Tag: asthma

Categories : Respiratory DiseasesTags :

First New Treatment for Asthma Attacks in 50 Years

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An injection given during some asthma and COPD attacks was shown to be more effective than the current treatment of steroid tablets, reducing the need for further treatment by 30%. The findings, published in The Lancet Respiratory Medicine, could be “game-changing” for millions of people with asthma and COPD around the world, scientists say.

The type of symptom flare-up the injection treats are called ‘eosinophilic exacerbations’ and involve symptoms such as wheezing, coughing and chest tightness due to inflammation resulting from high amounts of eosinophils, a type of white blood cell. Eosinophilic exacerbations make up to 30% of COPD flare-ups and almost 50% of asthma attacks. They can become more frequent as the disease progresses, leading to irreversible lung damage in some cases.

Treatment at the point of an exacerbation for this type of asthma has barely changed for over fifty years, with steroid drugs being the mainstay of medication. Steroids such as prednisolone can reduce inflammation in the lungs but have severe side-effects such as diabetes and osteoporosis. Furthermore, many patients ‘fail’ treatment and need repeated courses of steroids, re-hospitalisation or die within 90 days.

Results from the phase two clinical trial ABRA study, led by scientists from King’s College London and sponsored by the University of Oxford, show a drug already available can be re-purposed in emergency settings to reduce the need for further treatment and hospitalisations. The multi-centre trial was conducted at Oxford University Hospitals NHS Foundation Trust and Guy’s and St Thomas’ NHS Foundation Trust.

Benralizamab is a monoclonal antibody which targets eosinophils to reduce lung inflammation. It is currently used for the treatment of severe asthma. The ABRA trial has found a single dose can be more effective when injected at the point of exacerbation compared to steroid tablets.

The study investigators randomised people at high risk of an asthma or COPD attack into three groups, one receiving benralizumab injection and dummy tablets, one receiving standard of care (prednisolone 30mg daily for five days) and dummy injection and the third group receiving both benralizumab injection and standard of care. As a double-blind, double-dummy, active-comparator placebo-controlled trial, neither the people in the study, or the study investigators knew which study arm or treatment they were given.

After 28 days, respiratory symptoms of cough, wheeze, breathlessness and sputum were found to be better with benralizumab. After 90 days, there were four times fewer people in the benralizumab group that failed treatment compared to standard of care with prednisolone.

Treatment with the benralizumab injection took longer to fail, meaning fewer episodes to see a doctor or go to hospital. Quality of life also improved for people with asthma and COPD.

This could be a game-changer for people with asthma and COPD. Treatment for asthma and COPD exacerbations have not changed in fifty years despite causing 3.8 million deaths worldwide a year combined.

– Lead investigator of the trial Professor Mona Bafadhel from King’s Centre for Lung Health

She added: “Benralizumab is a safe and effective drug already used to manage severe asthma. We’ve used the drug in a different way – at the point of an exacerbation – to show that it’s more effective than steroid tablets which is the only treatment currently available. The big advance in the ABRA study is the finding that targeted therapy works in asthma and COPD attacks. Instead of giving everyone the same treatment, we found targeting the highest risk patients with very targeted treatment, with the right level of inflammation was much better than guessing what treatment they needed.”

The benralizumab injection was administered by healthcare professionals in the study but can be potentially administered in the GP practice or in the Emergency Department. Benralizumab was safe in the study and similar in safety to many past studies.

Professor Mona Bafadhel said, “We hope these pivotal studies will change how asthma and COPD exacerbations are treated for the future, ultimately improving the health for over a billion people living with asthma and COPD across the world.”

Source: King’s College London

Categories : Paediatrics Respiratory DiseasesTags :

Signs of Developing Asthma are Evident in the First Year of Life

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Respiratory tract. Credit: Scientific Animations CC4.0

What factors lead to chronic respiratory disease? Researchers investigated this question using health data from about 780 infants. Their analysis, published in The Lancet Digital Health, shows that children’s risk of developing asthma later in life can be more reliably predicted by observing the dynamic development of symptoms during the first year of life.

Genetic predisposition, passive smoking, high levels of air pollution and infections are only a few of the risk factors for asthma. Each factor has only a small influence on its own. It is their interplay that makes asthma more likely, according to the hypothesis of an international research committee, of which Professor Urs Frey of the University of Basel and the University Children’s Hospital Basel is a member.

Together with Dr Uri Nahum from his team and international colleagues, Frey investigated how the interaction of these factors during the course of the first year of life affected children’s developing respiratory systems. The analysis was based on health data from two cohorts, amounting to around 780 healthy infants born in various European countries.

A new way of looking at chronic illness

For both cohorts the researchers calculated the network of interactions between a range of known risk factors for every week of each child’s life, and then compared these with the appearance of symptoms such as coughing or wheezing. “Observing this interaction of risk factors in the context of dynamic development over time is a new way of looking at chronic illnesses,” underlines Frey. It is a case of watching the developing lungs adapting to their environment.

And it was exactly this, the adaptation of the lungs, that differentiated the group of children who developed asthma at between two and six years of age from those who had not developed it by the time they started school (generally at six years old in Switzerland). “It’s a nice, practical example of the value of digital health data, which were first quantified mathematically using these kinds of dynamic network analyses,” says Frey.

The findings cannot yet be used for early diagnosis in individual children. However, according to Frey: “With greater amounts of data and machine learning, it would certainly be conceivable to calculate a risk profile for individual children in the future.” Nowadays, digital health data is relatively easy to collect with the help of smartphone apps.

Source: University of Basel

Categories : Obstetrics & Gynaecology Respiratory DiseasesTags :

Higher Odds of Miscarriage, Needing Fertility Treatment for Women with Asthma

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Women who are being treated for asthma are more likely to miscarry and need fertility treatment to get pregnant, according to a large study presented at the European Respiratory Society (ERS) Congress in Vienna, Austria. The study also suggests that most women with asthma are able to have babies.

The study was presented by Dr Anne Vejen Hansen from the department of respiratory medicine at Copenhagen University Hospital, Denmark.

She said: “Asthma is common in women of reproductive age. Previous studies have shown that it takes women with asthma longer to get pregnant than those without asthma when undergoing fertility treatment, and that asthmatic women who succeed in getting pregnant have more often had fertility treatment than non-asthmatic women. But most existing studies are on women who have actually got pregnant, so we wanted to examine fertility outcomes on a national scale, to also include those that might not become pregnant at all.”

The team analysed reproductive outcomes for all Danish women born from 1976 to 1999, following them from 1994 to 2017. In total, 769,880 women were included and followed; anyone who took anti-asthma medication on a regular basis was classified as asthmatic.

They found that women with asthma experienced a higher degree of foetal loss compared to women without asthma (17.0% vs. 15.7%) and more use of fertility treatment (5.6% vs. 5.0%). However, the proportion who subsequently gave birth was 77% in women with and without asthma, suggesting that asthma does not seem to affect the number of live births.

Dr Vejen Hansen said: “We found that women fulfilling the definition of asthma had a higher rate of foetal loss and an increased use of fertility treatment. The more severe the asthma and the more flare ups the women experienced, the more likely they were to need fertility treatment. Why this is, is not clear. It might be related to systemic inflammation throughout the body, including women’s reproductive organs.

“But the numbers also show that these same women who redeem asthma medication still have as many live births in the end as women who don’t. This suggests that most women with asthma probably do manage to become pregnant and have babies in the end.

“We also plan to investigate the possible effect of male asthma on fertility, and, therefore, have another similar registry-based study in the pipeline.”

Professor Lena Uller is Chair of the ERS group on Airway Pharmacology and Treatment and Head of the Respiratory Immunopharmacology research group at Lund University, Sweden, and was not involved in the research. She said: “It’s reassuring that women seem to have the same live birth rate regardless of their asthma. However, the results also indicate that women with asthma should take into consideration potential reproductive challenges in their family planning. If women with asthma are worried about their fertility, they should speak to their doctor.

“The results of this study also underscore the importance of managing asthma in reproductive-aged women. The fact that the more severe the asthma, the more the problems with fertility, suggests that uncontrolled asthma is the problem and we should be helping women to get their asthma under control.”

Source: European Respiratory Society

Categories : Environmental Effects Respiratory DiseasesTags :

Extreme Heat Linked to Children’s Asthma Hospital Visits

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For children seeking care at a California urban paediatric health centre, extreme heat events were associated with increased asthma hospital visits, according to research published at the ATS 2024 International Conference.

“We found that both daily high heat events and extreme temperatures that lasted several days increased the risk of asthma hospital visits,” said corresponding author Morgan Ye, MPH, research data analyst, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco School of Medicine. “Understanding the impacts of climate-sensitive events such as extreme heat on a vulnerable population is the key to reducing the burden of disease due to climate change.”

Ms Ye and colleagues looked at 2017-2020 electronic health records from the UCSF Benioff Children’s Hospital Oakland, which included data on asthma hospital visits by patients of the hospital, some of whom are from Benioff Oakland’s Federally Qualified Health Center, and demographics including patients’ zip codes. They used data from the PRISM Climate Group of Oregon State University to determine the timing of daily maximum (daytime heat waves) and minimum (nighttime heat waves) for each zip code. The researchers restricted their analyses to the region’s warm season (June to September). To evaluate the potential range of effects of different heat wave measurements, they used 18 different heat wave definitions, including the 99th, 97.5th and 95th percentile of the total distribution of the study period for one, two or three days.

They designed the study in a way that allowed them to determine the association between each heat wave definition and a hospital visit. They repeated the analysis for Bay Area and Central California zip codes.

The team discovered that daytime heat waves were significantly associated with 19% higher odds of children’s asthma hospital visits, and longer duration of heat waves doubled the odds of hospital visits. They did not observe any associations for night-time heat waves.

According to Ye, “We continue to see global temperatures rise due to human-generated climate change, and we can expect a rise in health-related issues as we observe longer, more frequent and severe heat waves. Our research suggests that higher temperatures and increased duration of these high heat days are associated with increased risk of hospital visits due to asthma. Children and families with lower adaptation capacity will experience most of the burden. Therefore, it is important to obtain a better understanding of these heat-associated health risks and susceptible populations for future surveillance and targeted interventions.”

The authors note that past research has suggested positive associations between extreme heat and asthma, but findings regarding hospitalisations and emergency room visits have been conflicting. Additionally, many other studies have focused on respiratory hospitalizations and not hospitalizations for asthma, specifically, and have not included or had a focus on children. This study is also unique because it investigated the effect of daily high temperatures but also the effects of persistent extreme temperatures.

The San Francisco Bay Area and California overall are unique areas of interest because the state is considered a coastal region with less prevalence of cooling units, such as air conditioners. While temperatures may not reach the extremes experienced in other parts of the country, this study demonstrates that even milder extreme heat temperatures may significantly impact health. These effects are more pronounced in climate-susceptible populations, including children and those who are medically vulnerable, such as those served by the urban paediatric health centre in this study. The authors hope these study results will lead to more equitable health outcomes and reduce racial/ethnic disparities observed in climate-sensitive events.

“These results can be used to inform targeted actions and resources for vulnerable children and alleviate health-related stress during heat waves,” they conclude.

Source: American Thoracic Society

Categories : Respiratory DiseasesTags :

Limiting the Damage from an Asthma Attack could Halt the Disease

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Scientists at King’s College London have discovered that the features of asthma attacks, a disease usually treated as being inflammatory, in fact stem from constriction of airways, making breathing difficult. The new study, published in Science, shows for the first time that many features of an asthma attack – inflammation, mucus secretion, and damage to the airway barrier that prevents infections – result from this mechanical constriction in a mouse model.

The findings suggest that blocking a process that normally causes epithelial cell death could prevent the damage, inflammation, and mucus that result from an asthma attack.

Professor Jody Rosenblatt from King’s College London said: “Our discovery is the culmination of more than ten years work. As cell biologists who watch processes, we could see that the physical constriction of an asthma attack causes widespread destruction of the airway barrier. Without this barrier, asthma sufferers are far more likely to get long-term inflammation, wound healing, and infections that cause more attacks. By understanding this fundamental mechanism, we are now in a better position to prevent all these events.”

Asthma symptoms include wheezing, coughing, feeling breathlessness and a tight chest. Triggers such as pollen or dust can make asthma symptoms worse and can lead to a life-threatening asthma attack.

Despite the disease commonality, the causes of asthma are still not understood. Current medications treat the consequences of an asthma attack by opening the airways, calming inflammation, and breaking up the sticky mucus which clogs the airway, which help control asthma, but do not prevent it.

The answer to stopping asthma symptoms may lie in cell extrusion, a process the researchers discovered that drives most epithelial cell death. Scientists used mouse lung models and human airway tissue to discover that when the airways contract, known as bronchoconstriction, the epithelial cells that line the airway get squeezed out to later die.

Because bronchoconstriction causes so many cell extrusions, it damages the airway barrier which causes inflammation and excess mucus.

In previous studies, the scientists found that the chemical compound gadolinium can block extrusion. In this study, they found it could work in mice to prevent the excess extrusion that causes damage and inflammation after an asthma attack. The authors note that gadolinium has not been tested in humans and has not been deemed to be safe or efficacious.

Professor Rosenblatt said: “This constriction and destruction of the airways causes the post-attack inflammation and excess mucus secretion that makes it difficult for people with asthma to breathe.

“Current therapies do not prevent this destruction – an inhaler such as Albuterol opens the airways, which is critical to breathing but, dishearteningly, we found it does not prevent the damage and the symptoms that follow an attack. Fortunately, we found that we can use an inexpensive compound, gadolinium which is frequently used for MRI imaging, to stop the airway damage in mice models as well as the ensuing inflammation and mucus secretion. Preventing this damage could then prevent the build-up of musculature that cause future attacks.”

Professor Chris Brightling from the University of Leicester and one of the co-authors of the study said: “In the last decade there has been tremendous progress in therapies for asthma particularly directed towards airway inflammation. However, there remains ongoing symptoms and attacks in many people with asthma. This study identifies a new process known as epithelial extrusion whereby damage to the lining of the airway occurs as a consequence of mechanical constriction and can drive many of the key features of asthma. Better understanding of this process is likely to lead to new therapies for asthma.”

The discovery of the mechanics behind cell extrusion could underlie other inflammatory diseases that also feature constriction such as cramping of the gut and inflammatory bowel disease.

Source: King’s College London

Categories : AllergiesTags :

Asthma Drug Omalizumab can Limit Allergic Reactions to Foods

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An existing biologic drug, omalizumab, can make life safer for children with food allergies by preventing dangerous allergic responses to small quantities of allergy-triggering foods, according to a new study led by scientists at the Stanford School of Medicine.

The findings, published in the New England Journal of Medicine, suggest that regular use of omalizumab could protect people from severe allergic responses, such as difficulty breathing, if they accidentally eat a small amount of a food they are allergic to.

“I’m excited that we have a promising new treatment for multifood allergic patients. This new approach showed really great responses for many of the foods that trigger their allergies,” said the study’s senior author, Sharon Chinthrajah, MD, associate professor of medicine and of pediatrics, and the acting director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford Medicine.

“Patients impacted by food allergies face a daily threat of life-threatening reactions due to accidental exposures,” said the study’s lead author, Robert Wood, MD, professor of pediatrics at Johns Hopkins University School of Medicine. “The study showed that omalizumab can be a layer of protection against small, accidental exposures.”

Omalizumab, which the Food and Drug Administration originally approved to treat diseases such as allergic asthma and chronic hives, binds to and inactivates the antibodies that cause many kinds of allergic disease. Based on the data collected in the new study, the FDA approved omalizumab for reducing risk of allergic reactions to foods on Feb. 16.

All study participants were severely allergic to peanuts and at least two other foods. After four months of monthly or bimonthly omalizumab injections, two-thirds of the 118 participants receiving the drug safely ate small amounts of their allergy-triggering foods. Notably, 38.4% of the study participants were younger than 6 years, an age group at high risk from accidental ingestions of allergy-triggering foods.

Allergies are common

Food allergies affect about 8% of children and 10% of adults in the United States. People with severe allergies are advised to fully avoid foods containing their allergy triggers, but common allergens such as peanuts, milk, eggs and wheat can be hidden in so many places that everyday activities such as attending parties and eating in restaurants can be challenging.

“Food allergies have significant social and psychological impacts, including the threat of allergic reactions upon accidental exposures, some of which can be life-threatening,” Chinthrajah said. Families also face economic impacts from purchasing more expensive foods to avoid allergens, she added.

In the best available treatment for food allergies, called oral immunotherapy, patients ingest tiny, gradually increasing doses of allergy-triggering foods under a doctor’s supervision to build tolerance. But oral immunotherapy itself can trigger allergic responses, desensitization to allergens can take months or years, and the process is especially lengthy for people with several food allergies, as they are usually treated for one allergy at a time. Once they are desensitised to an allergen, patients also must continue to eat the food regularly to maintain their tolerance to it – but people often dislike foods they were long required to avoid.

“There is a real need for treatment that goes beyond vigilance and offers choices for our food allergic patients,” Chinthrajah said.

Omalizumab is an injected antibody that binds and deactivates all types of immunoglobin E, or IgE, the allergy-causing molecule in the blood and on the body’s immune cells. So far, omalizumab appears able to provide relief from multiple food allergens at once.

“We think it should have the same impact regardless of what food it is,” Chinthrajah said.

Injections stave off severe reactions

The study included 177 children with at least three food allergies each, of whom 38% were 1 to 5 years old, 37% were 6 to 11 years old, and 24% were 12 or older. Participants’ severe food allergies were verified by skin-prick testing and food challenges; they reacted to less than 100 milligrams of peanut protein and less than 300 milligrams of each other food.

Two-thirds of the participants were randomly assigned to receive omalizumab injections, and one-third received an injected placebo; the injections took place over 16 weeks. Medication doses were set based on each participant’s body weight and IgE levels, with injections given once every two or four weeks, depending on the dose needed. The participants were re-tested between weeks 16 and 20 to see how much of each allergy-triggering food they could safely tolerate.

Upon re-testing, 79 patients (66.9%) who had taken omalizumab could tolerate at least 600 mg of peanut protein, the amount in two or three peanuts, compared with only four patients (6.8%) who had the placebo. Similar proportions of patients showed improvement in their reactions to the other foods in the study.

About 80% of patients taking omalizumab were able to consume small amounts of at least one allergy-triggering food without inducing an allergenic reaction, 69% of patients could consume small amounts of two allergenic foods and 47% could eat small amounts of all three allergenic foods.

Omalizumab was safe and did not cause side effects, other than some instances of minor reactions at the site of injection. This study marks the first time its safety has been assessed in children as young as 1.

More questions

More research is needed to further understand how omalizumab could help people with food allergies, the researchers said.

“We have a lot of unanswered questions: How long do patients need to take this drug? Have we permanently changed the immune system? What factors predict which people will have the strongest response?” Chinthrajah said. “We don’t know yet.”

The team is planning studies to answer these questions and others, such as finding what type of monitoring would be needed to determine when a patient gains meaningful tolerance to an allergy-triggering food.

Many patients who have food allergies also experience other allergic conditions treated by omalizumab, Chinthrajah noted, such as asthma, allergic rhinitis (hay fever and allergies to environmental triggers such as mold, dogs or cats, or dust mites) or eczema. “One drug that could improve all of their allergic conditions is exactly what we’re hoping for,” she said.

The drug could be especially helpful for young children with severe food allergies, she added, because they tend to put things in their mouths and may not understand the dangers their allergies pose, she added.

The drug could also make it safer for community physicians to treat food allergy patients, since it cannot trigger dangerous allergic reactions, as oral immunotherapy sometimes does. “This is something that our food allergy community has been waiting a long time for,” Chinthrajah said. “It’s an easy drug regimen to implement in a medical practice, and many allergists are already using this for other allergic conditions.”

Source: Stanford Medicine

Categories : Paediatrics Respiratory DiseasesTags :

Appeasing the Wheezing: Determinants and Outcomes of Respiratory Disease in Childhood

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Asthma and cystic fibrosis are diseases which affect the lungs of children and adults. Previous research has shown that genetic and environmental factors during pregnancy and early childhood can contribute to the way children and young adults are affected by these lung diseases.

In her thesis, Emma Caffrey Osvald, PhD student at Karolinska Institutet looked for new factors that may influence the development and outcomes of asthma and cystic fibrosis. In the four included studies, Emma used data from a clinical cohort and national health and demographic registers and a quality register on individuals born in Sweden to shed light on potential factors which impact the course of asthma and cystic fibrosis. Her findings should be useful when creating clinical guidelines and policies for the prevention and management of respiratory disease in children and young adults.

What are the most important results in your thesis?

“In my first study, we show that mothers with asthma have an increased likelihood of having a child with asthma and that higher lung function in pregnancy is associated with a decreased likelihood of having a child with asthma. However, asthma or lung function in the mother does not impact childhood growth. In the second study, we see that parental social standing (socioeconomic status, measured as parents’ education and income) is associated with the onset of asthma in childhood. By comparing the social standing and onset of asthma among first cousins we see that parental education may be directly linked to the onset of asthma. In the third study, we also show that there is a connection between having asthma in childhood or young adulthood and death between 1 to 25 years of age. The likelihood of death between 1 to 25 years of age is higher if the person also has a life-limiting disease but not altered by the parents social standing at the child’s birth. In the final study, we see some association between low parental social standing and severe disease and lung function decline among persons with cystic fibrosis, however low parental social standing does not impact growth. So we found that there are factors in the parents (including during the pregnancy and social standing) which impacts the onset of asthma. Asthma increases the risk of mortality between 1 to 25 years and low parental social standing is shown to be associated with severe disease and lung function decline in persons with cystic fibrosis.”

Why did you become interested in this topic?

“I have wanted to learn more about epidemiology ever since my ex-job project as a medical student and these PhD projects have allowed me, as a paediatric pulmonologist, to explore the factors which influence onset and outcomes for children and young adults with respiratory disease. Asthma and CF are two chronic diseases which we meet as part of our routine clinical practice and for me it has been really interesting to avail of both clinical data and national register data and a variety of statistical methods to further our understanding of these diseases.“

What do you think should be done in future research?

“Areas which will interest me in my future research continues to be the determinants and outcomes of respiratory disease in childhood. For me, the future of register-based research lies in the combining of clinical data with register data. There is more to explore in regards to risk factors for acute respiratory disease such as severe pneumonia and empyema, but also the outcomes for persons with asthma and CF, such as presence of comorbidity or educational attainment.”

Doctoral thesis: Appeasing the wheezing: determinants and outcomes of respiratory disease in childhood.

Source: Karolinska Institutet

Categories : Respiratory DiseasesTags :

Biologics Alone may be Able to Control Severe Asthma

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A European study showed that 92% of patients using the biologic therapy benralizumab could safely reduce inhaled steroid dose and more than 60% could cease entirely. The results, published in The Lancet, could be transformative for severe asthma patients by minimising or eliminating the unpleasant, and often serious, side effects of inhaled steroids.

These include osteoporosis which leads to increased risk of fractures, diabetes and cataracts.

Around 3 to 5% of the 300 million people with asthma worldwide have severe asthma. This leads to daily symptoms of breathlessness, chest tightness and cough, along with repeated asthma attacks which require frequent hospitalisation.

The SHAMAL study was led by Professor David Jackson, head of the Severe Asthma Centre at Guy’s and St Thomas’ and Professor of Respiratory Medicine at King’s College London.

Professor Jackson said: “Biological therapies such as benralizumab have revolutionised severe asthma care in many ways, and the results of this study show for the first time that steroid related harm can be avoided for the majority of patients using this therapy.”

The monoclonal antibody benralizumab targets interleukin-5, reducing eosinophil count, which is elevated in the airway of patients with severe asthma and is critically involved in the development of asthma attacks.

Benralizumab is injected every four to eight weeks.

The SHAMAL study took place across 22 sites in the UK, France, Italy and Germany.

The 208 patients were randomly assigned to taper their high dose inhaled steroid by varying amounts over 32 weeks, followed by a 16 week maintenance period.

Approximately 90% of patients experienced no worsening of asthma symptoms and remained free of any exacerbations throughout the 48 week study.

Similar studies to SHAMAL will be necessary before firm recommendations can be made regarding the safety and efficacy of reducing or eliminating high dose steroid use with other biologic therapies.

Source: King’s College London

Categories : Respiratory DiseasesTags :

A Hard-to-treat Subtype of Asthma in Older Men

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Scientists have uncovered a group of T cells that may drive severe asthma, which gather in the lungs and seem most harmful in men who develop asthma in later life. The new research, published in MED, suggests asthma patients with these cells in their lungs may be more likely to have hard-to-treat, and potentially fatal, asthma attacks. These cells do not respond to the usual general therapy for asthma patients.

The scientists, from the University of Southampton and La Jolla Institute for Immunology (LJI), in California, uncovered these T cells, called ‘cytotoxic CD4+ tissue-resident memory T cells’, thanks to volunteers enrolled in the NHS clinic-based WATCH study. It follows hundreds of asthma patients of different ages, sexes, and disease severities. By following patients over many years, and analysing their immune cell populations, researchers are making new connections between asthma symptoms and immune cell activity.

“If you are male and you develop asthma after age 40, there’s a high chance this T cell population is in your lungs,” says LJI Research Assistant Professor Gregory Seumois, who co-led the study with LJI Professor Pandurangan Vijayanand.

“Once you understand the role of cells like these T cells better, you can start to develop treatments that target those cells,” says WATCH study director Dr Ramesh Kurukulaaratchy, Associate Professor at the University of Southampton and researcher at the NIHR Southampton Biomedical Research Centre.

Scientists now hope to learn more about these cells and their role in asthma development in order to develop personalised therapies for asthma patients.

How harmful T cells drive asthma

The ‘memory’ T cells help protect the body from viruses and bacteria it has encountered before, but the same T cell memory is a big problem for asthma patients. Their misguided T cells see harmless molecules, such as pollen, and produce a dangerous inflammatory response.

Men who developed asthma later in life had an overwhelming number of these potentially harmful T cells. Their lungs should have been home to a diverse bunch of CD4+ T cell types but, in this group, more than 65% of their cells were cytotoxic CD4+ tissue-resident memory T cells.

Personalised asthma treatments

Single-cell RNA sequencing by LJI scientists provides a ‘biomarker’ to help detect cytotoxic CD4+ tissue-resident memory T cells in more patients going forward.

Finding this biomarker represents a “paradigm shift” in asthma research, says Dr Kurukulaaratchy. Before now, scientists and clinicians separated asthma patients into just two groups: ‘T2 high’ and T2 low’. In a study published earlier this year, the research team showed the importance of drilling down to identify many more asthma patient subgroups; their analysis reveals that 93% of WATCH subjects with severe asthma were in the T2 high category.

Study co-author Professor Hasan Arshad, Chair in Allergy and Clinical Immunology at the University of Southampton, researcher at the NIHR Southampton Biomedical Research Centre, and Director of The David Hide Asthma and Allergy Research Centre, Isle of Wight says: “We have to think of severe asthma as having different subtypes, and the treatment has to be tailored according to these subtypes because one size does not fit all.”

The researchers now want to use sequencing tools and other techniques to discover additional biomarkers and asthma patient subtypes.

Source: University of Southampton

Categories : Environmental Effects Respiratory DiseasesTags :

Burning Candles and Cooking Fumes are Harmful for People with Mild Asthma

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A new study from Aarhus University has shown that young people with mild asthma can experience inflammation and irritation from candles as well as cooking fumes. The results, published in Particle and Fibre Toxicology, suggest that asthma sufferers should try and reduce exposure, for example by opening kitchen windows while cooking.

For this randomised controlled double-blind exposure study, exposed 36 young asthmatics to three different exposures in the climate chambers at Aarhus University. They were exposed to emissions from cooking, emissions from burning candles and finally clean air. Each time, the participants were exposed for five hours under highly controlled conditions. Particles and gases were measured during exposures, and participants reported symptoms related to irritation and general well-being. Biomarkers in relation to airway and systemic inflammatory changes were assessed before exposure, immediately after exposure and again the next morning.

Karin Rosenkilde Laursen, a postdoc at the university’s Department of Public Health and co-author of the study, says:

“Our study shows that indoor air pollution caused by fumes from cooking and burning candles can lead to adverse health effects such as irritation and inflammation in young individuals with mild asthma. Among other things, we’ve found indications of DNA damage and signs of inflammation in the blood.”

When ovens are turned, pans put on the hob, or candles are lit, particulate matter and gases are produced, which can be inhaled. Previous studies have shown that these particles and gases can be detrimental to health. What sets this study apart is that the researchers have focused on the effects on young individuals with mild asthma, aged between 18 and 25, says Karin Rosenkilde Laursen:

“In the study, we observed that even very young individuals with mild asthma can experience discomfort and adverse effects if the room is not adequately ventilated during cooking or when burning candles. Young people are generally fitter and more resilient than older and middle-aged individuals. Therefore, it is concerning that we observed a significant impact from the particles on this particularly young age group.”

But not only people diagnosed with asthma need to keep an eye on the indoor climate, she says.

“Even though the study focused on young asthmatics, its findings are interesting and relevant for all of us. Winter is approaching, a time when we tend to light many candles and perhaps are less likely to open doors and windows while cooking. By prioritising a healthier indoor climate, even when we’re cosying up indoors, we may be able to help reduce the incidence of serious lung and cardiovascular diseases, as well as cancer.”

Karin Rosenkilde Laursen plans to follow up this study with another examining how emissions from cooking and candles affect healthy adults.

Source: Aarhus University