2013 APCAACI conference

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If I understand it correctly wheat is actually one of the more significant allergens with regard to the Asia-Pacific region and has more research emphasis. We deal with anaphylactic wheat (and barley, closely related grains) allergy in one child and I've never really run across any research on the US side for IgE-mediated.

It's hard to reign myself in from jumping to conclusions but my youngest child's profile matches MUCH more closely with children in AP region. Extreme sensitization to dust mite, wheat anaphylaxis and milk. I'm also starting to wonder if it's a bigger problem gaining critical mass as treatment adherence was cited as a challenge to resolution, or even seeking out treatment to begin with. Ashtma seems to be more acknowledged. The major theme was the changing environment as it relates to allergy, asthma and atopy.

COMPARISON OF SPECIFIC IGE ANTIBODIES TO WHEAT COMPONENT ALLERGENS IN TWO PHENOTYPES OF WHEAT ALLERGY
YOUNG-HEE NAM1, EUI-KYUNG HWANG2, HYUN JUNG JIN3, JEONG MIN LEE2, YOO-SEOB SHIN2, YOUNG-MIN YE2, ARANTXA PALACIN4, GABRIEL SALCEDO4, SOO-YOUNG LEE2, HAE-SIM PARK2
1Dong-A University, South Korea 2Ajou University, South Korea 3Yeungnam University, South Korea 4Unidad De Bioquimica, Spain

Background: Clinical manifestation of wheat allergy are various according to the sensitization routes. Specific IgE to gliadin was proposed a marker for wheat dependent exercise induced anaphylaxis (WDEIA), while Tri a 14 was found to induce IgE response in baker’s asthma.
To evaluate whether these components could be used for discriminating two major phenotypes of wheat allergy, anaphylaxis and/or urticaria and baker’s asthma.

Methods: Twenty-nine patients with wheat allergy and 30 non-atopic healthy controls were enrolled from Ajou University Hospital. Group I included wheat-induced anaphylaxis and/or urticaria (n = 21) and group II included baker’s asthma (n = 8). Total serum IgE levels and serum-specific IgE levels to wheat and gliadin were measured using the ImmunoCAP system, and serum-specific IgE to Tri a 14 by ELISA.
Results: The positive rate of skin prick test to wheat and serum-specific IgE to wheat was higher in group II than in group I, 41.7% vs. 75% and 71.4% vs. 87.5%, respectively. The prevalence of serum specific IgE to Tri a 14 was higher in group II (25%) than in group I (4.8%), while the serum specific IgE to gliadin was significantly higher in group I (70%) than in group II (12.5%). The cutoff value for predicting the baker’s asthma using the ratio of serum specific IgE to Tri a 14 to gliadin was 742.8 with 87.5% sensitivity and 83.3% specificity.

Conclusion(s): The sensitization rate to Tri a 14 was very low in patients of two major phenotypes of wheat allergy in an Asian population. These finding suggest that the ratio of serum specific IgE to Tri a 14 to gliadin may be a potential candidate marker for predicting the phenotype of baker’s asthma with high sensitivity and specificity.

ASSOCIATION OF MANNOSE-BINDING LECTIN WITH WORK-RELATED RESPIRATORY SYMPTOMS IN BAKERY WORKERS EXPOSED TO WHEAT FLOUR
MI-AE KIM, MOON KYUNG YOON, EUN-MI YANG, HYE-SOO YOO, SEUNG-HYUN KIM, YOO SEOB SHIN, YOUNG-MIN YE, DONG-HO NAHM
Ajou University, South Korea

Background: In order to investigate an innate immunity, we evaluated the role of mannose-binding lectin (MBL), one of the initiation components of complement cascade, in the mechanism of baker’s asthma.

Methods: A total of 385 bakery workers were included and subjects’ clinical data and questionnaires regarding work-related respiratory symptoms were collected. Serum specific IgE, IgG1, IgG4 to wheat flour and MBL were measured by ELISA and four MBL2 genes (-226G/A in the exon 1, -225G/C, -431A/C, and -554G/C in the promoter) were genotyped. Results: Mean age was 34.9±7.7 and male consisted 56.5%, smoker for 41.8%. Mean working period was 4.0±3.5 years and low exposure group consisted 28.2%, intermediate exposure group for 31.9%, high exposure group for 36.3%. 66 subjects (17.1%) had work-related respiratory symptoms. Atopy was observed in 132 subjects (34.2%) and positive skin prick test to wheat flour was observed in 32 subjects (8.3%).

Mean MBL level was 797.1±410.1 ng/ml in which the workers with work-related respiratory symptoms showed significantly higher level than those without it (899.0±468.2 vs. 769.0±389.8, p=0.019). After multivariate analysis, positive skin prick test to wheat flour and MBL level were the only statistically significant parameters for predicting work-related respiratory symptoms (p=0.001, p=0.008, respectively). A total of four polymorphism of MBL2 genes were significantly related to MBL level and haplotype 1 [GGAG], haplotype 2 [AGAC] were also significantly related to MBL level. No significant associations were found between MBL level and atopy, serum specific IgE and IgG4 antibodies. In vitro study, albumin increased MBL production in human lung epithelial cells, monocytes, and hepatocytes as dose-dependent manners.

Conclusion(s): The MBL, a component of innate immunity may contribute to develop work-related respiratory symptoms in bakery workers where the promoter polymorphisms of MBL2 gene could affect serum level of MBL.

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Not much new in the conclusion but read the first paragraph on approach.

Japan
ORAL IMMUNOTHERAPY FOR FOOD ALLERGY

Basic strategy for management of food allergy is to avoid the offending food for the security of diet. But the Japanese guidelines for food allergy recommend the policy of “minimal avoidance based on the precise diagnosis”. In other words, we are trying to instruct patients to “eat as much as possible”.

This policy has to be based on the result of an oral food challenge testing (OFC) to determine the safety level of allergen consumption for each patient. We have reported that these diet instructions were more effective on the earlier development of tolerance compared to the conventional food elimination. In other words, consumption of small amount of allergenic food promotes the natural outgrowth.
But patients with severe food allergies have the risk of anaphylaxis after eating trace amount of allergenic food. Oral immunotherapy (OIT) is targeting these patients not only for the achievement of tolerance, but more importantly, for the avoidance of unexpected severe reactions caused by an accidental exposure.

OITs are categorized into rush and slow protocols. Rush OIT has an induction phase to increase the allergen dose rapidly, which is conducted in-hospital setting for several days to weeks. Slow OIT is generally conducted at home to gradually increase the amount of allergen consumption for several months. Both protocols are followed by the maintenance phase to keep the tolerant dose.
Although many studies have reported considerably good results with 70 to 80 % of successful cases, no reports were free from concerns about safety. Even in the maintenance phase, severe reactions may be provoked in association with a sick or tired day, pollen season, irregular taking schedule, and exercise or bathing after consumption. For those safety reasons, OIT is still placed as an experimental trial, but is not recommended as a regular clinical practice.

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A unique milk sensitization and allergy.

Singapore
FOOD ALLERGY : ALLERGENCITY OF CARBOHYDRATES – UNIQUE PROBLEM IN DIFFERENT REGIONS

Our understanding that allergic responses to food are directed against mainly protein epitopes have recently been challenged. Recent studies demonstrates that IgE antibodies directed against carbohydrate moieties have been investigated in several studies in recent years.
This phenomenon has first been described against an oligosacharide galactose-alpha 1,3-galactose (alpha –gal) mainly in a geographical region that spanned the South Eastern parts of the United States since 2009. However awareness of this new clinical entity, has resulted in new cases identified in France and in Spain.

In Asia since 2009, there has been a series of cases following ingestion to a commercially manufactured prebiotic galacto-oligosacharide (GOS) that is found commonly in commercial milk formulas/beverages. The first reports from Vietnam suggests that the introduction of a new GOS containing beverage resulted in a spate of allergic reactions temporally associated with consumption of this beverage. We have seen in our Singapore a series of young children and adult presenting with anaphylaxis related to consumption of GOS containing commercial milk formulas. Interestingly, GOS is a functional food, and has been used as a supplemental prebiotic in food products and drinks in Europe and Japan since the 1980s, and was approved for supplementation in infant formula in Europe since December 2001. There has been no known reports of GOS containing beverages unlike the increased in allergic reactions associated with the arrival of these products to specific regions in Asia.

We present a novel concept of IgE mediated hypersensitivity to a unique carbohydrate GOS that appears to be have a distinct geographical footprint in Asia. The immunological data suggests that specific fractions of GOS (DP=degrees of polymerization) were more likely to induce basophil activation in-vitro. More studies need to be carried out to delineate the mechanisms as well as identify the primary sensitizer in this unique allergy.

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This only to note the marked rise of allergy, atopy, asthma in regions not normally associated with US, Europe, Australia. I think that it's been building remaining largely unacknowledged, untreated/undertreated.

Korea
GENETICS AND EPIGENETICS OF ALLERGY AND ASTHMA IN KOREAN CHILDREN

The prevalence of allergic diseases such as asthma, allergic rhinitis and atopic dermatitis has risen markedly in Korea, thus it is necessary to understand the etiologies, risk factors, and natural courses.

Over the last half century, lifestyle has changed and it has contributed to a considerable increase of allergic diseases in Korea. The lower prevalence of allergic diseases and atopy was associated with life styles such as farming, exposure to farm animals during pregnancy, breast feeding and older siblings. Also, the risk of current AR increased in subjects with GA or AA at IL-13(+2044) when they were exposed to mold in the home during infancy compared with subjects who have GG IL-13(+2044) and had not been exposed to mold. The hygiene hypothesis was adapted to the microbiota hypothesis, which proposed that lifestyle factors in early life alter the composition of the gut microbial flora, thereby affecting the development of mucosal immune tolerance. The synergistic risks between caesarean delivery, formula feeding, and antibiotic use affect on the prevaleces of asthma, allergic rhinitis and atopy. Additive analysis revealed that the adjusted odds ratio (aOR) of allergic rhinitis for subjects with the IL13 AG+AA genotype was highest when all three of early life factors were present. In addition, infants born by cesarean section had 2-fold higher odds of atopic dermatitis at 12 month of age than those born by vaginal delivery, and the infants with CD14 TC+CC genotype and cesarean section also showed higher risk to develop atopic dermatitis from COCOA birth cohort.

Renovation during prenatal period increased a risk of cord blood IgE response and AD at 1 year of age interacting with innate immunity and ROS related genes. Also, home remodeling during pregnancy may affect the development of atopic dermatitis through the epigenetic changes from the COCOA birth cohort study. These findings suggest that the environmental changes during pregnancy may affect the development of AD by the gene-environment interaction and epigenetic mechanism.

In summary, increase of allergic diseases in Korea may be originated from the multiple independent environmental risk factors in critical susceptible period and genetic susceptibility. In addition, gene and environment interaction or epigenetic change may be involved in the development of allergic diseases.

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Anaphylaxis to influenza vaccination confirmed not as related to egg allergy as believed prior to investigation. (Japan)

Japan
INFLUENZA VACCINE-INDUCED ANAPHYLAXIS: PIVOTAL ADVANCE IN IDENTIFICATION OF THE CAUSE

In the 2011/12 season, the incidence of influenza vaccine-associated anaphylaxis (IVA) was significantly higher than the average annual incidence in past years in Japan. IVA has been related to egg allergy since influenza vaccines are produced in embryonated eggs, however, most of the patients did not have egg allergy. We then investigated the cause of IVA by measuring specific IgE antibodies to various vaccine components and performing the basophil activation test (BAT). The “common belief” of egg protein-induced IVA was overturned by this novel approach.

Methods: We collected serum and blood specimens of IVA cases within 2 months after the events from all areas of Japan. The diagnosis was confirmed based on the Brighton collaboration case definition of anaphylaxis of level 1 and 2. Twenty cases of the confirmed IVA were examined and age-matched 15 healthy children and 8 egg allergy children with the similar vaccination history served as controls. Specific IgE to each component, namely A/H1, A/H3 and B, of the trivalent vaccines distributed for 2011-12 season from several vaccine manufacturers was measured with ELISA. Antigen-induced basophil activation was evaluated by measurement of CD203c expression with flowcytometry. Effects of additives in the vaccine preparations on the CD203c expression were also examined.

Results: Specific-IgE antibodies to A/H1, A/H3 and B were significantly elevated in patients with IVA than in controls. Influenza vaccine component-induced CD203c expression in basophils were also highly enhanced in IVA and no response was observed in control. Since the IVA cases segregated in patients who received phenoxyethanol-containing vaccines, effect of the preservative on basophil activation was examined and enhancement with phenoxyethanol, not with thimerosal, of the response was observed.

Conclusions: The results suggest that the recent IVA in Japan was caused by specific IgE antibodies to influenza vaccine components and that phenoxyethanol may have modified the reaction. Measurement of vaccine-component –specific IgE and BAT is useful for diagnosis of vaccine-associated anaphylaxis.

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This. Just... this.

China

ANAPHYLAXIS IN CHINA: TRIGGERS, CLINICAL FEATURES AND TREATMENTS
Background:

Anaphylaxis incidence is increasing. Little is known about the clinical features and triggers of anaphylaxis in China.

Methods:
We performed a review of clinical records for anaphylactic reactions over 10 years.

Results:
We identified 1008 anaphylactic reactions in 438 patients (222 male patients). 311 patients had recurrent reactions. The median age at time of the first reaction was 30 years (age range, 10 months to 70years). The skin (83.8%) was the most frequently affected organ followed by the respiratory system (68.6%) and cardiovascular system (56.3%). The triggers included food (79.2%), drugs (6.8%), insect (0.3%) and “others” (13.4%). Wheat was the culprit agent of food in 36.4% anaphylactic reactions. Traditional Chinese medicine (1.7%) was the most common cause of drug-induced anaphylaxis. 637(63.2%) reactions were managed in Emergency department, corticosteroid (26.6%) were more often administered than adrenaline (8.3%).Children were more often presented with respiratory symptoms compared with adults (80.1% vs. 64.9% P<0.001) .Fruits /vegetables were more common food triggers in children than in adults(16.5% vs.10.3% p=0.01) , whereas adults were more frequently sensitive to cereals compared with children (45.9% vs.34.5%,P=0.002) .Drug-induced anaphylaxis were more common in adults than in Children(8.2% vs.2.5%,p=0.003).

Conclusions:
The present study indicates that the most common symptoms of anaphylaxis in China were skin presentations. Respiratory presentations are more frequent in children. Food is the main trigger in anaphylaxis just as in the West, but shows a different picture, fruits /vegetables and cereals are common food triggers in children and adults respectively. Adrenaline is used in a minority of anaphylactic reactions.

And let me excise, bold and point in big Vegas neon lights to THIS:

Traditional Chinese medicine (1.7%) was the most common cause of drug-induced anaphylaxis.

Folks, if you listen to nothing else I say about FAHF-2 and TCM, it's this: they are drugs. Not all doctors dispensing it are equal. Not all sources are trustworthy. When I contextualize where, when, who and what with regard to pharmacognosy it's a necessary vetting process. It's why I crack the whip on distinguishing doctors with the profile of Dr. Li at Mr. Sinai and Dr. Jin-hui Dou at the FDA, from Herbal Pete at the corner shop.

Please note that while FAHF-2 is TCM as an herbal preparation TCM drug does not necessarily reference FAHF-2. TCM is a general term in English, even referenced as drugs, for herbal preparations. In this study TCM drugs means any herbal preparations, the majority are most likely used without issue but it is however the number one source of drug-induced anaphylaxis. That may be influenced by patient's desire to try it more often, could be a ton of factors.

But two main points 1) natural drugs are still drugs there's no safety inherent because it's TCM 2) FAHF-2 is TCM drug (herbal prep), but not all TCM drug (herbal prep) is FAHF-2. I highly doubt any of the anaphylaxis induced in this study was anything but formulas for a wide array of maladies.

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As I write this post the presentation at this very time is transcutaneous sensitization, without eating food eczema provides pathway from air to body. Whether or not that's old news I dunno. But there's a fancy slide and a guy in a podium in front of it.

Also, for travel to Singapore, Taiwan, some parts of China we may have a working list of clinicians seeing patients including pediatric. I'm starting to think for many regions the only epinephrine you can count on is what you bring with you in country. Period.

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Part of the ACAAI presentation tomorrow includes a proposal to move towards component testing in place of whole protein. Also to place greater emphasis on atopy... in general to move towards granular, individual approach?