Tag: allergies

A Link Between Mental Health and Allergies

Photo by Andrea Piacquadio on Unsplash

Researchers have reported finding a link between allergic diseases and mental health conditions, but one which was likely not causal.

The analysis of data from the UK Biobank was published in Clinical and Experimental Allergy. The researchers used a genetic instrument derived from associated variants for a broad allergic disease phenotype to test for causal relationships with various mental health outcomes. They also investigated whether these relationships were specific to atopic dermatitis (AD), asthma or hayfever.

The researchers found that people with asthma, atopic dermatitis, and hay fever also had a higher likelihood of having depression, anxiety, bipolar disorder, or neuroticism. However neither category appeared to play a role in causing the other. Nevertheless, future studies should investigate whether interventions that aim to improve allergic diseases might also have an effect on mental health (and vice versa).

“Our research does not rule out a potential causal effect upon the progression of disease, which is yet to be investigated and could help uncover novel treatment strategies for allergic disease or mental health traits,” said lead author Ashley Budu-Aggrey, PhD, of the University of Bristol.

Senior author Hannah Sallis, MSc, PhD, added that the research used a combination of approaches and data from several studies. “This helps to strengthen our confidence in the findings,” she said. “Establishing whether allergic disease causes mental health problems, or vice versa, is important to ensure that resources and treatment strategies are targeted appropriately.”

Source: Wiley

New Allergen Pathway Discovery Could Yield New Meds

Photo by Britanny Colette on Unsplash

Researchers have uncovered the mechanism by which the innate immune system is triggered by allergens, such as insects, mites, and fungi.

In Nature Immunology, researchers revealed new details about how the body’s “type 2 innate immune response” system works, which could yield a new medication for allergy control.

“Disrupting this allergen sensing pathway could provide a unique opportunity to counteract type 2 immunity and alleviate allergic inflammation,” said senior author Marc Rothenberg, MD, PhD, Director, Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center

In addition to Rothenberg, the research team included , Mark Rochman, PhD, Yrina Rochman, PhD, Julie Caldwell, PhD. Lydia Mack, MS, Jennifer Felton, PhD, Jeff Habel, PhD, Aleksey Porollo, PhD and Chandrashekhar Pasare, DVM, PhD.

Multiple allergens had been shown to induce a similar IL-33 response upon breaching the epithelial layer of mucosal membranes, a process which the researchers pinned down.

“This breakthrough was made possible by new insights into the role of ripoptosome signaling and caspases in allergic inflammation,” said Michael Brusilovsky, MMedSc, PhD, who was the first author of the study.

Specifically, the allergens trigger activity among an interlocked set of cell death-inducing signals called the ripoptosome. This signaling “platform” includes numerous components, but for allergic inflammatory reactions, the key player appears to be a molecular switch called caspase 8. The investigators named the pathway, “RipIL-33” as IL-33 is processed (ripped) by the ripoptosome.

How allergens are sensed has remained a mystery.

“The discovery of this surprising mechanism is the most important breakthrough in understanding how the innate immune system senses allergens to initiate a type 2 response and subsequent allergic inflammation,” said Pasare, one of the senior authors of the study.

In mice, inhibiting caspase 8 reduced the IL-33 response to allergens and limited bronchial inflammation in the lungs. Analysis revealed a similar process in humans/ 
“In the human allergic disease eosinophilic esophagitis (EoE), we found that ripoptosome activation markers and mature IL-33 levels dynamically correlated with the degree of esophageal eosinophilia and disease activity,” the study states.

The next steps include studying the RipIL-33 pathway in human allergic reaction and determining whether existing or new drugs could disrupt it.

Source: News-Medical.Net

Common Probiotic Altered to Grow in Dairy Products

A glass of milk. Source: Pixabay via Pexels

Researchers at the University of Helsinki have created a strain of the Lacticaseibacillus rhamnosus GG probiotic that can reproduce in dairy products.

Lacticaseibacillus rhamnosus GG, or LGG, is the most studied probiotic bacterium in the world. However, it cannot utilise lactose found in milk or break down the milk protein casein. This makes the bacterium grow poorly in milk and is the reason why it must be added separately to probiotic dairy products.

While attempts have been made to get L. rhamnosus GG to thrive in milk through genetic engineering, strict restrictions have prevented the use of such modified bacteria in human food.

Thanks to a recent breakthrough made at the University of Helsinki, Finland, with researchers from the National Institute for Biotechnology and Genetic Engineering, Pakistan, features have now been successfully added to the LGG probiotic without gene editing, making it able to grow in milk.

The method instead took advantage of conjugation, a DNA exchange technique used in certain bacterial groups to transfer their traits to other bacteria. A bacterium produces a copy of its plasmid, a ring-shaped piece of DNA, and then transfers it to an adjacent bacterium. The spread of plasmids, which carry traits useful for bacteria, can be rapid among bacterial communities – and can also further the spread of problematic traits such as antibiotic resistance.

A specific Lactococcus lactis bacterial strain grown in the same place provided the lactose and casein-utilising plasmid to the Lacticaseibacillus rhamnosus GG.

“The new LGG strain is not genetically modified, which makes it possible to consume it and any products containing it without any permit procedures,” explained project leader Per Sari, Professor of Microbiology at the University of Helsinki.

The new strain can be used as a starting point in the development of new dairy products where the probiotic concentration increases already in the production stage. In other words, the probiotic need not be separately added to the final product. Furthermore, lactose- and casein-hydrolysing bacteria added to milk could help produce products suitable for people with dairy allergies.

This new LGG strain could also be better suited to growing in the infant gut, where it can utilise the casein and lactose in breastmilk to grow, thereby producing more protective lactic acid than the original strain.

“Lactic acid lowers the pH of the surface of the intestine, reducing the viability of many gram-negative pathogenic bacteria, such as E. coli, Salmonella and Shigella, which threaten the health of infants. Moreover, in larger numbers the new LGG strain can potentially be more effective at protecting infants than the old strain. After all, LGG has previously been shown to alleviate infantile atopic dermatitis and boost the recovery of the gut microbiota after antibiotic therapies.”

The researchers are in discussions about further applications of their research.

Source: News-Medical-Net

Journal information: Hussain, N., et al. (2021) Generation of Lactose- and Protease-Positive Probiotic Lacticaseibacillus rhamnosus GG by Conjugation with Lactococcus lactis NCDO 712. Applied and Environmental Microbiology. doi.org/10.1128/AEM.02957-20.

Rollout of Peanut Allergy Treatment Stalled by Pandemic

Approved in late January 2020, the only FDA-approved peanut immunotherapy was due to be released onto the US market, but the arrival of the pandemic effectively shut it down.

The peanut-powder Palforzia allergen treatment is designed to desensitise peanut allergies in children and adolescents, and circumvent potentially life-threatening reactions.

It is unclear to what extent peanut allergy immunotherapy (IT) and other forms of IT will be embraced by the US public. While subcutaneous IT has been practised for a long time, oral IT such as sublingual IT tablets are relatively new, with only a few products currently having regulatory approval in the US and Europe.

However, there are questions as to whether the US will ever widely accept IT, given factors such as the high treatment burden. Speaking to MedPage Today, Edwin Kim, MD, director of the University of North Carolina Food Allergy Initiative in Chapel Hill, said that it may not be clear for a while to what extent the treatment is accepted.

“COVID-19 shined a spotlight on the downsides of a treatment that requires so many physician visits,” he said. “If it was an easy treatment we might have seen more uptake, but it’s not an easy treatment.”

Thomas Casale, MD, of the University of South Florida in Tampa, acknowledged to MedPage Today that Palforzia’s uptake in the past year has been slow as “A treatment like this requires a lot of contact with the patient.”

The dosing schedule involves around a dozen physician visits, of 30-90 minutes duration each.  A single-day initial dose escalation phase is needed, with up-dosing every two weeks with physician observation to attain 11 increasing dose levels. After this, there is a daily home-dosing maintenance phase.

The 300-mg peanut protein maintenance dose is equivalent to eating a single peanut. “If you are able to tolerate 300 mg of peanut you can effectively prevent about 95% of adverse reactions,” Casale said. “So 300 mg is an important indicator of some degree of safety.”
In pooled trial data on Palforzia presented by Dr Casale, only 1.2% of long-term patients had a treatment-related severe systemic allergic reaction, all of which were treated with epinephrine.

“I think that after COVID is gone, which hopefully will be sooner than later, the uptake of this type of therapy will be a lot greater than it is today,” Dr Casale said.

Viaskin Peanut, an extracutaneous peanut IT, is undergoing investigational trials, with the FDA rejecting application for its approval. The agency cited concerns about the impact of patch-site adhesion on efficacy, and demanded modifications and additional trials.

Christina Ciaccio, MD, chief of allergy/immunology and pediatric pulmonology and sleep medicine at the University of Chicago, said that there were many challenges remaining.

“We have numerous forms of immunotherapy that are currently under investigation,” she said. “The fact that only one allergen-specific IT treatment for food allergy has been approved by the FDA highlights the remaining challenges.”

“For those that do have peanut allergies, this treatment [IT] is not universally effective and it is not universally available,” Ciaccio said. “The side effects are too frequent, and as it stands right now, this is a life-long therapy. These are all things we would like to work on.”

Source: MedPage Today

Smoking Risks for Allergic and Asthmatic Cannabis Users

A survey in the US has shown that cannabis users are often asthmatic, and some have allergies from cannabis smoking or its second-hand smoke.

Cannabis allergies can potentially cause respiratory symptoms, contact urticaria, angioedema, and uncommonly anaphylaxis. Inhalation of cannabis may also manifest in allergic rhinitis, conjunctivitis, wheezing, and throat oedema. Given the widespread legal use of cannabis, more information is needed on the effects of cannabis use, particularly smoking, on individuals with asthma and allergies.

The anonymous survey, conducted in concert with the Allergy & Asthma Network, consisted of 489 participants, 18% of whom reported cannabis use. A surprising 60% were asthmatic, and 40% had uncontrolled asthma. 

Inhalation routes were the most popular way of taking cannabis. About half of users smoked cannabis, while a third vaped it. Only 40% reported being asked by their physician about cannabis use, and about the same proportion of participants were willing to talk to a physician about their cannabis use, said study co-author and cannabis allergy expert, William Silvers, MD.

“In order to more completely manage their allergy/asthma patients, allergists should increase their knowledge about cannabis and inquire about cannabis use including types of cannabinoid, route of use, reasons for use, and adverse effects,” said Dr Silvers. “As with cigarette smoking, efforts should be made to reduce smoking of cannabis, and recommend other potentially safer routes such as edibles and sublingual tinctures.”

Reported positive effects of cannabis use (eg, reduced pain, calm, improved sleep) were more frequent than adverse effects (eg, cough, increased appetite, anxiety). Approximately 20% of survey respondents reported coughing from cannabis, which was associated with smoking cannabis; this was cause for concern as it may indicate smoking risks for cannabis users.

“It surprised me that over half of the cannabis users in this study who have asthma were smoking it,” said principal investigator Joanna Zeiger, PhD. “And further, of those with uncontrolled asthma, half reported smoking cannabis. We also found that people with asthma are not routinely being asked or advised by their physician about cannabis and how they are consuming it.”

The researchers commented that further research into the relationship of cannabis and allergies is warranted.
“We look forward to future studies of larger, more diverse cohorts to better explore more deeply the effect of cannabis use on asthma and other allergic disorders,” said Dr Zeiger.

Source: News-Medical.Net

Journal information: Zeiger, J. S., et al. (2021) Cannabis attitudes and patterns of use among followers of the Allergy & Asthma Network. Annals of Allergy, Asthma & Immunology.doi.org/10.1016/j.anai.2021.01.014.

Black American Children Have Higher Rates of Shellfish and Fish Allergies

A study from Rush University Medical Center in the US has shown that black children in that country are more likely to have allergies to fish and shellfish than white children.

Some 8% of children in the US suffer from food allergies, which can result in signs and symptoms such as hives, breathing and digestive problems or anaphylaxis, sometimes severe enough to be life-threatening.

Lead author Dr Mahboobeh Mahdavinia at Rush University Medical Center, explained: “Food allergy is a common condition in the U.S., and we know from our previous research that there are important differences between African-American and white children with food allergy, but there is so much we need to know to be able to help our patients from minority groups.”

The study found that the black children were more likely to have an allergy to shellfish and fin fish, and also higher odds of having a wheat allergy, compared to the white children. The researchers believe the reason for this is environmental and socioeconomic: in the US, black children are more likely to be exposed to cockroaches than white children due to the increased probability of living in more socioeconomically deprived areas.

Tropomyosin, a protein found in two common household allergens, dust mite and cockroaches, share 80% of amino acid sequencing with shellfish. Some 72-98% of individuals allergic to prawns have an immunoglobin E response to tropomyosin. It has also been found in fin fish. Although the exact mechanism by which the allergy is established is not known, it provides evidence as to the importance of reducing the exposure of black children to cockroaches.

The study also showed that shellfish allergy was associated with increased asthma risk in black children. “This information can help us care for not only a child’s food allergy, but all of their allergic diseases, including asthma, allergic rhinitis and atopic dermatitis,” said co-author Susan Fox, PA-C, MMS, an allergy and immunology physician assistant at Rush University Medical Center.

The increased risk of asthma combined with food allergies can prove a lethal combination for children. “A major concern is that there is a higher prevalence of asthma in African-American children with food allergies when compared with white children with food allergies. Approximately 70% of fatal food anaphylaxis is accompanied by asthma. African-American children are at a two- to threefold risk of fatal anaphylaxis compared to white children,” Dr Mahdavinia said. “By knowing this information, it can identify [our] most at risk patients.

“We need to conduct further research to identify food allergies and food sensitivities among all races and ethnicities so we can develop culturally-sensitive and effective educational programs to improve food allergy outcomes for all children,” Dr Mahdavinia concluded.

Source: News-Medical.Net

Itching in Severe Eczema Uses a Different Pathway

A study shows that there are two molecular pathways for conveying sensations of itching, with the itching of severe eczema following an unexpected route.

In normal eczema, cells in the skin convey the itching sensation, releasing histamines. This can be blocked with antihistamines.

“Years ago, we used to think that itch and pain were carried along the same subway lines in the nerves to the brain, but it turned out they weren’t, and these new findings show there’s another pathway entirely that’s causing these episodes of acute itching in eczema patients,” said principal investigator Brian S Kim, MD, Washington University School of Medicine. “The itch can be maddening. Patients may rate their chronic itch at around a 5 on a scale of 10, but that goes up to 10 during acute itch flares. Now that we know those acute flares are being transmitted in an entirely different way, we can target that pathway, and maybe we can help those patients.”

With severe itching in eczema, different cells in the blood are activated, transmitting great quantities of non-histamine molecules which also convey the itching sensation. This renders antihistamines usesles in trying to control the itch. The discovery of this new pathway offers new possibilities for treating other conditions as well. Recent studies have tried to block Immunoglobulin E (IgE) in response to allergies.

“We’ve connected acute itching in eczema to allergic reactions transmitted by an entirely different population of cells,” explained Kim. “In patients who experience episodes of acute itching, their bodies react in the same way as in people with acute allergy. If we can block this pathway with drugs, it might represent a strategy for treating not only itch but other problems, including perhaps hay fever and asthma.”

The team found that when mice with eczema made IgE in response to environmental allergens, they began to itch. However, instead of activating mast cells which produced histamine, the IgE activated basophils (a kind of white blood cell), activating a different nerve pathway to normal itching.

The discovery that eczema is exacerbated by allergens may help people avoid severe itching episodes, as well has helping the development of new targets for treatment.

Source: News-Medical.Net

Journal information: Wang, F., et al, A basophil-neuronal axis promotes itch. Cell, 2021 doi.org/10.1016/j.cell.2020.12.033.

Stomach Bugs Induce Irritable Bowel Syndrome

Researchers have pinpointed a localised biological mechanism behind irritable bowel syndrome (IBS), a chronic gastrointestinal condition where eating certain foods causes subsequent abdominal pain or discomfort.

Around 20% of people experience IBS, and diets such as gluten-free ones provide some relief. However, the exact cause was unknown, as the patients did not have allergic responses nor did they have coeliac disease, causing many physicians to dismiss it as psychological.A healthy immune system tolerates foods, and the first link is understanding how the tolerance is removed. Previous work showed that there was a link between mast cells and food, and that blocking histamine in people with IBS relieved the symptoms.

People with IBS often report their symptoms begin following a gastrointestinal infection, so the researchers reasoned that an infection associated with a particular type of food in the guy might sensitise the immune system to that food.The team fed mice with ovalbumin (an egg protein) and then infected them with a stomach bug. The mice were then fed ovalbumin again, and the researchers recorded elevated mast cell activation, histamine levels and digestive intolerance. In control mice who were fed with ovalbumin but who were not infected with the stomach bug, there was no response.

Breaking down the chain of events leading to the sensitisation, the researchers discovered that there was a localised immune response in the part of the guy infected by the bacteria, but did not produce the more generalised symptoms of a food allergy.  

Lead author Prof Guy Boeckxstaens, a gastroenterologist at KU Leuven thinks this may point to a spectrum of food-related immune disorders. He said, “At one end of the spectrum, the immune response to a food antigen is very local, as in IBS. At the other end of the spectrum is food allergy, comprising a generalised condition of severe mast cell activation, with an impact on breathing, blood pressure, and so on.”

When researchers injected IBS-associated food antigens into the intestinal walls of IBS patients, they observed localised reactions similar to what they saw in the mice, and there were no reactions in healthy patients. Larger clinical trials will be needed to confirm these observations.

“This is further proof that the mechanism we have unraveled has clinical relevance,”  Prof Guy Boeckxstaens said. “But knowing the mechanism that leads to mast cell activation is crucial, and will lead to novel therapies for these patients,” he goes on. “Mast cells release many more compounds and mediators than just histamine, so if you can block the activation of these cells, I believe you will have a much more efficient therapy.”

Source: Medical Xpress

Journal information: Local immune response to food antigens drives meal-induced abdominal pain, Nature (2021). DOI: 10.1038/s41586-020-03118-2 , www.nature.com/articles/s41586-020-03118-2

New Research Links Bladder Pain Flare-ups to Pollen

High pollen counts have long been associated with allergic rhinitis with its well known symptoms such as itching eyes, running nose and sneezing, but now new research suggests that it may be aggravating a completely unexpected condition: chronic bladder pain.

In the United States, more than 10 million people are believed to suffer from urologic chronic pelvic pain syndrome (UCPPS) – a mysterious cluster of problems which include bladder pain syndrome and interstitial cystitis in women, chronic pelvic pain syndrome, and in men, chronic prostatitis.

Researchers regard it as “one of the most frustrating urologic conditions to understand and manage”, requiring a multidisciplinary and multimodal approach to management. However, it has been known to be associated with flare-ups of allergies, prompting Washington University epidemiologist Siobhan Sutcliffe to lead a team to investigate a possible connection. Their study recruited 290 participants diagnosed with UCPPS, and tracked pollen levels from three days before and on the day against UCPPS symptoms. Daily pollen counts did not correlate with UCPPS symptoms, but in participants with when pollen count was medium or high, there was a significant association with symptoms. The mast cell activation involved in pollen allergies release histamines which may be a contributing factor in UCPPS. Evidence for this comes from animal studies which have shown that exposure to histamine makes the bladder hypersensitive. Histamines also stays resident in the bladder longer than in the bloodstream as they are excreted via urine.

Sutcliffe said: “Our study provides evidence to suggest increased pollen counts may trigger symptom flares in people living with UCPPS.”This research may bring an avenue for some now forms of relief to UCPPS sufferers, but further research is needed to eliminate confounding factors, such as environmental factors associated with high pollen counts – strong levels of wind and thunderstorms may trigger pollen allergies but also exert some other kind of separate influence.

“Patients may benefit from taking antihistamines on days with high pollen levels, or from allergy testing and immunotherapy,” concluded Sutcliffe.

Source: Science Alert

Journal information: Javed I, Yu T, Li J et al. Does Pollen Trigger Urologic Chronic Pelvic Pain Syndrome Flares? A Case-Crossover Analysis in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network. Journal of Urology. 2020. doi:10.1097/ju.0000000000001482