics, Genome Therapeutics, and Merck Frost. The editorialists have disclosed no relevant financial relationships. Am J Respir Crit Care Med. 2009;179:739-742, 765-771.

Clinical Context
Vitamin D has significant effects on immune function, and an editorial by Devereux and colleagues, which accompanies the current article, reviews the metabolism of vitamin D. Humans obtain approximately 90% of their vitamin D through sunlight, with the remainder coming from diet. Despite this fact, research has demonstrated that more than half of individuals in places with high exposure to sunshine, such as Hawaii, still have evidence of vitamin D deficiency. Foods with significant levels of naturally occurring vitamin D are limited to oily fish and egg yolk, although dairy products are often fortified with vitamin D. Observational studies regarding the effects of vitamin D on asthma and allergy have yielded mixed results. The current study examines the effects of vitamin D on disease markers in asthmatic children.

Study Highlights
Study participants were Costa Rican children between the ages of 6 and 14 years with asthma. All children completed questionnaires regarding asthma severity, as well as pulmonary function testing, methacholine challenge testing, allergy skin testing, and measurement of total and allergen-specific serum IgE as well as peripheral blood eosinophils. The main outcome of the study was the relationship between these outcomes and serum levels of 25(OH)D. Vitamin D deficiency was defined as levels of 25(OH)D less than 20 ng/mL, and levels between 20 and 30 ng/mL indicated insufficient vitamin D. Researchers adjusted the study results to account for potential confounders, including age, sex, parental educational levels, and body mass index. 616 children provided study data. The mean age was 8.7 years, and 40% of participants were girls. Elevated total IgE levels, increased eosinophil count, and skin test reactivity were common findings among this cohort, and 91% of children had experienced an unscheduled medical visit for asthma in the past year. Despite this, only 39% had received an anti-inflammatory medication in the last year. 3.4% of participants had vitamin D deficiency, and another 24.6% were considered to have an insufficient amount of vitamin D. 25(OH)D levels were inversely related to total IgE and eosinophil levels. For each 10-ng/mL increase in 25(OH)D levels in an average male subject, serum total IgE levels and eosinophil counts fell by 25 IU/mL and 29 cells/m3, respectively. Vitamin D levels also were inversely related to the size of skin test reactivity to dust mites. Higher vitamin D levels predicted less airway hyperresponsiveness on methacholine challenge tests, but there was no independent effect of 25(OH)D levels on the mean forced expiratory volume in 1 second. Finally, vitamin D levels were inversely associated with the risk for hospitalization for asthma in the previous year. In full confirmatory analysis, vitamin D levels were unrelated to the use of anti-inflammatory medications.

Clinical Implications
Approximately 90% of vitamin D in humans is derived from the sun, but many individuals in sunny areas still have vitamin D deficiency. Vitamin D is found in oily fish and egg yolks, and it has been demonstrated to have immunomodulating effects. The current study of asthmatic children demonstrates that serum vitamin D levels are inversely related to serum total IgE levels and eosinophilia counts, airway hyperresponsiveness, and hospital admissions for asthma. However, vitamin D levels were unrelated to the mean forced expiratory volume in 1 second.

CME/CE Test

Which of the following statements regarding the metabolism of vitamin D is most accurate?

Humans derive 25% of their vitamin D from sunlight Vitamin D deficiency is nearly nonexistent in equatorial areas with high sun exposure Vitamin D has not yet been demonstrated to affect the human immune system Vitamin D is found naturally in oily fish and eggs All of the following outcomes were inversely related to serum vitamin D levels in the current study by Forno and colleagues of children with asthma except: Airway hyperresponsiveness Forced expiratory volume in 1 second Serum eosinophil count Hospitalizations for asthma
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This article is a CME/CE certified activity. To earn credit for this activity visit: http://cme.medscape.com/viewarticle/702161

Authors and Disclosures

As an organization accredited by the ACCME, MedscapeCME requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest. MedscapeCME encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

Author(s)
Laurie Barclay, MD

Laurie Barclay, MD, is a freelance writer and reviewer for Medscape. Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Editor(s)
Brande Nicole Martin

Brande Nicole Martin is the News CME editor for Medscape Medical News. Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

Nurse Planner
Laurie Scudder, MS, NP

Laurie E. Scudder, MS, NP, Accreditation Coordinator, Continuing Professional Education Department, Medscape, LLC; Clinical Assistant Professor, School of Nursing and Allied Health, George Washington University, Washington, DC; Nurse Practitioner, School-Based Health Centers, Baltimore City Public Schools, Baltimore, Maryland Disclosure: Laurie Scudder, MS, NP, has disclosed no relevant financial information.

CME Author(s)
Charles P. Vega, MD

Charles P. Vega, MD, FAAFP, is an associate professor and residency director in the Department of Family Medicine at the University of California, Irvine. Disclosure: Charles Vega, MD, FAAFP, has disclosed no relevant financial relationships.

Medscape Medical News 2009 MedscapeCME The material presented here does not necessarily reflect the views of Medscape or companies that support educational programming on www.medscapecme.com. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity. Send press releases and comments to news@medscape.net.
This article is a CME/CE certified activity. To earn credit for this activity visit: http://cme.medscape.com/viewarticle/702161

CME/CE Information
CME/CE Released: 05/04/2009; Valid for credit through 05/04/2010

Target Audience
This article is intended for primary care clinicians, pulmonary medicine specialists, allergists, and other specialists who care for children at risk for asthma.

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The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Learning Objectives
Upon completion of this activity, participants will be able to:

Describe the metabolism of vitamin D. Identify the effect of serum levels of vitamin D on disease markers of asthma.

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