New Science

Link Between Father Smoking Before Conception and Child’s Asthma Research presented at the European Respiratory Society (ERS) International Congress in Munich is the first study in humans to analyze the link between a father’s smoking habits before conception and a child’s asthma. The findings add to growing evidence from animal studies which suggest that the father’s exposures before parenthood can harm his child. The study analyzed the smoking habits of over 13,000 men and women via a questionnaire. The researchers analyzed the link in both mothers and fathers and looked at the number of years a person had smoked prior to conception, the incidence of asthma in children and whether the parent had quit before the baby was conceived. Previous research showed that a grandmother’s smoking could induce epigenetic changes that predisposed grandchildren to asthma.

Herbal-Based Anti-Malaria Drug May Help Treat Asthma Singapore researchers led by Associate Professor Fred Wong from the Department of Pharmacology at the NUS Yong Loo Lin School of Medicine, discovered that artesunate, a common herbal-based anti-malarial drug, can be used to control asthma, with better treatment outcomes than other drugs currently available. The team revealed for the first time that artesunate is able to suppress airway inflammation and produce an array of anti-inflammatory effects similar to those by dexamethasone, the most potent steroid currently available, and with less side effects. This breakthrough discovery was first published in the journal Metabolomics on 16 July 2014. More

Lung Drugs Affected by Time of Day (Science Daily) Research, led by Professors David Ray and Andrew Loudon from The University of Manchester, found out that cells lining the lung airways have their own body clock which is the time-keeper for lung inflammation — both conditions cause swelling (inflammation) in the lungs. And the team discovered that more severe lung inflammation happens as a result of the loss of the body clock working in these cells. Professor Loudon said: “We found a key molecule known as CXCL5 that facilitates lung inflammation which is a key regulator of how immune cells get into tissues. The loss of CXCL5 completely prevents the time of day regulation of lung inflammation which opens up new ways to treat lung diseases.” More

New Drug Shows Promise for Atopic Dermatitis “An investigational medication shows promise in treating the most common skin disorder, often referred to as eczema or atopic dermatitis, according to a study published July 9 in the New England Journal of Medicine. The findings could eventually bring significant relief for many who suffer intense itching and other troubling features of atopic dermatitis, according to the study’s lead author Lisa A. Beck, M.D., professor of Dermatology and Medicine at the University of Rochester Medical Center. The drug, dupilumab, blocks the action of two proteins involved in inflammation, interleukin-4 and interleukin-13, which play a key role in atopic dermatitis (AD). AD is a common skin disease with troubling signs that include severely dry skin, red lesions that may crust or ooze, skin thickening, and symptoms of intense itching that may lead to skin wounds, infections and sleep disturbance.” More

Interferons Key to Blocking Allergic Immune Function? (Science Daily June 16, 2014) “A mechanism that could underlie the development of cells that drive asthma and allergies has been uncovered by immunology researchers at UT Southwestern Medical Center. Asthma and allergies are both driven by an inappropriate activation of the immune system, primarily a subtype of white blood cells known as T helper 2 cells, or Th2 cells. These cells are normally responsible for defense against parasites, but are also the main culprits behind the symptoms of asthma and allergies.

“Dr. David Farrar, Associate Professor of Immunology and Molecular Biology at UT Southwestern, and his team found that the antiviral molecules known as type I interferons (IFNs) block the development of these allergy- and asthma-driving Th2 cells. ‘The fact that interferon could stop the activation of these harmful cells was of particular interest because interferons are already approved by the Food and Drug Administration for the treatment of other diseases, such as multiple sclerosis and hepatitis,’ said Dr. Farrar.” More.

Novel Antibody Treatment for Asthma
Researchers at St. Joseph’s Healthcare Hamilton and McMaster University have successfully tested an antibody that can improve the quality of life for individuals with asthma by relieving inflammation in the lungs. The research was led by Dr. Gail Gauvreau, associate professor at McMaster University. The study was published in the New England Journal of Medicine and presented at the American Thoracic Society conference in San Diego. It concluded that blocking a specific protein in the lungs with an antibody both alleviates baseline inflammation and provides resistance to allergens for those with mild allergic asthma.
“It was known that the epithelial cells which line the airways in the lungs produce a protein called thymic stromal lymphopoietin (TSLP) that causes inflammation. This study, for the first time, proved that these cells continually produce this protein in humans with asthma,” states O’Byrne. “While we studied patients with allergic asthma, this research opens the door for the development of new treatments not only for this population, but for those diagnosed with severe asthma as well.”
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New Epidemiology Model Combines Multiple Genomics Data “The difference between merely throwing around buzzwords like ‘personalized medicine’ and ‘big data’ and delivering on their medical promise is in the details of developing methods for analyzing and interpreting genomic data. In a pair of new papers, Brown University epidemiologist Yen-Tsung Huang and colleagues show how integrating different kinds of genomic data could improve studies of the association between genes and disease.

“The kinds of data Huang integrates are single-nucleotide differences in DNA, called SNPs, data on gene expression, which is how the body puts genes into action, and methylation, a chemical alteration related to expression. All are potentially relevant to whether a person gets sick, but most analyses that connect genomics to disease account for only one. In papers now online in the journals Biostatistics andAnnals of Applied Statistics, Huang describes the results of testing the model in analyses of asthma and brain cancer data.

“‘Our integrated approach outperforms single-platform approaches,’ Huang said. ‘Applied to real data sets, it works.’”

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No More Mice for Allergy, Asthma Research? English scientist have developed a “3-D” methodology for testing the effectiveness of allergy drugs that may let the little furry creatures off the hook. A team at the University of Nottingham writes in Molecular Pharmaceutics: “Although some human-cell-based assays exist, they are usually 2D, consist of single cell type, and have limited cellular and functional representation of the native tissue. In this study, we have used biomimetic porous electrospun scaffolds to develop an immunocompetent 3D model of the human respiratory tract comprised of three key cell types present in upper airway epithelium. The three cell types, namely, epithelial cells (providing a physical barrier), fibroblasts (extracellular matrix production), and dendritic cells (immune sensing), were initially grown on individual scaffolds and then assembled into the 3D multicell tissue model. The epithelial layer was cultured at the air–liquid interface for up to four weeks, leading to formation of a functional barrier as evidenced by an increase in transepithelial electrical resistance (TEER) and tight junction formation. The response of epithelial cells to allergen exposure was monitored by quantifying changes in TEER readings and by assessment of cellular tight junctions using immunostaining. It was found that epithelial cells cocultured with fibroblasts formed a functional epithelial barrier at a quicker rate than single cultures of epithelial cells and that the recovery from allergen exposure was also more rapid.” More.

Enzyme Appears to Govern Allergy Symptoms
Science Daily March 7 Ohio State researchers are looking at an enzyme that helps maintain immune system function by “throwing away” a specific protein has a vital role in controlling symptoms of allergic asthma in mice. The finding suggests the enzyme could be a target for drugs used to treat allergic asthma.

More Allergic Blowback from Antibiotics
Antibiotics have been implicated for contributing to allergic diseases by destroying useful gut bacteria as well as pathogenic ones, but a new study indication a possible additional problem. Antibiotic treatment was seen to induce gut fungal overgrowth, which promoted allergic airway inflammation. More.

Pivotal Cellular Protein Underlying Eczema Identified
Science Daily Jan. 9, 2014 — Researchers from the La Jolla Institute for Allergy and Immunology have revealed a critical player in the cellular interactions leading to eczema. In a study, Toshiaki Kawakami, M.D., Ph.D., and his research team provide information supporting the long-held theory that mast cells are key contributors to eczema, also known as atopic dermatitis. They also showed that a cellular protein, known as STAT5, triggers major increases in mast cells in some patients, raising the possibility that new therapies could be based on blocking STAT5 in mast cells. The studies used skin samples from eczema patients. “We found that the number of mast cells, which we have previously shown to be important in mouse atopic dermatitis, is increased in human patients,” says Kawakami. “We also showed that these mast cells contain high levels of the active form of STAT5.”

Kawakami says this finding is a continuation of his nearly 10-year effort to pinpoint the cascade of key cellular actions involved in eczema. Initially working in mice, his latest study enabled human confirmation of his key findings. “We now know that, in eczema, the mechanisms we found in mice are also operative in human disease,” says Kawakami. Along with showing that mast cells and STAT5 drive the eczema process in humans, this study also found an enzyme — Phospholipase C-beta3 (PLC-?3) — that can block the activation. PLC-?3 has a calming effort on STAT5 and can prevent it from driving up the mast cell numbers, explains Kawakami. “The mast cell numbers are inversely correlated with PLC-?3 levels,” he says. “The more PLC-?3, the fewer the mast cells.” More

Odor Receptors in Lungs May Help Trigger Asthma Attacks
Science Daily Jan. 2, 2014
“Scientists at Washington University in St. Louis and the University of Iowa have showed that your lungs have odor receptors as well…. Unlike the receptors in your nose, which are located in the membranes of nerve cells, the ones in your lungs are in the membranes of neuroendocrine cells. Instead of sending nerve impulses to your brain that allow it to ‘perceive’ the acrid smell of a burning cigarette somewhere in the vicinity, they trigger the flask-shaped neuroendocrine cells to dump hormones that make your airways constrict…The newly discovered class of cells expressing olfactory receptors in human airways, called pulmonary neuroendocrine cells, or PNECs, were found by a team led by Yehuda Ben-Sharar, PhD, assistant professor of biology and medicine at Washington University in St. Louis, and including colleagues Steven L. Brody and Michael J. Holtzman of the Washington University School of Medicine, and Michel J. Welsh of the Lucille A. Carver College of Medicine at the University of Iowa.”
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Smoking Affects Molecular Mechanisms, Children’s Immune Systems
Science Daily Oct. 7, 2013 — The Leipzig Helmholtz Center for Environmental Research has gained new insights on the influence of tobacco smoke in utero. For the first time, it could be demonstrated with smoking pregnant women and their children, how exposure to tobacco smoke affects the development of human immune system on molecular level. The focus thereby was on microRNA — a short, single-stranded RNA molecule that is now recognised as playing an important role in gene regulation…As part of the long-term study LINA, environmental immunologists from Leipzig have been focussing on tobacco smoke as an environmental stressor. The main objective for Dr Gunda Herberth was to reveal the influence of tobacco smoke on the development of children’s immune systems — at molecular level. From the results that were recently published in the Journal of Allergy and Clinical Immunology, one thing is certain: “For the first time we were able to describe the effect of prenatal environmental stressors on the regulation of microRNA.”
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Explanation for Increased Asthma Severity in Children Exposed to Diesel Exhaust from Traffic
Science Daily Sep. 23, 2013 — A new study shows that exposure to diesel exhaust particles from traffic pollution leads to increased asthma severity in children. Moreover, the study finds that this is due to increased blood levels of IL-17A, a protein associated with several chronic inflammatory diseases, in children with high diesel exposure.

The study by researchers at Cincinnati Children’s Hospital Medical Center is published online in the Journal of Allergy and Clinical Immunology. The research, conducted in mice and in humans, showed that neutralizing IL-17A prevented airway inflammation. Neutralization of IL-17A “may be a useful potential therapeutic strategy to counteract the asthma-promoting effects of traffic-related air pollution, especially in highly exposed, severe allergic asthmatics,” says Gurjit Khurana Hershey, MD, PhD, director of asthma research at Cincinnati Children’s and senior author of the study.

“Blocking IL-17A may be a useful strategy to counteract the effects of traffic-related air pollution, especially in highly exposed allergic asthmatic children,” says Dr. Hershey.
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Eosinophils Misunderstood? Study Points to New Direction for Research
Science Daily Sep. 16, 2013 — A new link between meal times and daily changes in the immune system has led UC San Francisco researchers to question standard assumptions about the roles of eosinphils, a white blood cell of that is thought to fight parasitic worms. It might actually help the invaders, according to Richard Locksley, MD, professor of medicine at UCSF and the senior author of the new study, published online on Sept. 15 in Nature.

Locksley’s team found in mice that a type of rare immune cell serves as a link between nerve-signaling during meals and the regular expansion of a specific white blood cell population, called eosinophils, that ebbs and flows in the gut. The natural function of eosinophils in the gut and elsewhere in the body is an open question, Locksley said, despite the longstanding belief in medicine that the cells play an important role in fighting parasitic diseases. “Maybe we don’t really know what eosinophils are doing in infection and in allergic reactions, because we don’t even know yet what they do normally,” Locksley said.
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Study Sheds New Light on Gut Microbe Links to Atopic Dermatitis
The Journal of Allergy and Clinical Immunology
Volume 132, Issue 3 , Pages 601-607.e8, September 2013
A group of European scientists (John Penders, PhD et al) “examined the influence of environmental determinants on the establishment of the infant microbiota composition and subsequently investigated the role of this microbiota composition in association with the development of AD.”
Although almost all children in our study were breast-fed, they found large differences in the microbiome composition, at the age of 31 weeks, of infants who were breast-fed for more than 6 months compared with infants who were breast-fed less. They note that while formulas have become supplemented with compounds to mimic human milk as much as possible, many bioactive compounds in breast milk, “including immunoglobulins, cytokines, hormones, enzymes, and microbes” remain absent from formulas.

Further, Cesarean delivery decreases long term the colonization rate of bacteroides and increase clostridia, including C difficile, that persisted over time. Next-generation sequencing confirms that vaginal-delivered infants acquired bacterial communities resembling their own mothers’ vaginal microbiota, but C-section babies had gut bacteria “that were most similar to those found on the skin surface. While much of the research confirms older studies, the scientists claim, “[W]e report for the first time a dose-response relationship between birth order and microbiota composition, which lends further support to a causal relationship. The only association between gut microbiota composition and the risk of AD development was the positive association between Clostridium cluster I prevalence (at ages 5 and 13 weeks) and AD.”

They conclude: “[T]he indigenous microbiota composition is likely to be one of the underlying mechanisms explaining the birth order effect in the cause of allergies. Future research is especially needed to understand how infants sample their environment over time (eg, whether, when, and to what extent exchange of microorganisms from older siblings to newborns contributes to the establishment of their microbiome), and if this relates to the risk of developing allergies and atopic manifestations such as AD.”

JACI editors say, “Using mediation analysis, the authors demonstrated that the microbiota composition is likely to be one of the underlying mechanisms explaining the birth order effect in the cause of allergies. These results strengthen the evidence for a causal pathway and provide new leads for the primary prevention of allergies by modulating the gut microbiota.”

Skin Cell Defect Is Surprising Allergy Trigger: Skin and Food Allergies Can Be Result of Skin Cell ‘Glue’ Deficiency
Science Daily Aug. 26, 2013 — “In a new study published in Nature Genetics, Northwestern Medicine and Tel Aviv University scientists have found that a structural defect in skin cells can contribute to allergy development, including skin and food allergies, traditionally thought primarily to be a dysfunction of the immune system. The finding is related to the team’s identification of a new rare genetic disease, called “severe dermatitis, multiple allergies, and metabolic wasting,” or SAM, caused by mutations in the molecule desmoglein 1.”
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Canadian researchers funded to develop paper-based biosensor to measure asthma marker
Dr. Parameswaran Nair and Dr. John Brennan of McMaster University have received a $600,000 award to develop a bioactive paper that aims to provide an inexpensive, point-of-care diagnostic tool for asthma and COPD. The paper strip will measure the quantity of an eosinophil-specific protein secreted in sputum. Treatment strategies for asthma and COPD that are based on quantitative eosinophil cell counts provide significantly better outcomes than strategies guided by conventional assessments of symptoms and airflow.

NSERC and CIHR have provided $600,000 over a period of three years through the Collaborative Health Research Program to further Dr. Nair’s research on the biosensor.
Dr. Nair, an AllerGen Investigator, is the CIHR Canada Research Chair in Airway Inflammometry and Associate Professor of Medicine at McMaster University. Dr. Brennan is a Canada Research Chair in Bioanalytical Chemistry and the Director of McMaster’s BioInterfaces Institute.
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Genetic Glitch at the Root of Allergies Revealed
Science Daily July 24, 2013 — Newly published research by investigators at Johns Hopkins Children’s Center and the Johns Hopkins Institute of Genetic Medicine reveals that a faulty genetic pathway already known for its role in some connective tissue disorders is also a potent player in many types of allergies. Scientists have long understood that allergies are the result of a complex interplay between environment and genes, but now, in what investigators believe is a scientific first, a single genetic pathway has been implicated in an array of allergic disorders. A report on the study’s findings, published July 24 in Science Translational Medicine, shows that aberrant signaling by a protein called transforming growth factor-beta, or TGF-beta, may be responsible for disrupting the way immune cells respond to common foods and environmental allergens, leading to a wide range of allergic disorders.
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Basophils and Eosinophilic Esophagitis Linked in New Study
As reported in Science Daily and Nature Medicine, a new study from at the University of Pennsylvania Medical School and The Children’s Hospital of Philadelphia (CHOP) shows that an interaction of basophils, an immune cell, and specific reactions to allergenic foods may team up to cause eosinophilic esophagitis EoE.

Building on work showing a connection between mutations in the gene that encodes for thymic stromal lymphopoietin (TSLP), a protein that is produced by epithelial cells that line the esophagus and directs the activities of various types of immune cells, and EoE in children, David Artis, PhD, associate professor of Microbiology at Penn, two postdoctoral researchers in the Artis lab, Mario Noti, PhD and Elia Tait Wojno, PhD, and colleagues, have identified one mechanism by which TSLP might contribute to the development of EoE. They describe their work this week online ahead of print in Nature Medicine.

Using a mouse model of EoE, Artis’s group found that sensitization to egg and peanut protein, in association with increased levels of TSLP, mobilizes basophils, which in healthy people, comprise less than 1 percent of the total immune cells in the body. Basophils are the “effector cells” that are responsible for late-phase reactions to food allergens. When mice with EoE were treated with therapeutic reagents that limited TSLP and basophil responses to food allergens, esophageal inflammation in these animals improved dramatically.

“The findings from both mouse and human studies suggest that TSLP and basophils may promote the development of inflammation in the esophagus in response to foods that trigger an allergic response in some individuals, or that TSLP and basophils could contribute to the persistence of inflammation. These factors could potentially be targeted using novel therapeutics to treat EoE in patients, say the researchers.”
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Link to Food Allergy Through the Skin?
FRIDAY, July 19 (HealthDay News) — The breakdown in the skin barrier that occurs in eczema could play a key role in triggering food sensitivity in babies, the researchers from King’s College London and the University of Dundee said. “This is a very exciting study, providing further evidence that an impaired skin barrier and eczema could play a key role in triggering food sensitivity in babies, which could ultimately lead to the development of food allergies,” Dr. Carsten Flohr, of King’s College London, said in a college news release.

The researchers said the discovery suggests that food allergies may develop via immune cells in the skin rather than in the gut and that the findings indicate that eczema may be a potential target for preventing food allergies in children. A link between eczema and food allergies has been known for some time, but this study — published July 18 in the Journal of Investigative Dermatology — adds to growing evidence of the skin barrier’s role in the process, according to the researchers. “This work takes what we thought we knew about eczema and food allergy and flips it on its head. We thought that food allergies are triggered from the inside out, but our work shows that in some children it could be from the outside in, via the skin,” Flohr explained. “The skin barrier plays a crucial role in protecting us from allergens in our environment, and we can see here that when that barrier is compromised, especially in eczema, it seems to leave the skin’s immune cells exposed to these allergens.”
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Genetic Associations Found In Pollen, Dust And Cat Allergies
Sixteen new genetic associations, including pollen, dust-mite and cat allergies, have been identified by the largest genome-wide association study ever conducted on common allergies. 23andMe, the leading personal genetics company, and the Avon Longitudinal Study of Parents and Children (ALSPAC) collaborated on the study, which examined data for more than 53,000 individuals.

The study, published in Nature Genetics, also identified eight genetic variations for allergies that have previously been associated with asthma. A series of key pathways in the biological basis of common allergies are highlighted by the genes implicated in the study. “We’ve seen some substantial increases in prevalence of allergies and asthma,” said David Hinds,PhD, 23andMe principal scientist. “Although environmental factors certainly play a role, our study reinforces the genetic link between common allergens and a person’s susceptibility to experiencing an allergic reaction. Additionally, current estimates of the heritability of allergies are high, which suggests that understanding the genetic factors underlying allergic conditions may be key to understanding who might be most likely to suffer from allergies and how the condition might best be treated.”
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Duke research advances towards a genetic test to predict if children will outgrow their asthma
The study, published in the 28 June online issue of The Lancet Respiratory Medicine, says about half of children grow out of their asthma by the time they reach their teen or adult years. For this latest study, the researchers looked at the results of a huge genetic study, drafted a profile of asthma risk genes and tested it against a leading asthma research database of individuals that have been followed from birth to their 30s.

The predictions made in the study “are not sufficiently sensitive or specific to support their immediate use in routine clinical practice,” lead author Daniel Belsky, a National Institute on Aging Postdoctoral Fellow at Duke University Center for the Study of Aging and Human Development.  “As additional risk genes are discovered, the value of genetic assessments is likely to improve,” says Belsky. More

Exposure to Allergens on Skin Makes Baby Mice Vulnerable to Food-Induced Anaphylaxis
As reported in the February issue of the Journal of Allergy Asthma and Clinical Immunology, Boston researchers sensitized mice “by repeated application of ovalbumin (OVA) to tape-stripped skin over 7 weeks or orally immunized with OVA and cholera toxin (CT) weekly for 8 weeks and then orally challenged [them] with OVA. Body temperature was monitored, and serum mouse mast cell protease 1 levels were determined after challenge. Tissue mast cell (MC) counts were examined by using chloroacetate esterase staining. Levels of serum OVA-specific IgE and IgG1 antibodies and cytokines in supernatants of OVA-stimulated splenocytes were measured by means of ELISA. Serum IL-4 levels were measured by using an in vivo cytokine capture assay.”

They concluded: “Epicutaneously sensitized mice, but not mice orally immunized with antigen plus CT, have expansion of intestinal MCs and IgE-mediated anaphylaxis after single oral antigen challenge. IgE is necessary but not sufficient for food anaphylaxis, and MC expansion in the gut can play an important role in the development of anaphylaxis.”

Eczema Linked to Immune Defense Against Ticks
(Apr. 21, 2013) — Allergies have long been associated with the body’s defenses against parasites. Now Australian researchers have found a possible connection between eczema and invasive organisms. According to Science Daily “Sydney researchers have discovered a new type of immune cell in skin that plays a role in fighting off parasitic invaders such as ticks, mites, and worms…”

“The new cell type is part of a family known as group 2 innate lymphoid cells (ILC2) which was discovered less than five years ago in the gut and the lung, where it has been linked to asthma. But this is the first time such cells have been found in the skin, and they are relatively more numerous there. ‘Our data show that these skin ILC2 cells can likely suppress or stimulate inflammation under different conditions,’ says Dr Ben Roediger, a research officer in the Immune Imaging Laboratory at Centenary headed by Professor Wolfgang Weninger. ‘They also suggest a potential link to allergic skin diseases.’”

The findings have been published in the journal Nature Immunology.
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Bitter-Tasting Foods May Provide Help in Relaxing Asthma-Constricted Airways
(Science Daily 3/5/13) An interdisciplinary team of scientists at the University of Massachusetts Medical School headed by Ronghua ZhuGe, PhD, associate professor of microbiology and physiological systems have taken a step forward in understanding how the substances that give some foods their bitter flavor also act to reverse the contraction of airway cells, a process known as bronchodilation. This effect may one day be harnessed to provide improved treatments for airway obstructive diseases such as asthma and chronic obstructive pulmonary disease.

Most humans experience five types of tastes: sweet, salty, sour, bitter and savory. Bitter taste receptors most likely evolved to help alert the body to potentially harmful foods that have spoiled or are toxic. The receptors have long been thought to only exist in certain cells present in the tongue. Over the last few years, however, scientists have come to realize that these receptors are present in many other cells throughout the body. Specifically, bitter taste receptors on smooth muscle cells in the airway act to relax the cells when exposed to bitter-tasting substances. The fact that bitter substances can relax these smooth muscle cells suggests that they may have the potential to halt asthma attacks and in fact could even be an improvement over current treatments since the relaxation effects are quite fast. Indeed, experiments in mice suggest that the effects are stronger.
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Reports on Molecule That May Play Role in Stopping Asthma
(Science Daily) Feb. 27, 2013 — Scientists from Brigham and Women’s Hospital are on the brink of the next treatment advancement that may spell relief for the nearly nineteen million adults and seven million children in the United States suffering from asthma. The scientists discovered two new drug targets in the inflammatory response pathway responsible for asthma attacks.

Researchers studied the lungs and blood of 22 people with mild and severe asthma. They saw that immune cells called natural killer cells and type 2 innate lymphoid cells played significant roles in airway inflammation. Natural killer cells decreased airway inflammation by encouraging programmed cell death in eosinophils, whereas type 2 innate lymphoid cells promoted airway inflammation by secreting cell-signaling molecules called interleukin-13.
Both mechanisms were controlled by a molecule called lipoxin A4 which is responsible for resolving inflammation. The researchers saw that lipoxin A4 encouraged natural killer cells to decrease inflammation by facilitating eosinophil cell death. Lipoxin A4 also discouraged type 2 innate lymphoid cells from promoting inflammation by blocking interleukin-13 secretion.

“Stopping airway inflammation is similar to putting out a forest fire,” said Bruce Levy, MD, Pulmonary and Critical Care Medicine Division, BWH Department of Internal Medicine, senior study author. “Firefighters tackle forest fires in two ways — dousing the fire with water and clearing away dry brush that could fuel the fire. Lipoxin A4 does just that to resolve inflammation. It is an airway inflammation fighter that performs the double duty of dampening pathways that ignite inflammation while at the same time clearing away cells that fuel inflammation.”
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Air Pollutants From Many Sources Seriously Impair T-Regulatory Cells
SAN ANTONIO –New research by Dr. Kari Nadeau of Stanford ties air pollutants called polycyclic aromatic hydrocarbons, or PAHs, the products of incomplete burning of fuel in diesel engines, furnaces, wood fires, wildfires and even barbeque grills to poorly functioning T-regulatory cells, or T-regs, which normally ratchet down immune-caused inflammation as needed. “T-regs are peacekeeper cells,” says Kari Nadeau, a physician and biochemist at Stanford University, who presented the findings February 23 at a meeting of the American Academy of Allergy, Asthma and Immunology. “But in asthma, T-regs are impaired.”

The researchers used airborne PAH sampling to estimate exposure to PAHs, and chose Fresno because of its relatively high air pollution levels. It was also the locale for previous research on asthma; the city has the second-highest levels of particulates in the U.S.

Nadeau also reported that consistent PAH exposure coincided with changes in a gene called Foxp3. As reported in Nature in 2010, Foxp3 seems to be a master regulator of T-reg populations in the body. Unfortunately, Nadeau says, the changes observed in the Foxp3 gene seem irreversible and widespread.
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Nanotechnology Against Pollen Allergy
Feb. 11, 2013 — Science Daily reports that Berlin researchers have now been able to identify the grass pollen molecule, against which the allergic response of hay fever in children is initiated. In addition, it was shown that the first individual antibodies generated in children against individual pollen molecules can be identified even before the initial symptoms of a pollen allergy are developed.

Plan B for Allergy Attacks? Mechanism found for destruction of key allergy-inducing complexes, Stanford researchers say
Researchers have learned how a man-made molecule destroys complexes that induce allergic responses — a discovery that could lead to the development of highly potent, rapidly acting interventions for a host of acute allergic reactions. The study, published online Oct. 28 in Nature, was led by scientists at the Stanford University School of Medicine and the University of Bern, Switzerland. The new inhibitor disarms IgE antibodies, pivotal players in acute allergies, by detaching the antibody from its partner in crime, a molecule called FcR. (Other mechanisms lead to slower-developing allergic reactions.)
The key to actively disabling the allergic response lies in the separation of IgE from the FcRs on the surface of mast cells. But separating these dangerous couples is a tall order because their interaction is extremely stable — sensitizing the mast cells for weeks. Currently available treatment using omalizumab (an anti-IgE antibody sold under the trade name Xolair) can block new interactions between IgE and FcR, but it is not designed to pry the molecules apart once they’ve formed a bond on the surface of a mast cell. So Xolair can dampen the allergic response, but as stated on the product’s website: “Xolair is not a rescue medicine and should not be used to treat sudden asthma attacks.”
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New Clues Into How to Treat Eczema
ScienceDaily (Oct. 11, 2012) — “More than 15% of children suffer with eczema, or atopic dermatitis, an inflammatory skin disease that in some cases can be debilitating and disfiguring. Researchers reporting in the October issue of Immunity have discovered a potential new target for the condition, demonstrating that by blocking it, they can lessen the disease in mice.

“In eczema, immune T cells invade the skin and secrete factors that drive an allergic response, making the skin itch. Dr. Raif Geha, of Boston Children’s Hospital, and his collaborators now show that scratching the skin precipitates the condition by encouraging an influx of other immune cells called neutrophils. These neutrophils secrete a lipid called leukotriene B4 that calls in more neutrophils, and more importantly, potent immune T cells that are the hallmark of eczema. These cells cause inflammation that aggravates the skin further. The investigators suspected that blocking the onslaught of these cells might slow down the disease or even stop it in its tracks.”
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Blocking Biological Responses to Airway Smooth-Muscle Contractions, Secretions May Help with Asthma ScienceDaily (Sep. 17, 2012) — A new study that identifies ways to reduce the factors that lead to an asthma attack gives hope to asthma sufferers. A UCSF researcher and his colleagues believe they have found a way to help asthma sufferers by impeding the two most significant biological responses that lead to an asthma attack.

In a paper published September 17 in the Proceedings of the National Academy of Sciences (PNAS), researchers from UCSF, Johns Hopkins University and Duke University demonstrate that a specific calcium-activated chloride channel holds valuable clues to reducing two biological processes that contribute to the severity of asthma. These channels regulate airway secretions and smooth muscle contraction, the two major factors that lead to an asthma attack. “Maybe if we could inhibit both of these processes by blocking this one channel, then we could affect the two symptoms of asthma,” said senior author Jason Rock, PhD, assistant professor at the UCSF Department of Anatomy.
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Researchers Develop New Class of Non-Steroidal Anti-Inflammatory Drug that Could Reduce Allergies, Asthma, Other Diseases with Fewer Side Effects
ScienceDaily (Sep. 6, 2012) — A synthetic, anti-inflammatory and anti-allergic family of drugs to combat a variety of illnesses, while avoiding detrimental side effects, has been developed by a Hebrew University of Jerusalem researcher, Saul Yedgar.

Inflammatory/allergic diseases affect different organs, such as the skin inflammations (dermatitis, psoriasis); airway injury and allergy (asthma, cystic fibrosis, allergic rhinitis); osteoarthritis and rheumatoid arthritis; intestinal inflammation (ulcerative colitis, Crohn’s disease); central nervous system inflammation (multiple sclerosis), as well as atherosclerosis and cancer metastasis.  All share biochemical mechanisms, significantly, the action of an enzyme family (PLA2) that initiates the production of a cascade of pro-inflammatory mediators.

“In Prof. Yedgar’s lab at the Hebrew University, he and his associates have designed and constructed an entirely novel synthetic generation of drugs that control the PLA2 activity and the subsequent cascade of pro-inflammatory mediators, thereby providing multi-functional, anti-inflammatory drugs (MFAIDs).

“MFAIDs [Multi-Functional Anti-Inflammatory/anti-Allergic Drugs] have shown excellent safety and were found efficient in treating diverse inflammatory/allergic conditions in animal models, using different ways of administration — oral, rectal, intravenous, inhaled and injected. These conditions included sepsis, inflammatory bowel diseases, asthma and central nervous system inflammation.”
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Gastric Bacterium Helicobacter Pylori Protects Against Asthma
ScienceDaily (July 1, 2011) — Infection with the gastric bacterium Helicobacter pylori provides reliable protection against allergy-induced asthma, immunologists from the University of Zurich have demonstrated in an animal model together with allergy specialists from the University Medical Center of the Johannes Gutenberg University Mainz. Their results published in the Journal of Clinical Investigation confirm the hypothesis recently put forward that the dramatic increase in allergic diseases in industrial societies is linked to the rapid disappearance of specific micro-organisms that populate the human body.

In an article published in the Journal of Clinical Investigation, scientists from the University of Zurich and the University Medical Center of the Johannes Gutenberg University Mainz now reveal that the increase in asthma could be put down to the specific disappearance of the gastric bacterium Helicobacter pylori (H. pylori) from Western societies. H. pylori is resistant to gastric acid. According to estimates, around half of the world’s population might be infected with the bacteria. The affliction often has no symptoms, but under certain conditions can cause gastritis, gastric and duodenal ulcers, and stomach cancer. Consequently, H. pylori is often killed off with antibiotics as a precaution, even if the patient does not have any complaints.
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Rewiring DNA Circuitry Could Help Treat Asthma
ScienceDaily (July 5, 2012) — Reprogramming asthma-promoting immune cells in mice diminishes airway damage and inflammation, and could potentially lead to new treatments for people with asthma, researchers have found. The researchers were able to reprogram the asthma-promoting cells (called Th2 (T-helper 2) cells) after identifying an enzyme that modifies the DNA of these cells. The enzyme could be a target for the development of new treatments for chronic inflammatory diseases, in particular allergic asthma, caused by an excess of Th2 cells.

Walter and Eliza Hall Institute researcher Dr Rhys Allan led the research while working at Institut Curie, Paris. The research team from Institut Curie, National Centre for Scientific Research (CNRS), France, National Institute of Health and Medical Research (INSERM), France, and Montpellier Cancer Research Institute published the study July 4 in the journal Nature.

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New York-area adults with celiac disease are needed for a research study!
The Celiac Disease Center at Columbia University is testing a new automated phone survey to measure symptoms of celiac disease that can be used to test new treatments for celiac disease.
Looking for people with biopsy-proven celiac disease to test the new survey while eating a food with or without a small amount of gluten. Participants will take the survey every day for 8 weeks and will come to the Celiac Disease Center at Columbia University 5 times during the study. You will be compensated for your time.
This study is being sponsored by Alvine Pharmaceuticals.
If you are interested in learning more, please contact:
Maria Teresa Minaya (Study Coordinator)
Celiac Disease Center at Columbia University
180 Fort Washington Ave Suite 936
New York, NY, 10032
Email: celiaccentercolumbiaresearch@columbia.edu

New Study Shows How Immune System May Get Sidetracked Resulting in Allergies, Autoimmune Disease
ScienceDaily (May 27, 2012) — Newfound details of the immune system suggest a role for never-before-considered drug classes in the treatment of allergic and autoimmune diseases, according to a University of Alabama at Birmingham study published online May 27 in Nature Immunology. The results advance the current understanding of the way the body’s initial, vague reaction to any invading organism expands into a precise and massive counterattack. That expansion starts when a dendritic cell “swallows” a piece of any invader encountered, ferries it to the nearest lymph node and presents it there for notice by lymphocytes, the workhorse cells of the immune system. According to the current model, dendritic cells first must encounter T lymphocytes in the paracortex, or T cell zone, within the node. Only there will the interaction enable lymphocytes to expand into an army of clones primed to attack the invader.

To the research team’s great surprise, the data showed that, although immune response works this way during viral flu infections, it is not always the case. When the body is infested with parasitic worms, for instance, dendritic cells link with T cells near B lymphocytes, under the control of B cell-related signals and outside the T cell zone. “Considering that diseases from asthma to lupus can occur because the system mistakenly ramps up the same types of T cell responses it normally uses against worms, our finding that B lymphocytes control the T cell/dendritic cell interactions that trigger such responses has important, practical implications,” said Frances Lund, Ph.D., chair of the UAB School of Medicine’s Department of Microbiology and corresponding author. “The field now has cause to look at several experimental and existing drugs known to interrupt B cell signals as potential treatments for diseases driven by T cells.”
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Researchers Find Link Between Medications and Serious Drug Allergies
A team led by the University of Melbourne and Monash University, Australia, has discovered why people can develop life-threatening allergies after receiving treatment for conditions such as epilepsy and AIDS. The study published in the journal Nature, revealed how some drugs inadvertently target the immune system to alter how the body’s immune system perceives its own tissues, making them look foreign. The immune system then attacks the foreign nature of the tissues as if they were incompatible transplants.

“A whole class of drug allergy is likely to be explained by this discovery,” said Professor James McCluskey who led the study with Professor Tony Purcell from the University of Melbourne’s Bio21 Institute and Professor Jamie Rossjohn from Monash University.
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Australian Doctors to Study What Happens During Anaphylaxis
(Tamara Hunter
The West Australian; May 21, 2012)
Simon Brown, an emergency physician at Royal Perth Hospital and researcher with the WA Institute of Medical Research, has begun years of painstaking research to find out what is happening in the cells during an anaphylactic reaction. He wants to know why even a tiny exposure to an allergen can cause a rapid, body-wide response in some people, and little or no reaction in others.

“What we’re trying to do is work out why in some people does the gun go off,” Professor Brown says. “What is it that links the trigger, the antibody, to that generalised response, with the gunpowder going off? There are people with huge levels of allergic antibodies, yet when they get stung all they get is a local reaction – they don’t get a systemic reaction. Some people with very large amounts of antibody and who are clearly allergic just don’t have a reaction, whereas others do.”

Pinpointing the process requires samples taken from people in the midst of anaphylaxis. That means capturing them as they arrive at the RPH emergency department.
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Loss Of Biodiversity May Lead To Increase In Allergies And Asthma
From Medical News Today
Declining biodiversity may be contributing to the rise of asthma, allergies, and other chronic inflammatory diseases among people living in cities worldwide, a Finnish study suggests. Ilkka Hanski et al. from the Department of Biosciences, University of Helsinki, investigated whether reduced human contact with nature and biodiversity influences the composition of commensal skin bacteria and allergen sensitivity in a random sample of 118 teenagers living in eastern Finland. The authors found that subjects living on farms or near forests had more diverse bacteria on their skin and lower allergen sensitivity than individuals living in areas with less environmental biodiversity, such as urban areas or near bodies of water.

The findings suggest that the increasing prevalence of inflammatory diseases may be associated with the changing biodiversity of the environment and commensal skin bacteria.
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Vaccination for Asthma Via Intramuscular Injection
From Science Daily

Research scientists at Inserm and CNRS ( Institut du thorax, CNRS/Inserm/University of Nantes) are working on an innovative vaccine against dust mite allergens. Vaccine was directly injected into the muscle of an asthmatic mouse, a nanovector significantly reduced both the hypersensitivity to the allergen and the associated inflammatory response.

The researchers associated useful genetic sequences of the allergen Derf1 with a nanovector consisting of a synthetic polymer. This DNA sequence, transported by a sort of “molecular taxi” into the muscle cells that ensure protein synthesis of the allergen, modulated the allergic response in asthmatic animals.

Two injections were administered at 3 weekly intervals. They significantly reduced the hypersensitivity of the airways and the levels of inflammatory cytokines, that were found in the lungs of asthmatic mice that had not been vaccinated.
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Tannins show promise for allergen-free peanut products The use of tannic acid could help to reduce the allergic potential of products that contain peanut proteins, say researchers.  Tannins could bind with the proteins to form complexes that will allow them to pass through the digestive tract without no reactivity with IgE.
Si-Yin Chung, Shawndrika Reed
United States Department of Agriculture, Agricultural Research Service, Southern Regional Research Center, 1100 Robert E. Lee Blvd, New Orleans, LA 70124

Nonrespiratory Symptoms Precede Loss of Asthma Control
Research presented at the AAAAI meeting in Orlando showed that parents were able to identify patterns of nonrespiratory symptoms in their children that preceded loss of asthma control. The findings suggest that parents could recognize these early patterns and potentially intervene before an asthma attack. Guidelines do not provide specific information about what signs and symptoms might present before lower respiratory tract symptoms appear, said Dr. Lisanne Newton of the Cleveland Clinic.

Caregivers of children aged 2-11 years with persistent asthma completed daily diaries for 16 weeks, in which they categorized each of 41 signs and symptoms as usual, less than usual, or more than usual. The signs and symptoms were derived from a prior study in which caregivers had identified them as potential early warnings (J. Pediatr. 2009;154:877-81).
Overall there was a significant change from baseline in all symptom types during an episode, compared with a controlled period, which was defined as the days excluding the episodes and the 5 days prior and 2 days after an episode. Specific nonrespiratory signs and symptoms included irritability, low activity levels, tiredness, and sunken eyes. Parents reported an unusual amount of irritability in their children starting 5 days before an episode, with odds ratios of 2.2 at 5 days ahead and 4.1 at 1 day ahead. Unusually low activity levels were significant starting at 3 days before an episode, with odds ratios of 2.7 at 3 days and 4.4 at 1 day prior to the episode. Tiredness was also significantly more common, with an odds ratio of 2.8 at 3 days and 7.6 at 1 day. Sunken eyes were reported starting at 2 days prior, with an odds ratio of 2.5. All of these signs and symptoms were even more common during an episode. Further investigation is needed to determine whether parents would treat their children when these symptoms occurred, and if treatment modification could prevent loss of asthma control and exacerbations.
From reporting by Miriam E. Tucker, Family Practice News Digital Network

How Colds Cause Coughs and Wheezes
ScienceDaily (Mar. 27, 2012) — Cold-like infections make ‘cough receptors’ in the airways more sensitive, making asthmatics more prone to bouts of coughing and wheezing, reveal scientists presenting their findings at the Society for General Microbiology’s Spring Conference in Dublin. The work could lead to drugs that reduce virus-induced coughing in those suffering chronic lung diseases. Researchers at Queen’s University Belfast are investigating ‘cough receptors’ that line the cells of the airway and how these are affected by rhinovirus — a virus frequently responsible for the common cold. The team showed that rhinovirus infection caused an increase in the number of these cough receptors- making the airways more sensitive. Dr Hani’ah Abdullah, who is working on the project, explained how these receptors, called transient receptor potential (TRP) receptors, work. “TRP receptors respond to chemical and physical stimuli in the environment such as pollutants in the air, a change in air temperature and some of the toxic chemicals found in cigarette smoke. Once activated, these receptors cause the individual to cough and wheeze.” she said.
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Intralymphatic Immunotherapy—Coming Alternative to Allergy Shots?

Swiss researchers are investigating a way of short-cutting extended courses of immunotherapy by injecting allergens into the lymph nodes. “Allergen specific immunotherapy (SIT) is the only treatment of IgE mediated allergies that is causative and has a long-term effect. Classically, SIT requires numerous subcutaneous injections of the allergen during 3-5 years. Over the last decade sublingual allergen applications have established as an alternative, but treatment duration could not be shortened. This review focuses on direct administration of vaccines in general and of allergens in particular into lymph nodes with the aim to enhance immunotherapy. Several studies have found that direct injection of antigens into lymph nodes enhanced immune responses. Recently we have focused on intralymphatic allergen administration in order to enhance SIT. Data in mouse models and in clinical trials showed that intralymphatic allergen administration strongly enhanced SIT, so that the number of allergen injections could be reduced to three, and the allergen dose could be reduced 10-100 fold. Intralymphatic injections proved easy, practically painless and safe. In mice and men, intralymphatic immunotherapy injecting allergens into a subcutaneous lymph node markedly enhances the protective immune response, so that both the dose and number of allergen injections can be reduced, making SIT safer and faster, which enhances patient convenience and compliance.”

Senti G, Johansen P, Kündig TM.
Curr Top Microbiol Immunol. 2011;352:71-84.

Animal-Free New Method For Testing Allergenic Substances

(From Medical News Today)
Contact allergy affects around 20% of the population in the western world. Scientists are working intensively to develop alternative test methods that do not require animal testing. A research group at the University of Gothenburg, Sweden, has now developed a unique test method that enables graded results to be obtained using cultured skin cells.

“We have made several discoveries about the mechanism behind contact allergy, one of which is that allergenic substances react with keratin 5 and 14 in the skin. The skin cells form what are known as “blebs” when exposed to allergenic substances, and this can be used to test whether a substance is allergenic”, says Sofia Andersson from the Department of Chemistry at the University of Gothenburg.

Metals such as nickel, and substances in perfume and preservatives are among the most common allergenic substances. They are often components of products that are in contact with the skin, such as jewelry, skin lotions and make up. Contact allergy cannot be cured, and an affected person must avoid the allergenic substance, in order to avoid troublesome eczema.

The EU has now forbidden the testing of cosmetics and their ingredients on animals. It is, however, not a simple matter to fully replace animal tests. Until now, animal-free tests have only been able to determine whether a substance is allergenic or not – such tests have not been able to determine the extent to which a substance causes allergy. Thus, much work remains to be done in developing alternative methods.

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The Immune System Has Protective Memory Cells, Researchers Discover
ScienceDaily (Nov. 28, 2011) — The immune system possesses a type of cell that can be activated by tissues within the body to remind the immune system not to attack our own molecules, cells and organs, UCSF researchers have discovered.

The discovery is likely to lead to new strategies for fighting a range of autoimmune diseases — in which the immune system attacks and harms specific molecules and cells within us — as well as for preventing transplant rejection, according to UCSF researchers who report their findings in the November 27 online edition of the journal Nature.

UCSF immunologist and chair of the Department of Pathology Abul Abbas, MBBS; Michael Rosenblum, MD, PhD, an assistant professor with the UCSF Department of Dermatology; and UCSF postdoctoral fellow Iris Gratz, PhD, used a mouse model of autoimmune disease to discover a role in immune system memory for cells called activated T regulatory cells.
They found that over time a tissue within the body — in this case, skin — defends itself from autoimmune attack by protectively activating a small fraction of T regulatory cells.

“It’s a novel concept — that tissues remember,” Abbas said. “Subsequent exposure to the same protein that elicited autoimmunity in that tissue may lead to less severe inflammatory disease.”

Autoimmune diseases, ranging from minor to severe, affect an estimated 50 million Americans. Immunologists had for decades blamed these diseases on faulty functioning of immune cells known as lymphocytes, including the cells that make antibodies that normally target foreign proteins found on infectious disease pathogens.

In autoimmune disease, lymphocytes may be directed against “self” proteins. In multiple sclerosis, for example, lymphocytes make antibodies that attack proteins in the insulating sheath that surrounds nerves. In lupus, antibodies attack DNA.

But in many cases autoimmune disease may involve abnormal responses by T regulatory cells, the UCSF researchers said. In recent years immunologists have come to recognize the important role that T regulatory cells normally play not only in ramping down an immune response during recovery from infection, but also inpreventing autoimmune responses.

“Instead of an immune response that attacks, it’s an immune response that suppresses attack,” Rosenblum said. The two types of cells exist in a balance, and the balance is disrupted in autoimmune disease.

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Peanut Allergy Breakthrough Inspired by Beer? Two Northwestern Professors Have “Eureka” Moment at Happy Hour

As reported in the Chicago Tribune by William Mullen, Stephen Miller, PhD who studies autoimmune diseases at Northwestern University’s Feinberg School of Medicine and Paul Bryce, PhD who studies food allergies were inspired at a local bar to attempt to find a treatment for peanut allergies using a method that had previously been studied for multiple sclerosis. With MS, the body’s defenses turn on its own tissues as if they were a threat, much as they do with allergens in allergic disease.

For the MS study, Miller hit on the idea of taking blood from a mouse with MS symptoms, attaching myelin protein to certain white blood cells and infusing the blood back into the mouse’s bloodstream.

“The idea is to convince the patient’s immune system that the myelin is not dangerous and to turn off its attack,” Miller said.

The technique, called antigen-specific tolerance therapy, was so successful in stopping the progression of MS in the mice that it is now being tested on humans at the University of Hamburg in Germany.

In their experiments, Bryce and Miller drew blood from specially bred peanut allergic mice and attached peanut protein to white blood cells. They then infused the blood back into the mice and fed them peanut extracts that normally would set off severe allergic reactions.

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Team at Mt. Sinai Finds Two Chinese Herbs Suppress IgE Production in Peanut Allergic Mice Extracts of Rubia cordifolia and Dianthus superbus inhibited the IgE production in vivo and in vitro as well as reduced anaphylactic reactions in peanut-allergic mice, suggesting potentials for allergy treatments. One of the authors of the study, Dr. Xiu-Min Li wrote a guest editorial for us last year. You can read it here.

Win One for the Gipper: Scientists at Notre Dame Inhibit Allergic Reactions Without Side Effects

ScienceDaily (Oct. 13, 2011) — Researchers from the University of Notre Dame have announced a breakthrough approach to allergy treatment that inhibits food allergies, drug allergies, and asthmatic reactions without suppressing a sufferer’s entire immunological system. The therapy centers on a special molecule the researchers designed, a heterobivalent ligand (HBL), which when introduced into a person’s bloodstream can, in essence, out-compete allergens like egg or peanut proteins in their race to attach to mast cells, a type of white blood cell that is the source of type-I hypersensitivity (that is, allergy).

“Unlike most current treatments, this approach prevents allergic reactions from occurring in the first place” says Basar Bilgicer, assistant professor of Chemical and Biomolecular Engineering and Chemistry and Biochemistry and principal investigator in Notre Dame’s Advanced Diagnostics & Therapeutics initiative. While many medicines treat allergies by weakening a person’s entire immune system, this approach only disrupts the process whereby white blood cells bond with allergens in the first place. “It also does not leave patients open to an increased risk for infections or the development of cancers,” explains Bilgicer. “HBLs may be most useful in situations where it’s not possible to speak to or gauge someone’s sensitivity.”

Researchers “Trick” Immune System Into Not Reacting to Peanuts
Researchers at Northwestern’s Feinberg School of Medicine have turned off a life-threatening allergic response by tricking the immune system into thinking peanut proteins aren’t a threat to the body, according to a new preclinical study, reported in Science Daily. They attached peanut proteins onto blood cells of mice and reintroduced them back into their bodies.

“We think we’ve found a way to safely and rapidly turn off the allergic response to food allergies,” said Paul Bryce, an assistant professor of medicine in the division of allergy-immunology at Northwestern University Feinberg School of Medicine. Bryce and Stephen Miller, professor of microbiology-immunology at Feinberg, are co-senior authors of a paper published in the Journal of Immunology. This method has previously been used in autoimmune diseases.

The approach creates a more normal, balanced immune system by increasing the number of regulatory T cells, immune cells important for recognizing the peanut proteins as normal.
“T cells come in different ‘flavors’,” Bryce said. “This method turns off the dangerous Th2 T cell that causes the allergy and expands the good, calming regulatory T cells. We are supposed to be able to eat peanuts. We’ve restored this tolerance to the immune system.” The Northwestern team used a model they developed several years ago to mimic a life-threatening peanut allergy (which the Northwestern team developed several years ago), researchers attached peanut proteins onto white blood cells called leukocytes and infused those back into the mice. After two treatments, the mice were fed a peanut extract. “Their immune system saw the peanut protein as perfectly normal because it was already presented on the white blood cells,” Bryce said. “Without the treatment, these animals would have gone into anaphylactic shock.” Bryce thinks more than one protein can be attached to the surface of the cell and, thus, target multiple food allergies at one time.
The research was funded by the National Institutes of Health and the Food Allergy Initiative.

Air Pollution Can Alter DNA, Make Asthma More Likely for Next Generation
Research from Stanford University indicates that dirty air doesn’t just pollute our lungs, but has long-lasting effects on our DNA by reducing the immune system’s T cells –or—T Regs in the body.

“If you have lower amounts of the cell or the cell doesn’t function or the function is impaired in any way we think that it leads to a higher rate of asthma and a more severe state of asthma,” according to Kari Nadeau M.D., Ph.D., Assistant professor of pediatrics at Stanford University School of Medicine. T Regs help block autoimmune disorders like lupus, type 1 diabetes, and celiac disease. Altering these cells –could mean altering your entire immune system. “When mothers were exposed to it, it caused changes in the DNA of the children born to those mothers,” Dr. Nadeau said.

This would seem to agree with a Danish study of over 45,000 seven-year old children and their mothers. Exposure to particulate pollution in the mother’s workplace during pregnancy was associated with higher rates of asthma. As reported by Reuters, “After adjusting for age, body mass index, allergy and hypersensitivities, smoking, medication and pets, there was a slightly higher risk — about 11 percent — for asthma in children when their pregnant mothers were exposed to particles of both low molecular weight and high molecular weight.”

Deficiency, Airway Remodeling in Severe Asthma Cases

London researchers discovered that lower vitamin D levels could be associated with poorer lung function in children severe therapy-resistant asthma (STRA).

Findings revealed that lower levels of vitamin D might cause structural changes in the airway muscles, making breathing harder. Approximately 5 to 10% of asthmatic children do not respond to standard treatment of inhaled corticosteroids (ICS), resulting in more asthma episodes and asthma-related illnesses, requiring more healthcare services.

Atul Gupta, MRCPCH, M.D., a researcher from Royal Brompton Hospital and the National Heart and Lung Institute (NHLI) at Imperial College and King’s College London explained:

“This study clearly demonstrates that low levels of vitamin D are associated with poorer lung function, increased use of medication, worse symptoms and an increase in the mass of airway smooth muscle in children with STRA. It is therefore plausible that the link between airway smooth muscle mass and lung function in severe asthma may be partly explained by low levels of vitamin D.”

They measured the relationships between vitamin D levels and lung function, medication usage and symptom exacerbations and examined tissue samples from children’s airways in the STRA group to assess structural changes in the airway’s smooth muscle.

Published online ahead of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine’s print edition

Genomic Research Points to Individualized Asthma Treatment

Asthma is now considered a “syndrome” not a disease. That is, it is a set of symptoms that have many different causes and triggers—some allergic, some non-allergic, some viral and so on. This accounts in part for the different ways people respond to treatment. The most effective treatment is daily doses of inhaled corticosteroids (ICS) to reduce airway inflammation, which is present in all asthma no matter what the cause. But approximately a third of asthmatics do not respond to ICS, and doctors have long wondered why.

Now we may have the beginning of an answer. Genetics.

In a study published in the New England Journal of Medicine, scientists found that patients with a particular gene variant had lower levels of forced expiratory volume after treatment with ICS—that is their lungs weren’t as strong as others without this genetic variant. While “personal” treatment is years away, this research points the way to being able to tailor it to individuals based on studies of their DNA.

Australian Researchers Discover Gene Variations That May Account for Asthma Risk, Other Allergic Disease

An international team of researchers led by Manuel Ferreira from the Queensland Institute of Medical Research in Brisbane, Australia have recently conducted a study to find new genetic variations that are responsible for increasing the risk of asthma.
The team compared the genomes of thousands of asthma patients with a diverse group of non-asthmatics. They found two new genetic variants that posed strong asthma risks; rs4129267 in the interleukin-6 receptor (IL6R) and rs7130588 on chromosome 11q13.5.

Interleukin 6 (IL-6) is a cytokine that plays an important role in immunity and inflammation; the new discoveries suggest that drugs that block these particular types of receptors should be considered for clinical trials to prevent or reduce asthmatic inflammation. The other variant rs7130588, on chromosome 11q13.5, was found to be more common in allergic asthma patients, suggesting there is a gene in this chromosome region that plays a role in the development of allergic sensitization.

According to the authors, “At this stage it is unclear which gene underlies the association with 11q13.5. Given that no specific gene in this region has been directly implicated in allergic disease previously, further characterization of this region of association is likely to discover novel molecular mechanisms involved in the causality of eczema, atopy, and asthma.”
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New Asthma Risk Gene Emerges from Study of Diverse Populations
By Jeffrey Norris, University of California, San Francisco website on August 16, 2011
“Asthma rates in the United States are higher among African Americans and Latinos in comparison to European Americans, but the causes of asthma in all populations still are only poorly understood. Researchers now have discovered a genetic variation associated with increased asthma risk in people of African ancestry — the result of a new DNA analysis spanning the entire genomes of thousands of asthma sufferers. The scientists also have confirmed an asthma association for four other common gene variations that came to light late last year in a large study of Europeans. The new study demonstrates that these genes appear to affect risk in other populations, as well.

“The research collaborators discovered that a genetic variation in a gene called PYHIN1 was associated with about a 34 percent higher risk of asthma in African Americans and African Caribbeans. The variation is common in these groups — close to 30 percent of those with African ancestry inherited this variant. However the variation was not found in populations of European ancestry, and was present in only a few Latinos in the study.

“The consortium researchers determined that four other markers of common genetic variations that last year were found to be associated with increased asthma risk in a large European study also are associated with asthma risk in the other ethnic groups. The large size of these studies was a key to identifying these genes, the researchers say.
“Additional research will be required to pinpoint the specific DNA and biological mechanisms responsible for the associations discovered in the study.

“The consortium of scientists who reported the findings online on July 31 in advance of print publication in Nature Genetics hail from nine independent research groups. They pooled and compared data from their own separate study populations to empower their statistical analysis.”
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Use of allergen components begins a new era in pediatric allergology

Magnus P. Borres, Motohiro Ebisawa, Philippe A. Eigenmann
Pediatric Allergy and Immunology Volume 22, Issue 5, pages 454–461, August 2011

Abstract

“Molecular allergology is a breakthrough science that enables the quantification of IgE and IgG antibodies against individual allergen protein components at a molecular level.

“The diagnosis of IgE-mediated allergic disorder among children is based on clinical history and sensitization demonstrated through an allergy test. Identifying whether the sensitization is primary (species specific) or a result of cross-reactivity to proteins with similar protein structures helps the clinician to judge the risk of allergic reaction. This is possible today because allergen component tests are now available for clinicians to use in everyday practice.”

“The measurement of allergen components has the potential to reduce the number of food challenges. The reason why food challenge not yet can be replaced is that not all allergic sources in the various foods have yet been completely characterized and evaluated. From a health economic perspective, the health service would save money and reduce the risks if allergen components were used instead of food challenges. We therefore need a method even safer and better than the challenges we use today. The double-blind placebo-controlled food challenge (DBPCFC) has long been the standard in the diagnosis of food allergy as a benchmark test from which to judge the diagnostic characteristics of the clinical history, skin prick test, and IgE antibody serology….

“The use of allergen components will pave the way for a more individual approach when we investigate and care for our patients with suspected allergic diseases. Using molecular allergology, we can now already better diagnose, prognose, and grade the allergic diseases. We can also get help with choosing a more individualized treatment and get better support regarding which individuals should be advised to avoid
specific allergens.”
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Pitt Team Finds Molecular Pathway That Leads To Inflammation In Asthma

Researchers at the University of Pittsburgh School of Medicine have identified a molecular pathway that helps explain how an enzyme elevated in asthma patients can lead to increased mucus production and inflammation that is characteristic of the lung condition. Their findings, reported online in this week’s Proceedings of the National Academy of Sciences, reveal unique interactions between biological molecules that could be targeted to develop new asthma treatments.

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Scientific American has a good round-up of news on various peanut-allergy research now underway. It contains a description of the “unconventional” work being done at Mt. Sinai by our contributor, Dr. Xiu-Min Li, using Chinese herbal compounds, which are undergoing clinical trial. If you wish to participate, read what Kathy Franklin said on this site.

Nanoparticles Offer Hope for Common Skin Allergy
ScienceDaily (Apr. 3, 2011) — Tiny particles only billionths of a meter in diameter — about two thousand would fit across the width of a human hair — could offer big hope in a small package to the many millions of people who are allergic to the nickel in everything from jewelry to coins and cell phones, say scientists at Brigham and Women’s Hospital (BWH).

In the April 3 online issue of Nature Nanotechnology, the team will report a new approach to preventing the common skin allergy. Approximately ten to fifteen percent of the US population, or over 30 to 45 million people, plus many more worldwide, are allergic to the nickel found in many everyday objects. For these people the metal causes a red, itchy rash when it comes into contact with their skin.

The new approach would put nanoparticles with calcium into skin cream, which would prevent absorption.

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Listen to Kathleen Barnes, PhD, of Johns Hopkins talk about the Hygiene Hypothesis and its relation to our understanding of allergic diseases here.

Vaccine to Cure Asthma Brought on by House Dust Mite Allergies?

Monash University (Australia) researchers are working on a vaccine that could completely cure asthma brought on by house dust mite allergies. Professor El Meeusen, who is working with Professor Robyn O’Hehir, both from the Faculty of Medicine, Nursing and Health Services, believes that a vaccine for people with house dust mite allergies will have a range of health and financial benefits for patients and the government.
“We are aiming to develop a vaccine that can be completely delivered in two to three doses. That means a person suffering from a house dust mite allergy will be able to breathe easily from their final dose,” Professor Meeusen said.
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Xolair May Help Speed Up Immunotherapy for Milk Allergy

According to data presented at the AAAAI meeting in San Francisco, “’Rush’ desensitization for food allergies may be feasible by toning down immune response with the monoclonal antibody omalizumab (Xolair), according to a proof-of-concept study.

“After nine weeks of omalizumab pretreatment, most milk-allergic children were able to go through the entire first phase of oral immunotherapy desensitization to receive a dose of 2,000 mg of powdered milk in just one day, Kari C. Nadeau, MD, of Stanford University in Palo Alto, Calif., and colleagues found.

“This process typically takes 16 to 24 weeks without omalizumab, Nadeau told attendees.”
Crystal Phend, Senior Staff Writer, MedPage Today—Read more here

Integrative Medicine Offers New Hope for Asthmatics
(Taken from an article in the Sacramento Bee by Drs. Kay Judge and Maxine Barish-Wreden Published: Sunday, Feb. 20, 2011)
Those looking for alternatives to current guideline asthma therapy will be encouraged by a recent article in the journal Alternative Therapies, which looked at the cost and benefits of an integrative medicine approach to treating asthma as part of a study conducted at the Continuum Center for Health and Healing, an integrative medicine center at Beth Israel Medical Center in New York.
154 people with mild to severe asthma were randomized into two groups. The first continued on its usual prescription meds for asthma. The second took its usual asthma meds and those in the group were also trained to incorporate the following integrative medicine practices into their daily routines:
• Attend two nutrition classes where they learned about foods that can trigger asthma and inflammation. They then engaged in an elimination diet for two to four weeks to identify their own particular dietary triggers, and eliminated those foods from their diet.
• Took daily fish oil capsules containing 860 mg of EPA and 580 mg of DHA.
• Took 1,000 mg of vitamin C daily.
• Took a standardized extract of hops, an anti- inflammatory herb.
• Attended two yoga classes and also learned how to practice the healing breath work of yoga known as pranayama; they were encouraged to do this on a daily basis.
• Attended an expressive journaling session where they wrote about the most traumatic stressful event of their lives. (Expressive writing like this has been shown in some studies to decrease symptoms of asthma.)
After six months, people in the treatment group were found to have significant improvements in quality-of-life measurements compared with the control group, and their overall physical and mental health were also improved, with no significant side effects.
Pulmonary function tests, however, did not show significant changes in either group over time. The researchers did not measure any changes in the use of prescription asthma medications between the two groups.
The authors concluded that this “low-cost, low-risk lifestyle intervention can significantly improve both disease-specific and overall quality of life in adults with asthma over a six-month period.”

(Note: for a different approach to integrative medicine, read our piece by Dr. Xiu-Min Li here.)

Enzyme “Master Switch” could be key to new asthma treatment

Researchers have proved that a single “master switch” enzyme, known as aldose reductase, is key in producing excess mucous that clogs the airways of people with asthma and chronic obstructive pulmonary disease (COPD). The enzyme’s action can be blocked by drugs whose safety has been shown in clinical trials for other diseases – a discovery that could improve therapies for the 510 million people worldwide suffering from asthma and COPD.
The findings are from a University of Texas Medical Branch at Galveston study published in the online journal PLoS One.
Using cell culture and laboratory mouse experiments, the researchers showed that the enzyme, aldose reductase, is essential to a process known as goblet cell metaplasia that is seen in both asthma and COPD. In goblet cell metaplasia, exposure to allergens such as pollen, mold and dust mites initiates a series of biochemical reactions that causes the cells that line the air passages of the lungs to change from their normal state into so-called “goblet cells,” which produce substantial amounts of excess mucus. Healthy individuals’ lungs contain very few goblet cells, but patients who die from asthma — an estimated 5,000 people annually — have significantly higher numbers of these cells.
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Mold in the Lungs?
Scientists investigating the allergic reactions that asthmatics suffer towards a common mould have discovered that many people with asthma actually had the mould growing in their own lungs.
The research led by University of Leicester scientists at Glenfield Hospital has been published in the December 2010 issue of the American Journal of Respiratory and Critical Care Medicine.
The team based in the Institute for Lung Health at the University of Leicester and Glenfield Hospital examined the impact on asthmatics of a common environmental mould, Aspergillus fumigates, usually found in soil and compost heaps.
Professor Andy Wardlaw from the University of Leicester said: “Asthma is a very common condition where the breathing tubes (bronchi) can go into spasm making it difficult to breathe. Around a fifth of adults with severe asthma, which they have had for a long time, get permanent (fixed) narrowing of their bronchi. It is known that A. fumigatus can grow in the lungs of some people with asthma and mould allergy, which can cause severe lung damage.
“This problem is thought to only affect a very small number of people with asthma; however, about half of people with severe asthma have evidence of allergy to moulds like A. fumigatus.”
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Allergies and Wheezing Illnesses in Childhood May Be Determined in the Womb
ScienceDaily (Oct. 25, 2010) — A child’s chances of developing allergies or wheezing is related to how he or she grew at vital stages in the womb, according to scientists from the University of Southampton.
The new research, funded by the Medical Research Council (MRC) and the British Lung Foundation, and undertaken at Southampton General Hospital, reveals that fetuses which develop quickly in early pregnancy but falter later in pregnancy are likely to go on to develop allergies and asthma as children. Scientists believe this is due to changes in the development of their immune system and lungs.
A fetus that grows too slowly in the womb is also more likely to become an infant who wheezes with common colds, possibly as a result of narrower airways in its lungs.
“Childhood allergies and asthma have become an epidemic in developed countries over the last 50 years. This research shows that in order to combat this, we need to understand more about how babies develop in the womb,” comments Keith Godfrey, Professor of Epidemiology and Human Development at the University of Southampton and Deputy Director of the NIHR Nutrition Biomedical Research Unit at Southampton General Hospital.

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Discovery of Taste Receptors in the Lungs Could Help People With Asthma Breathe Easier

Researchers at the University of Maryland School of Medicine in Baltimore have discovered that bitter taste receptors are not just located in the mouth but also in human lungs, which may have implications for the treatment of asthma and other obstructive lung diseases.
“The detection of functioning taste receptors on smooth muscle of the bronchus in the lungs was so unexpected that we were at first quite skeptical ourselves,” says the study’s senior author, Stephen B. Liggett, M.D., professor of medicine and physiology at the University of Maryland School of Medicine and director of its Cardiopulmonary Genomics Program.
The team found the taste receptors by accident, during an earlier, unrelated study of human lung muscle receptors that regulate airway contraction and relaxation. The taste receptors in the lungs are the same as those on the tongue.
The researchers exposed bitter-tasting compounds to human and mouse airways, individual airway smooth muscle cells, and to mice with asthma. The findings are published online in Nature Medicine.
Most plant-based poisons are bitter, so the researchers thought the purpose of the lung’s taste receptors was similar to those in the tongue — to warn against poisons.
The researchers tested a few standard bitter substances known to activate these receptors. “It turns out that the bitter compounds worked the opposite way from what we thought,” says Dr. Liggett. “They all opened the airway more profoundly than any known drug that we have for treatment of asthma or chronic obstructive pulmonary disease (COPD).” Dr. Liggett says this observation could have implications for new therapies. “New drugs to treat asthma, emphysema or chronic bronchitis are needed,” he says. “This could replace or enhance what is now in use, and represents a completely new approach.”
“The work of this team exemplifies what it takes to make real improvements in treating certain diseases,” says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and dean of the University of Maryland School of Medicine. “These researchers were willing to take chances and ask questions about an unlikely concept. Why are taste receptors in the lungs? What do they do? Can we take advantage of them to devise a new therapy? In the end, their discoveries are in the best tradition of scientific research.”

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On the Horizon…

So That’s Why We’re Allergic to Sun Creams
ScienceDaily (Oct. 10, 2010) — What happens to sunscreens when they are exposed to sunlight? And how is the skin affected by the degradation products that form? This has been the subject of research at the University of Gothenburg and Chalmers University of Technology that will be presented at the upcoming dermatologist conference in Gothenburg.
“We know that sun creams pass through the skin into our bodies, but we don’t know what effects they have on us,” says Isabella Karlsson, doctoral student at the Department of Chemistry at the University of Gothenburg’s Faculty of Science. “Many of them actually break down in the presence of sunlight. We therefore wanted to look at what can happen to the chemical sun protection agents when exposed to UV rays, and how the degradation products that form affect the skin.”
In their study, the researchers have come up with an explanation of what happens during this process. “Arylglyoxales, one of the degradation products, turned out to be highly allergenic,” says Karlsson. “Which could explain why some people are allergic to creams that contain dibenzoylmethanes, one of the UVA-absorbing substances in sun creams.”
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Safety, tolerability, and immunologic effects of a food allergy herbal formula in food allergic individuals

Julie Wang, MD, Sangita P. Patil, PhD, Nan Yang, PhD, Jimmy Ko, MD, Joohee Lee, MD, Sally Noone, RN, Hugh A. Sampson, MD, Xiu-Min Li, MD

Food allergy is a common and serious health problem. A new herbal product, called food allergy herbal formula 2 (FAHF-2), has been demonstrated to have a high safety profile and potent long-term efficacy in a murine model of peanut-induced anaphylaxis.
Objective
To evaluate the safety and tolerability of FAHF-2 in patients with food allergy.
Methods
In this randomized, double-blinded, placebo-controlled, dose escalation, phase 1 trial, patients received 1 of 3 doses of FAHF-2 or placebo: 2.2 g (4 tablets), 3.3 g (6 tablets), or 6.6 g (12 tablets) 3 times a day for 7 days. Four active and 2 placebo patients were treated at each dose level. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data were monitored. Immunomodulatory studies were also performed.
Results
Nineteen food allergic participants were included in the study. Two patients (1 in the FAHF-2 group and 1 in the placebo group) reported mild gastrointestinal symptoms. One patient withdrew from the study because of an allergic reaction that was unlikely related to the study medication. No significant differences were found in vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data obtained before and after treatment visits. Significantly decreased interleukin (IL) 5 levels were found in the active treatment group after 7 days. In vitro studies of peripheral blood mononuclear cells cultured with FAHF-2 also demonstrated a significant decrease in IL-5 and an increase in culture supernatant interferon ? and IL-10 levels.
Conclusions
FAHF-2 appeared to be safe and well tolerated in patients with food allergy.

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(Note: a phase one study is a long way from a marketable drug. It proves that the medication is not inherently dangerous. For more on this research, see chapter 10 Asthma Allergies Children: a parent’s guide.)

Cure for Peanut Allergy Within 3 Years?
Dr Andrew Clark, a researcher at Addenbrooke’s hospital in Cambridge, is leading a £1million National Health Service [NHS] sponsored research project to find a “cure” for peanut and other food allergies. It could also be the beginning of the end for all food allergies, he claimed.

The new study builds on a successful immunotherapy trial in which 23 children were given tiny doses of peanut flour every day, gradually increasing the dose until now they can eat five or more nuts a day.
Earlier immunotherapy trials for peanut allergies were unsuccessful and caused serious reactions. The key difference is that the Cambridge team put small doses of flour into yoghurt, rather than injecting peanut extract or oil.

The news was presented at the annual meeting of the American Association for the Advancement of Science.
The new study has recruited 104 children for a three year trial. (more…)

Food Allergy-Related Disorder Linked to Master Allergy Gene
Scientists have identified a region of a human chromosome associated
with eosinophilic esophagitis (EoE), a recently recognized allergic disease.
People with EoE frequently have difficulty eating or may be allergic to one or more foods. This study suggests that a suspected so-called master
allergy gene may play a role in the development of this disorder.

EoE is characterized by inflammation and accumulation of a specific type of
immune cell, called an eosinophil, in the esophagus. Symptoms vary with age: In young children a major symptom is spitting up food, while in older children and adults, the condition may cause food to become stuck in the esophagus. These symptoms may improve when a person with EoE is restricted to a liquid formula diet that contains no protein allergens or is placed on a diet that lacks six highly allergenic foods (milk, soy, eggs, wheat, peanut and seafood). EoE is not the same as more common food allergies. Little is known about what causes EoE, but the disease runs in families suggesting that specific genes may be involved. (more…)