Category: Allergies

Categories : Allergies COVIDTags :

Montelukast Can Block Harmful SARS-CoV-2 Protein and Protect Immune Cells

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Targeting Nsp1 with montelukast helps prevent shutdown of host protein synthesis Credit: Mohammad Afsar

Montelukast can bind to and block a crucial protein produced by SARS-CoV-2, reducing viral replication in human immune cells, according to a new study by researchers at the Indian Institute of Science (IISc).

Montelukast has been around for more than 20 years and is usually prescribed to reduce inflammation caused by conditions like asthma, hay fever and hives.

In the study, published in eLife, the researchers showed that the drug binds strongly to the C-terminal, which is one end of a SARS-CoV-2 protein called Nsp1, which is one of the first viral proteins unleashed inside human cells. NSp1 can bind to ribosomes inside immune cells, shutting down production of vital proteins that the immune system needs, thereby weakening it. Nsp1 could therefore be a target to reduce the virus’s damage.

“The mutation rate in this protein, especially the C-terminal region, is very low compared to the rest of the viral proteins,” explained IISc’s Assistant Professor Tanweer Hussain, senior author of the study. Since Nsp1 is unlikely to change in future variants, targeting it with drugs is a viable strategy, he added.

The researchers screened more than 1600 FDA-approved drugs with computational modelling to find the ones that bound strongly to Nsp1, coming up with a shortlist of drugs including montelukast and saquinavir, an anti-HIV drug. “The molecular dynamic simulations generate a lot of data, in the range of terabytes, and help to figure out the stability of the drug-bound protein molecule. To analyse these and identify which drugs may work inside the cell was a challenge,” said Mohammad Afsar, first author of the study.

The researchers then cultured human cells which produced Nsp1, treated them with montelukast and saquinavir separately, and found that only montelukast was able to rescue the inhibition of protein synthesis by Nsp1.

“There are two aspects [to consider]: one is affinity and the other is stability,” explained Afsar. This means that the drug needs to not only bind to the viral protein strongly, but also stay bound for a sufficiently long time to prevent the protein from affecting the host cell, he adds. “The anti-HIV drug (saquinavir) showed good affinity, but not good stability.” Montelukast, on the other hand, was found to bind strongly and stably to Nsp1, allowing the host cells to resume normal protein synthesis.

The researchers then tested the effect of the drug on live viruses and found that the drug was able to reduce viral numbers in infected cells in the culture.

“Clinicians have tried using the drug … and there are reports that said that montelukast reduced hospitalisation in COVID patients,” said A/Prof Hussain, adding that the exact mechanisms behind it still need to be fully understood. His team plans to work with chemists to see if they can modify the structure of the drug to increase its potency, and also plan to continue the hunt for more drugs.

Source: Indian Institute of Science

Categories : Allergies Cardiovascular DiseaseTags :

Allergies Linked to Increased Cardiovascular Risk

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Runny nose and sneezing symptoms
Photo by Britanny Colette on Unsplash

A national US health survey has revealed that adults with allergies are at an increased risk of hypertension and coronary heart disease, with the biggest risk increase seen in Black male adults. The study is presented at ACC Asia 2022 Together with the Korean Society of Cardiology Spring Conference.

“For patients with allergic disorders, routine evaluation of blood pressure and routine examination for coronary heart disease should be given by clinicians to ensure early treatments are given to those with hypertension or coronary heart disease,” said Yang Guo, PhD, the study’s lead author.

An association between allergic disorders and cardiovascular disease was detected in prior research, findings which remained controversial, Dr Guo explained. The present study sought to determine whether an increased cardiovascular risk exists in adults with allergic disorders.

The study used 2012 data from the National Health Interview Survey (NHIS), a cross-sectional survey of the US population. In the allergic group were adults with at least one allergic disorder, including asthma, respiratory allergy, digestive allergy, skin allergy and other allergy. The study included a total of 34 417 adults, over half of whom were women, average age 48.5 years. The allergic group included 10 045 adults. The researchers adjusted for age, sex, race, smoking, alcohol drinking and body mass index; they also examined subgroups stratified by demographic factors.

Having a history of allergic disorders was found to be associated with increased risk of developing hypertension and coronary heart disease. Further analysis showed that individuals with a history of allergic disorders between ages 18 and 57 had a higher risk of hypertension. An increased risk of coronary heart disease was seen in male Black/African American participants between ages 39-57. Asthma was the largest contributor of risk of hypertension and coronary heart disease.

Dr Guo said that to confirmed these findings, large cohort studies with long-term follow-up are required. Discovering the underlying mechanism could also help with management.

Source: American College of Cardiology

Categories : AllergiesTags :

Avoid Goat’s Milk Skin Products in Inflammatory Skin Conditions

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Individuals with inflammatory skin conditions should avoid using skincare products that contain food products such as goat’s milk, according to a series of case studies published in Clinical & Experimental Allergy. Such skincare products have been marketed to those with ‘sensitive skin’.

In children, milk allergy is one of the most common food allergies, but usually resolves in the first years of life. Adult-onset milk allergy is rare. In patients with inflammatory conditions of the skin such as atopic dermatitis, associations between the use of food allergen-containing skin products and systemic sensitisation to that foodstuff has been demonstrated for several foods. This is of concern, as food-containing skin products are commonly promoted as a safer and more ‘natural’ way of managing a variety of skin conditions. These are widely available for unprescribed purchase in pharmacies and supermarkets.

The present study reports on seven patients with inflammatory skin conditions who experienced anaphylaxis after ingesting goat’s or sheep’s milk or cheese products.  All of the patients had a history of using goat’s milk skin products to treat their skin conditions prior to the onset of their allergic reaction. Six of them had atopic dermatitis.

“Marketing of skin products derived from goat’s milk is extensive and targeted to patients with ‘sensitive skin’ who commonly have underlying inflammatory skin conditions,” the authors wrote. “Our findings provide novel evidence of the origins of adult-onset milk allergy and adds to the growing body of evidence that use of foodstuffs as therapy for inflammatory skin conditions can lead to the development of new food allergies.” 

Source: Wiley

Categories : Allergies PaediatricsTags :

Is Milk Allergy Being Overdiagnosed in Infants?

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Current guidelines could be causing cow’s milk allergy to be over-diagnosed in infants, according to a new study. 

Researchers analysed data on 1303 healthy infants who were exclusively breastfed until at least three months of age, and found that 38% and 74% of infants had multiple mild-to-moderate milk allergy symptoms – as defined by current allergy guidelines – at three months and 12 months old, respectively. By comparison, non-IgE-mediated cow’s milk allergy has a prevalence of less than 1% in children.

The researchers’ findings, which are published in Clinical & Experimental Allergy, suggest that following current guidelines may lead to over-diagnoses in infants by labelling normal infant symptoms as possible milk allergies.

“There is an assumption that the existence of a guideline is more beneficial than no guideline. However, well-meaning guidelines need to be supported by robust data to avoid harms from over-diagnosis that exceed the damage of missed and delayed cow’s milk allergy diagnoses that they are seeking to prevent,” the researchers wrote.

Source: Wiley

Categories : Allergies Mental HealthTags :

A Link Between Mental Health and Allergies

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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

Categories : Allergies PaediatricsTags :

A Third of Children with Food Allergies are Bullied

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Using a multi-question assessment, researchers found that 1 in 3 children with food allergies reported food allergy-related bullying, indicating the problem is more widespread than commonly believed.

For the study, reported in the Journal of Pediatric Psychology, children were asked a simple ‘yes’ or ‘no’ question about food allergy-related bullying, to which 17% of kids indicated they’d been bullied, teased or harassed about their food allergy. But when asked to reply to a multi-item list of victimisation behaviours, that number jumped to 31%. Furthermore, Children’s National Hospital researchers found that only 12% of parents reported being aware of it. 

The reported bullying ranged from verbal teasing or criticism to more overt acts such as an allergen being waved in their face or intentionally put in their food. Researchers say identifying accurate assessment methods for this problem are critical so children can get the help they need.

“Food allergy-related bullying can have a negative impact on a child’s quality of life. By using a more comprehensive assessment, we found that children with food allergies were bullied more than originally reported and parents may be in the dark about it,” says Linda Herbert, Ph.D., director of the Psychosocial Clinical and Research Program in the Division of Allergy and Immunology at Children’s National and one of the study’s researcher.

“The results of this study demonstrate a need for greater food allergy education and awareness of food allergy-related bullying among communities and schools where food allergy-related bullying is most likely to occur,” Dr Herbert added.

The study examined food allergy-related bullying and evaluated parent-child disagreement and bullying assessment methods. It included 121 children and 121 primary caregivers who completed questionnaires. The children ranged in age from 9 to 15 years of age and had an allergy diagnosis of one or more of the top eight IgE-mediated food allergies: peanut, tree nut, cow’s milk, egg, wheat, soy, shellfish and fish.

Of the 41 youth who reported food allergy-related bullying:

  • 51% reported experiencing overt physical acts such as an allergen being waved in their face, thrown at them or intentionally put in their food.
  • 66% reported bullying experiences including non-physical overt victimisation acts including verbal teasing, remarks or criticisms about their allergy and verbal threats or intimidation.
  • Eight reported relational bullying, such as rumour spreading, people speaking behind their back and being intentionally ignored or excluded due to their food allergy.

The researchers also note that food allergy bullying perpetrators included, but were not limited to, classmates and other students, and bullying most commonly occurred at school.

The authors found that only 12% of parents reported that their child had been bullied because of their food allergy and of those, 93% said their child had reported the bullying to them. Some parents even reported being made fun of or teased themselves because of concerns about their child’s food allergy.

“It’s important to find ways for children to open up about food allergy-related bullying,” Dr Herbert said. “Asking additional specific questions about peer experiences during clinic appointments will hopefully get children and caregivers the help and support they need.

Source: Children’s National Hospital

Categories : AllergiesTags :

New Allergen Pathway Discovery Could Yield New Meds

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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

Categories : AllergiesTags :

Allergies in Childhood Linked to Developing Tree Nut Allergies

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A Swedish study found that while allergic sensitivity to tree nuts was common in adults, most people never experienced symptoms.

Allergies to tree nuts are common and have become an important health concern as availability has increased. Tree nuts include hazelnuts, walnuts, pecans, cashews, pistachios, almonds, and brazil nuts.Tree nuts, as a group, are one of the eight most common allergens, and allergic reactions to them can be severe. Availability of tree nuts has increased both in the raw form and within processed foods and bakery products; tree nut utilisation has increased by 1kg per capita from 1980 to 2015. Research has shown that the consumption of nuts has positive cardiovascular effects, such as decreasing cholesterol, triglycerides, and fasting blood glucose, and this has encouraged consumption.

The study, with a total of 2215 participants, found that eczema, asthma, and egg allergies at an early age were associated with developing a tree nut allergy by adulthood. Additionally, the researchers found allergen molecules to be better diagnostic tools for predicting allergic symptoms to tree nuts compared with analysing allergen extracts. The study was published in Clinical and Experimental Allergy.

“This study increases the understanding of tree nut allergy in a general population, followed from infancy up to adulthood. For example, our study reveals that most extract‐based tree nut‐sensitised individuals do not have tree nut allergy and hence extract-based testing for tree nuts without a specific clinical suspicion should not be performed,” said co–lead author Jessica Bager, of the Karolinska Institute.

Source: Wiley

Categories : Allergies Diet and NutritionTags :

Common Probiotic Altered to Grow in Dairy Products

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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.

Categories : AllergiesTags :

Rollout of Peanut Allergy Treatment Stalled by Pandemic

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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