Handout text 2011 AAAAI Seminar San Francisco Vitamin D deficiency

2011 AAAAI Annual Meeting Handout

Session Number: 3523
Session Title: Vitamin D: Vitamin D Deficiency Causes Asthma -> CON
Session Start: 3/20/2011 12:45 AM
Matthias Wjst, Munich

Welcome to the third major symposium on vitamin D and asthma at the AAAAI.

As a nuclear receptor, vitamin D is a highly interesting substance and involved in hundreds of biological processes. It is long known, that longtime sun deprivation is leading to bone disease. It may also not come unexpected that immune disease may develop if an important step in the steroid biosynthesis is being broken.

There is, however, no reason to believe that vitamin D deficiency causes asthma. Any association of vitamin D deficiency and asthma is very unlikely as during the most severe rickets epidemics in the 19th century, asthma was largely unknown (Wjst 2009). Upper respiratory infections, however, were common at that time with pneumonia being even the terminally leading illness.

Given the close relationship of asthma and respiratory infections it is therefore possible that changes in the vitamin D supply may indeed affect the course of asthma (which should not be confused with any causal role). Under severe deficiency situations, airway symptoms may be aggravated (Brehm 2009) with vitamin D supplements having steroid sparing effects (Xystrakis 2006). Interpretation of the recent cross-sectional studies, however, is difficult as vitamin D does not only have biological effects per se but is at the same time a “life-style” indicator. Ill people will spend less time outdoors and will have also lower levels of vitamin D.

With regard to allergy initiation, effects of early vitamin D supplementation are being controversially discussed. While we have consistently found that vitamin D drops are a major factor facilitating early sensitization, advocates of an opposite view will also find some support in the literature. The main problem is the sheer amount of papers published every year in vitamin D (N=3,000) as well as in allergy research (N=10,000). Even most recent expert reviews are missing relevant studies.

Single author reviews tend to be overly optimistic about effects of vitamin D supplementation while larger review panels are much more cautious ( see for example the 999 pages of the October 2010 Institute of Medicine Consensus Report on Dietary Reference Intakes for Calcium and Vitamin D http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx ).

To solve that controversial issue we probably need to agree on a few key points when examining the effects of vitamin D on asthma (and allergy):

(1) Results of animal studies can not be extrapolated to humans – we need to have human data

(2) It is important to differentiate supplement effects on humans by
 A. individual age: pregnancy/newborn/young/old child
B. preceding exposure by vitamin D (as it is being fat soluble)
C. individual genetic variation in vitamin D metabolism and signalling

(3) As with any other drug, vitamin D effects depend on
A. dose and pharmaceutical formulation
B. route of administration (skin, oral, intramuscular)
C. co-exposure with allergens

(4) Exact vitamin D metabolite measurements over time are necessary. Food frequency questionnaire are not sufficient; isolated 25-OH vitamin D serum levels have only limited explanatory value. We need repeated measurements where 1,25-OH2 has the main biological function.

(5) It is mandatory to differentiate outcomes: “all that wheezes is not asthma” while different developmental pathways of allergy and asthma need to be acknowledged. Disease initiating effects should be discriminated from disease aggravating factors.

(6) Interventional trials are required before giving any clinical recommendations.

Ignoring some of these points was probably the reason of the recent controversy around the epidemiological studies of vitamin D exposure in pregnancy. Results were largely discrepant: The Gale study reported a more than 5-fold increased risk on asthma by high maternal vitamin D serum levels, while the Devereux study showed a 0.3-fold reduced risk on wheezing by questionnaire derived exposure estimates. The discussion has been cleared only recently by a new study of Camargo who measured cord-blood levels of 25(OH)D and described an inverse associations with risk of respiratory infection and childhood wheezing but no association with incident asthma (Camargo 2011).

Vitamin D exposure of newborns continues to be a risk factor for allergic sensitization. There is evidence from several birth cohort studies that vitamin D exposure will lead to later allergy (summarized in Wjst 1999, Wjst 2006, Wjst 2009).

Randomized clinical trials are now urgently required, in pregnancy andthe newborn period while also treatment studies in asthma and COPD patients are promising. It is even possible that in the future, recommendations for vitamin D may be even opposite depending on age and genetic background.

Wjst M. Introduction of oral vitamin D supplementation and the rise of the allergy pandemic. Allergy Asthma Clin Immunol 2009 Nov 19;5(1):8.

Brehm JM, Schuemann B, Fuhlbrigge AL, Hollis BW, Strunk RC, Zeiger RS, Weiss ST, Litonjua AA; Childhood Asthma Management Program Research Group. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol 2010 Jul;126(1):52-8.e5. Epub 2010 Jun 9.

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. The Journal of Clinical Investigation 2006; 116: 146-55.

Camargo CA Jr, Ingham T, Wickens K, Thadhani R, Silvers KM, Epton MJ, Town GI, Pattemore PK, Espinola JA, Crane J. New Zealand Asthma and Allergy Cohort Study Group. Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics 2011;127(1):e180-7.

Wjst, M. The vitamin D slant on allergy. Pediatr Allergy Immunol 2006; 17: 477-83.

Wjst, M, Dold S. Genes, factor X, and allergens: what causes allergic diseases? Allergy 1999; 54: 757-9.