Category Archives: Allergy

Did we trade rickets with allergy?

I have written on that before but find it striking again when reading another historical perspective.

The first insight into the possible relationship between the industrialization of Northern Europe and rickets was made by Sniadecki in 1822 when he concluded that children who lived in the inner city of Warsaw had a high incidence of rickets because of their lack of sun exposure. This was based on his clinical observations that children living in rural areas outside of Warsaw did not suffer from rickets while children born and raised in Warsaw were plagued with the disease.

Now we are supplementing vitamin D to nearly all inner city children who have a high allergy prevalence but not so much in rural areas where we see less allergy – everywhere, not only in Warsaw.

Did we trade rickets with allergy?

A bad study is worse than no study

“Direct infant UV light exposure is associated with eczema and immune development”.
Kristina Rueter, Anderson P. Jones, Aris Siafarikas, Ee-Mun Lim, Natasha Bear, Paul S. Noakes, Susan L. Prescott and Debra J. Palmer.
Article in press 2018 American Academy of Allergy, Asthma & Immunology https://doi.org/10.1016/j.jaci.2018.08.037

These graphical in JACI abstracts look a bit strange like “science for dummies”. It lets me wonder if there isn’t a major discrepancy of title and abstract?

Objective: We sought to determine the effects of early postnatal vitamin D supplementation on infant eczema and immune development.
Methods: By using a double-blind randomized controlled trial, newborn infants were randomized to receive vitamin D supplementation (400 IU/d) or a placebo until 6 months of age. Some infants also wore personal UV dosimeters to measure direct UV light (290-380 nm) exposure. Infant vitamin D levels were measured at 3 and 6 months of age. Eczema, wheeze, and immune function outcomes were assessed at 6 months of age.
Results: At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater for the vitamin D–supplemented group than the placebo group, but there was no difference in eczema incidence between groups. Infants with eczema were found to have had less UV light exposure (median, 555 Joules per square meter [J/m2; interquartile range, 322-1210 J/m2]) compared with those without eczema (median, 998 J/m2 [interquartile range, 676-1577 J/m2]; P = .02). UV light exposure was also inversely correlated with IL-2, GM-CSF, and eotaxin production to Toll-like receptor ligands.
Conclusion: This study is the first to demonstrate an association between greater direct UV light exposures in early infancy with lower incidence of eczema and proinflammatory immune markers by 6 months of age. Our findings indicate that UV light exposure appears more beneficial than vitamin D supplementation as an allergy prevention strategy in early life.

IMHO this is a RCT of vitamin D supplementation of newborns and not a study of UV light exposure. Maybe the authors needed a selling point for a poorly designed study?

The (only) allergy outcome is shown in table. 6 of 90 in the placebo group and 9 of 90 in the vitamin group develop eczema. This translates into an OR of 1.6 (0.5-4.6, P = 0.4214). I read this as a non significant association of exposure and outcome which is quite understandable given

1. the low power of the study. My result of a post hoc power calculation is 12%.
2. the ignorance of the main eczema risk factor ( filaggrin mutation!). Allocation by a “history of maternal allergic disease” does not allocate filaggrin mutations equally between groups.
3. the ignorance of maternal vitamin D levels. Restricting to maternal levels >50 nmol/L introduced as a bias towards supplemented fetuses.
4. the ignorance of vitamin D fed by formula. So clearly this is only a done-finding study and not a RCT of vitamin D supplementation as also the controls are (heavily) exposed.
5. the ignorance of the most relevant outcome in this age group which is sensitization against food allergens.

Also the “vitamin D hypothesis” did not emerge to explain associations found between regions of higher latitudes and increased risk of development of allergic diseases in children. The references 2-5 are misleading. It emerged by theoretical considerations of the immune effects of artificial vitamin D supplementation.

Even the first RCT study in the field is not being cited. JACI is publishing again fake science.

Does Acinetobacter lwoffii F78 protect from allergy?

When reading a new Science immunology paper (“Inception of early-life allergen-induced airway hyperresponsiveness is reliant on IL-13+CD4+T cells“) one could again think that A. lwoffii could protect from the development of house mite allergy.

The paper, however, leaves it open (even doesn’t mention the result in the discussion) if this is any specific A. lwofii effect or just some some LPS  effect that antagonized the vitamin D containing food.

So no news even 10 years  after the initial Acinetobacter hype. The only verified fact remain several deaths caused by Acinetobacter in newborns.

Finding the allergy cause

Genomics did not really help to explain allergic mechanisms beyond IL33. But combining  now stem cell & immune cell Identity tracking looks like a promising strategy for identifying initial disease events. At least colleagues at the MDC  think so.

LifeTime – ein visionärer Vorschlag für ein EU-Flagschiff. Zuverlässig vorherzusagen, wann eine Krankheit ausbricht oder wie sie verläuft, erscheint wie ein Traum. Ein europäisches Konsortium will ihn Wirklichkeit werden lassen und dabei vor allem neue Technologien der Einzelzellbiologie nutzen. Führende Forscherinnen und Forscher haben daher einen Antrag für ein FET-Flagschiff mit dem Namen LifeTime eingereicht.

Unspezifische Impfeffekte als Allergieprävention?

Unspezifische Impfeffekte  wird es wohl  geben, so der neue SPON Artikel von heute

Allerdings wird in Industrienationen daran geforscht, wie die unspezifischen Effekte früher Impfungen möglicherweise ein Leben nachwirken. Zurzeit läuft zum Beispiel eine große Studie in Australien zur Frage, ob eine frühe BCG-Impfung (gegen Tuberkulose) das Allergierisiko senkt.
Vielleicht hängt der Anstieg von Allergien ja damit zusammen, dass wir aufgehört haben, gegen Pocken und BCG zu impfen”, vermutet Aaby. Er fragt sich sogar, ob das Einstellen der Pocken-Impfung nicht auch Schaden angerichtet haben könnte, weil nun das Immuntraining durch diese Impfung ausfalle.

Der Bezug zu den Allergien ist allerdings sehr unwahrscheinlich, siehe Arnoldusson

We identified 767 articles, of which 17 satisfied our inclusion criteria; there was only 1 randomized controlled trial, with the remaining studies being epidemiologic investigations. Meta-analyses did not show any protective effect of vaccination against the risk of sensitization, as judged by specific IgE tests or skin prick testing …BCG vaccination is unlikely to be associated with protection against the risk of allergic sensitization and disease.

Es ist mir also ziemlich schleierhaft, warum das Murdoch Childrens Research Institute dazu eine Studie macht. Aber das Research Institute hat schon ganz andere Flops produziert…

Auch die Pockenimpfung schützt nicht, das ist eigentlich längst abgehakt

We found no association between having been vaccinated against smallpox in childhood and risk of atopy or allergic rhinitis. Smallpox vaccination was associated with a slightly decreased risk of asthma. There was no association between age at smallpox vaccination and risk of atopy, allergic rhinitis, or asthma. Adjusting for birth cohort, sibship size, age of the woman’s mother at birth, and social class in childhood did not change these results.

Es geht hier auch nicht so sehr um eine neue wissenschaftliche Diskussion, sondern um die journalistische Aufarbeitung eines “Dokumentarfilms”.

Nach  Masernimpfung hat im übrigen Seif Shaheen in Guinea-Bissau mehr(!) Allergien gefunden, was aber wohl auch fraglich ist, da hier nicht nur die Impfung, sondern die medizinische Betreuung generell (“iatrogen”) zur Debatte steht. Interessanterweise wird in Guinea-Bissau auch Vitamin D zur Tbc Prophylaxe gegeben wobei Vitamin D selbst ein Allergierisikofaktor ist.

Gene methylation in newborns is changed by maternal vitamin D supplementation

A randomized controlled study of pregnant women examined 400 IU vitamin D3 vs 3,800 IU from the second trimester through 4-6 weeks postpartum by genome-wide DNA methylation in leukocytes.

At birth, intervention group mothers showed DNA methylation gain and loss at 76 and 89 cytosine- guanine (CpG) dinucleotides, respectively, compared to controls. Postpartum, methylation gain was noted at 200 and loss at 102 CpGs. Associated gene clusters showed strongest biologic relevance for cell migration/ motility and cellular membrane function at birth and cadherin signaling and immune function at postpartum.

It seems that D3 supplementation is generating epigenetic effects in the offspring, something that we predicted already in 2012 as programming of vitamin D sensitivity.

When re-annotating the genes above using biocLite(“mygene”) there are at least 2 interesting genes for gain of methylation are getting to the surface: ZMIZ1  T cell differentiation) and CYP7B1 (first reaction in the cholesterol catabolic pathway of extrahepatic tissues, which converts cholesterol to bile acids). But also methylation loss is interesting with HLA-A (antigen processing).

Framing

As a particular view, framing comprises a set of concepts and theoretical perspectives on how individuals, groups, and societies, organize, perceive, and communicate about reality. I believe it is not an inherent aspect of social sciences but of science in general. Take for an example allergy research: Framing in 1980 was air pollution, in 2000 it was hygiene and in 2018 it is omics while basic research is being largely ignored. So we could rewrite the framing article

Framing involves construction of a scientific reality– by pubmed, congresses, mass media, funding agencies, prize winners, or other scientists and organizations. Participation in a language community necessarily influences an individual scientists’s perception of the meanings attributed to words or phrases. Politically, the language communities of science, advertising, religion, and mass media are highly contested and evolve imperceptibly and organically over cultural time frames.

Esoteric science

“Planetary science” – just esoteric blahblah? Embracing the whole world? Exposome instead of enviromental exposure? The desperate reaction to many unresolved questions?

The importance of the exposome and allostatic load in the planetary health paradigm.
Logan AC, Prescott SL, Haahtela T, Katz DL.
In 1980, Jonas Salk encouraged professionals in anthropology and related disciplines to consider the interconnections between “planetary health,” sociocultural changes associated with technological advances, and the biology of human health. The concept of planetary health emphasizes that human health is intricately connected to the health of natural systems within the Earth’s biosphere; experts in physiological anthropology have illuminated some of the mechanisms by which experiences in natural environments (or the built environment) can promote or detract from health. For example, shinrin-yoku and related research (which first emerged from Japan in the 1990s) helped set in motion international studies that have since examined physiological responses to time spent in natural and/or urban environments. However, in order to advance such findings into planetary health discourse, it will be necessary to further understand how these biological responses (inflammation and the collective of allostatic load) are connected to psychological constructs such as nature relatedness, and pro-social/environmental attitudes and behaviors. The exposome refers to total environmental exposures-detrimental and beneficial-that can help predict biological responses of the organism to environment over time. Advances in “omics” techniques-metagenomics, proteomics, metabolomics-and systems biology are allowing researchers to gain unprecedented insight into the physiological ramifications of human behavior. Objective markers of stress physiology and microbiome research may help illuminate the personal, public, and planetary health consequences of “extinction of experience.” At the same time, planetary health as an emerging multidisciplinary concept will be strengthened by input from the perspectives of physiological anthropology.