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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

From Medscape Medical News 

Vitamin D Insufficiency Linked to Asthma Severity CME/CE News Author: Laurie Barclay, MDCME Author: Charles Vega, MD, FAAFP 

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

May 4, 2009 — Vitamin D insufficiency is linked to asthma severity, according to the results of a cross-sectional study reported in the May 1 issue of the American Journal of Respiratory and Critical CareMedicine.

"Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in earlychildhood," 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 andmarkers 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 in616 Costa Rican children aged 6 to 14 years. Univariate and multivariate analyses were performed with useof linear, logistic, and negative binomial regressions. Increased airway responsiveness was defined as a8.58-µmol or less provocative dose of methacholine producing a 20% decrease in baseline forcedexpiratory volume in 1 second.

Levels of vitamin D were insufficient (< 30 ng/mL) in 175 (28%) of 616 children with asthma. Vitamin Dlevels 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 withlower 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 childrenwith asthma," the study authors write. "In these children, lower vitamin D levels are associated withincreased markers of allergy and asthma severity."

Limitations of this study include debate regarding what constitutes a normal circulating vitamin D level, lackof 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 thatvitamin D might play, if any, in established human allergy and asthma," the study authors conclude. "Thesestudies should include in vitro and animal studies to further elucidate the mechanisms for the role of vitaminD, 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, UnitedKingdom, and colleagues discuss the difficult scientific, ethical, and regulatory issues involved inintervention 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 ethicalor regulatory concerns, would fail to address the scientific evidence that larger vitamin D intakes (e.g., 2,000IU/d) may be required for beneficial nonskeletal effects," the editorialists write. "While these concerns maybe satisfactorily addressed, it remains to be seen whether pregnant women, parents, or patients will besimilarly 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 optimalintake 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 toDiaSorin Corporation. Another study author has disclosed various financial and/or other relationships with

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 AstraZeneca, Boehringer Ingelheim, Genentech, Glaxo-Wellcome, Roche Pharmaceuticals, Pfizer,Schering Plough, Variagenics, Genome Therapeutics, and Merck Frost. The editorialists have disclosed norelevant 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, whichaccompanies 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 hasdemonstrated 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 arelimited 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. Allchildren completed questionnaires regarding asthma severity, as well as pulmonary functiontesting, methacholine challenge testing, allergy skin testing, and measurement of total andallergen-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 levelsbetween 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 findingsamong this cohort, and 91% of children had experienced an unscheduled medical visit for asthmain the past year. Despite this, only 39% had received an anti-inflammatory medication in the lastyear.

• 3.4% of participants had vitamin D deficiency, and another 24.6% were considered to have aninsufficient amount of vitamin D.

• 25(OH)D levels were inversely related to total IgE and eosinophil levels. For each 10-ng/mLincrease in 25(OH)D levels in an average male subject, serum total IgE levels and eosinophilcounts 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 challengetests, but there was no independent effect of 25(OH)D levels on the mean forced expiratory volumein 1 second.

• Finally, vitamin D levels were inversely associated with the risk for hospitalization for asthma in theprevious year.

• In full confirmatory analysis, vitamin D levels were unrelated to the use of anti-inflammatorymedications.

Clinical Implications

• Approximately 90% of vitamin D in humans is derived from the sun, but many individuals in sunnyareas still have vitamin D deficiency. Vitamin D is found in oily fish and egg yolks, and it has beendemonstrated to have immunomodulating effects.

• The current study of asthmatic children demonstrates that serum vitamin D levels are inverselyrelated to serum total IgE levels and eosinophilia counts, airway hyperresponsiveness, and hospitaladmissions for asthma. However, vitamin D levels were unrelated to the mean forced expiratoryvolume in 1 second.

CME/CE Test

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

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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 eggsAll of the following outcomes were inversely related to serum vitamin D levels in the current studyby Forno and colleagues of children with asthma except :

Airway hyperresponsiveness

Forced expiratory volume in 1 second

Serum eosinophil count

Hospitalizations for asthma

Save and Proceed

This article is a CME/CE certified activity. To earn credit for this activity visit:http://cme.medscape.com/viewarticle/702161

Authors and DisclosuresAs an organization accredited by the ACCME, MedscapeCME requires everyone who is in a position tocontrol the content of an education activity to disclose all relevant financial relationships with anycommercial interest. The ACCME defines "relevant financial relationships" as financial relationships in anyamount, 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 productsregulated 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 WashingtonUniversity, Washington, DC; Nurse Practitioner, School-Based Health Centers, Baltimore City PublicSchools, Baltimore, Maryland

Disclosure: Laurie Scudder, MS, NP, has disclosed no relevant financial information.

CME Author(s)

Charles P. Vega, MD

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Charles P. Vega, MD, FAAFP, is an associate professor and residency director in theDepartment of Family Medicine at the University of California, Irvine.

Disclosure: Charles Vega, MD, FAAFP, has disclosed no relevant financial relationships.

Medscape Medical News © 2009 MedscapeCMEThe material presented here does not necessarily reflect the views of Medscape or companies that support educationalprogramming on www.medscapecme.com. These materials may discuss therapeutic products that have not been approved bythe US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should beconsulted before using any therapeutic product discussed. Readers should verify all information and data before treatingpatients 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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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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