Discovery of how limiting damage from an asthma attack could stop disease

Scientists at King's College London have discovered a new cause for asthma that sparks hope for treatment that could prevent the life-threatening disease.

Most current asthma treatments stem from the idea that it is an inflammatory disease. Yet, the life-threatening feature of asthma is the attack or the constriction of airways, making breathing difficult. The new study, published today 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."

In the UK, 5.4 million people have asthma and can suffer from symptoms such as 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."

Dr Samantha Walker, Director of Research and Innovation at Asthma + Lung UK, said: "Only two per cent of public health funding is allocated to developing new treatments for the 12 million people living with lung conditions in the UK so new research that can help in the treatment or prevention of asthma is good news.

"This research using an experimental mouse model shows that constricting the airways leads to damage to the lung lining and inflammation, like that seen in asthma. It is this constriction and resulting damage that makes it difficult for people with asthma to breathe.

"Current medications for asthma work by treating the inflammation, but this isn't effective for everyone. Treatments aim to prevent future asthma attacks and improve asthma control by taking inhalers every day, but we know that ~31 per cent of people with asthma don't have treatment options that work for them, putting them at risk of potentially life-threatening asthma attacks.

"This discovery opens important new doors to explore possible new treatment options desperately needed for people with asthma rather than focusing solely on inflammation."

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.

Read more at Science Daily

Multiple air pollutants linked to asthma symptoms in children

Exposure to several combinations of toxic atmospheric pollutants may be triggering asthma symptoms among children, a recent analysis suggests.

The study, published in the journal Science of the Total Environment, showed that 25 different combinations of air pollutants were associated with asthma symptoms among 269 elementary school children diagnosed with asthma in Spokane, Washington. In line with previous research, the Washington State University-led study revealed a socioeconomic disparity -- with one group of children from a lower-income neighborhood exposed to more toxic combinations, a total of 13 of the 25 identified in this research.

"It's not just one pollutant that can be linked to asthma outcomes. This study examined the variety and combinations of air toxics that may be associated with asthma symptoms," said lead author Solmaz Amiri, a WSU researcher in the Elson S. Floyd College of Medicine.

While other studies have focused on a limited number of pollutants, Amiri and her colleagues used the data-crunching power of machine learning techniques to analyze the potential exposure effects of 109 air pollutants and their combinations on asthma outcomes.

The researchers drew on data collected and modeled by the Environmental Protection Agency on air toxics present in individual neighborhoods surrounding 10 Spokane elementary schools. They also accessed anonymized data from the elementary schools for reports of students diagnosed with asthma who experienced symptoms such as coughing, wheezing, difficulty breathing and the need to use an inhaler.

The study looked at asthma symptoms occurring in 2019 and 2020 in the six months before the pandemic lockdowns started in March 2020. The researchers then associated these data with air pollutant exposures that occurred within those six months and with two longer-term exposure periods of three years and five years prior to the asthma symptoms.

The researchers found that three specific pollutants were significantly associated with asthma symptoms across all three exposure periods.

The toxicants involved may have unfamiliar names -- 1,1,1 trichloroethane, 2-nitropropane and 2, 4, 6 trichlorophenol -- but they derive from commonly used materials. The first is a widely used solvent in industry but was formerly used in household cleaners and glues. The second is an additive to paints and other finishes, and the third is an anti-septic and anti-mildew agent that was banned in the 1980s but may still be found in some pesticides and preservatives made before then.

"Some of these air toxics were discontinued in the U.S., but they can still be found in materials that may be in storage or people have in their backyard or garage. Other air toxics still exist at least in the environment," said Amiri.

This study did not intend to pinpoint the source of any one air pollutant or the exact reason why one group of children from a lower-income neighborhood was highly exposed to air pollutants. However, proximity of known air pollution sources may play a role, Amiri said, such as living close to a highway with a lot of traffic or facilities that use solvents, such as paint producers or factories.

The finding of a likely socioeconomic disparity in air toxic exposures is consistent with previous research showing that children from lower-income areas, often indicated by schools with a higher percentage of students who qualify for free or reduced meals, are exposed to a wide variety of air pollutants in the neighborhoods where they live.

While the current study is limited to the mid-sized city of Spokane, Amiri noted that the findings align with another study in New York City which found similar air pollutants significantly associated with asthma outcomes.

"Both in Spokane and New York City, regardless of the setting -- how large or small the cities are -- these air toxics appear to be influencing asthma among children," she said.

Read more at Science Daily

Major breakthrough for severe asthma treatment

A landmark study has shown that severe asthma can be controlled using biologic therapies, without the addition of regular high-dose inhaled steroids which can have significant side effects.

The findings from the multinational SHAMAL study, published in The Lancet, demonstrated that 92% of patients using the biologic therapy benralizumab could safely reduce inhaled steroid dose and more than 60% could stop all use.

The study's results 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.

Asthma is one of the most common respiratory diseases worldwide -- affecting almost 300 million people -- and around 3 to 5% of these 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."

Benralizumab is a biologic therapy that reduces the number of inflammatory cells called eosinophil.

This is produced in abnormal numbers 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 and is available in specialist NHS asthma centres.

The SHAMAL study took place across 22 sites in four countries -- 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.

Read more at Science Daily

Burning candles and fumes from cooking is harmful for people with mild asthma

A cosy set table, a nice steak in the pan, and romantic candlelight may sound like the start of a lovely evening. However, a new study from the Department of Public Health at Aarhus University suggests that you should be cautious about inhaling too much of the cosy atmosphere. Karin Rosenkilde Laursen, a postdoc at the department 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 we turn on the oven, place a pan on the hob, or light candles, ultrafine particles and gases are produced, which we then inhale. 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.

Read more at Science Daily

Common origin behind major childhood allergies

Several major childhood allergies may all stem from the community of bacteria living in our gut, according to a new study led by researchers at the University of British Columbia and BC Children's Hospital.

The research, published in Nature Communications, identifies gut microbiome features and early life influences that are associated with children developing any of four common allergies -- eczema, asthma, food allergy and/or hay fever. The findings could lead to methods of predicting whether a child will develop allergies, and ways to prevent them from developing at all.

"We're seeing more and more children and families seeking help at the emergency department due to allergies," said Dr. Stuart Turvey, professor in the department of pediatrics at UBC and an investigator at BC Children's Hospital Research Institute, and co-senior author on the study. "Hundreds of millions of children worldwide suffer from allergies, including one in three children in Canada, and it's important to understand why this is happening and how it can be prevented."

The study is one of the first to examine four distinct school-aged pediatric allergies at once. While these allergic diseases each have unique symptoms, the Turvey lab was curious whether they might have a common origin linked to the infant gut microbiota composition.

"These are technically different diagnoses, each with their own list of symptoms, so most researchers tend to study them individually," says Dr. Charisse Petersen, co-senior author on the paper and postdoctoral fellow in the Turvey lab. "But when you look at what is going wrong at a cellular level, they actually have a lot in common."

For the study, researchers examined clinical assessments from 1,115 children who were tracked from birth to age five. Roughly half of the children (523) had no evidence of allergies at any time, while more than half (592) were diagnosed with one or more allergic disorders by an expert physician. The researchers evaluated the children's microbiomes from stool samples collected at clinical visits at three months and one year of age.

The stool samples revealed a bacterial signature that was associated with the children developing any of the four allergies by five years of age. The bacterial signature is a hallmark of dysbiosis, or an imbalanced gut microbiota, that likely resulted in a compromised intestinal lining and an elevated inflammatory response within the gut.

"Typically, our bodies tolerate the millions of bacteria living in our guts because they do so many good things for our health. Some of the ways we tolerate them are by keeping a strong barrier between them and our immune cells and by limiting inflammatory signals that would call those immune cells into action," says Courtney Hoskinson, a PhD candidate at UBC and first author on the paper. "We found a common breakdown in these mechanisms in babies prior to the development of allergies."

Many factors can shape the infant gut microbiota, including diet, how we are born, where we live, and our exposure to antibiotics. For example, antibiotics may wipe out sensitive bacteria, while breastfeeding tends to replenish and provide necessary food for bacteria in the infant gut. The researchers examined how these types of influences affected the balance of gut microbiota and the development of allergies.

"There are a lot of potential insights from this robust analysis," says Dr. Turvey. "From these data we can see that factors such as antibiotic usage in the first year of life are more likely to result in later allergic disorders, while breastfeeding for the first six months is protective. This was universal to all the allergic disorders we studied."

Now the researchers hope to leverage the findings to inform treatments that correct an imbalanced gut microbiota and could potentially prevent allergies from developing.

"Developing therapies that change these interactions during infancy may therefore prevent the development of all sorts of allergic diseases in childhood, which often last a lifetime," says Dr. Turvey.

The research is part of the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study that recruited families through BC Children's Hospital and BC Women's Hospital + Health Centre and other pediatric hospitals across Canada. Since launching in 2008, the team of Canadian researchers has tracked the health, growth and environments of kids from birth and made important discoveries about how asthma and allergies develop.

Read more at Science Daily

Study links adoption of electric vehicles with less air pollution and improved health

Electric vehicles are widely hailed as a key way to mitigate climate change through reduced emissions, but research on the dual benefits of reduced air pollution and improved health has been largely hypothetical.

A team of researchers from the Keck School of Medicine of USC have now begun to document the actual impact of electric vehicle adoption in the first study to use real-world data to link electric cars, air pollution and health. Leveraging publicly available datasets, the researchers analyzed a "natural experiment" occurring in California as residents in the state rapidly transitioned to electric cars, or light-duty zero emissions vehicles (ZEVs). The results were just published in the journal Science of the Total Environment.

The team compared data on total ZEV registration, air pollution levels and asthma-related emergency room visits across the state between 2013 to 2019. As ZEV adoption increased within a given zip code, local air pollution levels and emergency room visits dropped.

"When we think about the actions related to climate change, often it's on a global level," said Erika Garcia, PhD, MPH, an assistant professor of population and public health sciences at the Keck School of Medicine and the study's lead author. "But the idea that changes being made at the local level can improve the health of your own community could be a powerful message to the public and to policy makers."

The researchers also found that while total ZEVs increased over time, adoption was considerably slower in low-resource zip codes -- what the researchers refer to as the "adoption gap." That disparity points to an opportunity to restore environmental justice in communities that are disproportionately affected by pollution and related health problems.

"The impacts of climate change on health can be challenging to talk about because they can feel very scary," said Sandrah Eckel, PhD, an associate professor of population and public health sciences at the Keck School of Medicine and the study's senior author. "We're excited about shifting the conversation towards climate change mitigation and adaptation, and these results suggest that transitioning to ZEVs is a key piece of that."

Benefits for health and the climate

To study the effects of electric vehicle adoption, the research team analyzed and compared four different datasets. First, they obtained data on ZEVs (which includes battery electric, plug-in hybrid, and hydrogen fuel cell cars) from the California Department of Motor Vehicles and tabulated the total number registered in each zip code for every year between 2013 and 2019.

They also obtained data from U.S. Environmental Protection Agency air monitoring sites on levels of nitrogen dioxide (NO2), an air pollutant related to traffic, and zip code level asthma-related visits to the emergency room. Asthma is one of the health concerns long linked with air pollutants such as NO2, which can also cause and exacerbate other respiratory diseases, as well as problems with the heart, brain and other organ systems.

Finally, the researchers calculated the percentage of adults in each zip code who held bachelor's degrees. Educational attainment levels are frequently used as an indicator of a neighborhood's socioeconomic status.

At the zip code level, for every additional 20 ZEVs per 1,000 people, there was a 3.2% drop in the rate of asthma-related emergency visits and a small suggestive reduction in NO2 levels. On average across zip codes in the state, ZEVs increased from 1.4 to 14.6 per 1,000 people between 2013 and 2019. ZEV adoption was significantly lower in zip codes with lower levels of educational attainment. For example, a zip code with 17% of the population having a bachelor's degree had, on average, an annual increase of 0.70 ZEVs per 1,000 people compared to an annual increase of 3.6 ZEVs per 1,000 people for a zip code with 47% of the population having a bachelor's degree.

Past research has shown that underserved communities, such as lower-income neighborhoods, tend to face worse pollution and associated respiratory problems than more affluent areas. If ZEVs replace gas-powered cars in those neighborhoods, they could stand to benefit substantially.

"Should continuing research support our findings, we want to make sure that those communities that are overburdened with the traffic-related air pollution are truly benefiting from this climate mitigation effort," Garcia said.

More to learn

While climate change is a massive health threat, mitigating it offers a massive public health opportunity, Eckel said. As one of the first studies to quantify the real-world environmental and health benefits of ZEVs, the research can help demonstrate the power of this mitigation measure, including possibly reduced health care utilization and expenditures.

The findings are promising, Garcia said, but many questions remain. Future studies should consider additional impacts of ZEVs, including emissions related to brake and tire wear, mining of materials for their manufacture, and disposal of old cars. The researchers also hope to study additional types of pollutants and other classes of vehicles, in addition to conducting a follow-up study of the effects of the ever-growing share of ZEVs in the state.

Moving forward, transitioning to ZEVs is just one part of the solution, Eckel said. Shifting to public transport and active transport, including walking and biking, are other key ways to boost environmental and public health.

Read more at Science Daily

Potential long-term treatment for asthma found

A possible way to tackle one of the underlying causes of asthma has been developed by researchers from Aston University and Imperial College London.

In tests in mice, the researchers were able to virtually eliminate asthmatic symptoms within two weeks and return their airways to near normal.

Just under 5.5 million people in the UK receive treatment for asthma and around 1,200 people die of the disease each year.

Asthma causes the airways to become thickened and constricted, resulting in symptoms such as wheezing and shortness of breath.

Current treatments, including steroids, provide short term relief from these symptoms, by either relaxing the airways or reducing inflammation. However, no current drugs address the structural changes asthma makes to the airway and lungs, in order to offer a longer-lasting treatment.

Lead researcher, Dr Jill Johnson, from Aston University's School of Biosciences, said: "By targeting the changes in the airway directly, we hope this approach could eventually offer a more permanent and effective treatment than those already available, particularly for severe asthmatics who don't respond to steroids. However, our work is still at an early stage and further research is needed before we can begin to test this in people."

The research focused on a type of stem cell known as a pericyte, which is mainly found in the lining of blood vessels. When asthmatics have an allergic and inflammatory reaction, for example to house dust mites, this causes the pericytes to move to the airway walls. Once there, the pericytes develop into muscle cells and other cells that make the airway thicker and less flexible.

This movement of the pericytes is triggered by a protein known as CXCL12. The researchers used a molecule called LIT-927 to block the signal from this protein, by introducing it into the mice's nasal passages. Asthmatic mice that were treated with LIT-927 had a reduction in symptoms within one week and their symptoms virtually disappeared within two weeks. The researchers also found that the airway walls in mice treated with LIT-927 were much thinner than those in untreated mice, closer to those of healthy controls.

The team are now applying for further funding to carry out more research into dosage and timing, This would help them to determine when might be the most effective time to administer the treatment during the progress of the disease, how much of LIT-927 is needed, and to better understand its impact on lung function. They believe that, should this research be successful, it will still be several years before the treatment could be tested in people.

Read more at Science Daily

Ragweed allergy: Aggressiveness of pollen is determined by its place of origin and by the environment

The different geographic and climatic regions from which ragweed pollen originates, as well as the degree of environmental pollution, may influence the severity of allergic reactions such as hay fever and asthma. Pollen from plants in different areas exhibit different levels of aggressiveness. This is the conclusion reached by an inter-university study team led by MedUni Vienna and involving the University of Vienna and the University of Natural Resources and Applied Life Sciences. The study was recently published in the journal Frontiers in Allergy.

The research team developed an allergy model in which mice inhaled pollen from ragweed plants (Ambrosia artemisiifolia) collected in different geographic locations. They found that even a small amount of pollen (a total of 180 pollen grains) is sufficient to produce an allergic reaction, much less than the high pollen concentrations found in the air during the seasonal flowering period. As a result of climate change, the European flowering season is getting longer, and the plant is able to spread to more northerly areas. Furthermore, the regional origin of the pollen determines the severity of the allergic reaction it produces. The lead researcher and coordinator of the "Atopica" project, Michelle Epstein from MedUni Vienna, explained: "Our study shows that pollen from distinct environments can differ in its aggressiveness. So not only the concentration of the pollen in the air but also intrinsic changes (from within) related to the environment could alter the pollen's ability to sensitise and cause more severe allergic symptoms."

Wolfram Weckwerth, Professor at the Department of Functional and Evolutionary Ecology of the University of Vienna and one of the authors, said: "We now know that environmental factors change the aggressiveness of pollen. The next steps are further characterisation of the pollen, especially at the molecular level, to unambiguously identify the mixture of allergenic components." Anke Bellaire, a collaborator at the Department of Structural and Functional Botany at the Department of Botany and Biodiversity, University of Vienna, and also one of the authors, added: "Following these exciting results, we plan to continue ultrastructural subcellular analysis of ragweed pollen for further characterisation."

Gerhard Karrer, professor of botany at the University of Natural Resources and Applied Life Sciences, who was part of the team that collected the pollen in Austria, said: "The control of ragweed is a major public health concern and an adaptation strategy for mitigating and managing the impacts of climate change."

According to the researchers, there is a high probability that climate change and other environmental factors will also affect a number of other pollen-producing plants. This applied research model now provides a strategy for further studies investigating the impacts of climate change on pollen allergy.

33 million Europeans suffer from ragweed allergy

Ragweed (Ambrosia artemisiifolia) is a highly allergenic plant whose pollen causes hay fever in sensitized people and can lead to asthma. Currently, over 33 million Europeans suffer from ragweed allergy and researchers predict an increase to 77 million cases by 2060 as a result of climate change. The EU's annual economic burden of allergic asthma is already estimated to be as much as €151 billion. Ragweed is an invasive plant that is spreading particularly rapidly in Europe in the French Rhône Valley, in northern Italy, Hungary and Croatia. The season begins in August and extends throughout autumn. However, with global warming, the season is getting longer, and warmer temperatures will encourage ragweed plants to grow in more northerly areas and at higher altitudes. A single plant can produce about a billion grains of pollen per season, and these can travel over a thousand kilometres on the wind.

Read more at Science Daily

Air pollution caused 2,780 deaths, illnesses, and IQ loss in children in Massachusetts in 2019

Air pollution remains a silent killer in Massachusetts, responsible for an estimated 2,780 deaths a year and for measurable cognitive loss in Bay State children exposed to fine particulate pollutants in the air they breathe, according to a new study by researchers at Boston College's Global Observatory on Planetary Health.

The study was supported by the Barr Foundation and is the first to examine far-reaching public health consequences of air pollution in the state on a town-by-town basis. The study found air-pollution-related disease, death and IQ loss occur in every city and town regardless of demographics or income level. Highest rates were in the most economically disadvantaged and socially underserved cities and towns.

The Boston College team estimates the cumulative impact on childhood cognitive development in Massachusetts in 2019 was a loss of almost 2 million Performance IQ points, or more than 2 IQ points for the average child, according to the report, published today in the journal Environmental Health. IQ loss impairs children's school performance and reduces graduation rates, the team noted.

"We are talking about the impacts of air pollution at a very local level in Massachusetts -- not just statewide," said lead author Boston College Professor of Biology Philip J. Landrigan, MD, director of the Observatory. "This report gives the people in every city and town the opportunity to see for themselves the quality of the air they and their families are breathing and the dangerous health implications for both adults and children as a consequence of air pollution."

"All of these health effects occurred at pollution levels below current EPA standards," Landrigan noted.

The average level of fine particulate pollution across Massachusetts in 2019 was 6.3 micrograms per cubic meter, and levels ranged from a low of 2.77 micrograms per cubic meter in Worcester County to a high of 8.26 in Suffolk County. The U.S. Environmental Protection Agency standard is 12 micrograms per cubic meter, and the World Health Organization's recommended guideline is 5.

"Clearly, current EPA air pollution standards are not adequately protecting public health," Landrigan said.

Town-by-town air pollution information is not typically available, given there are not enough air quality monitoring stations in the state. The team determined levels for all cities and towns using available data and computer modeling.

While Massachusetts meets federal clean air guidelines and air pollution in the U.S. has declined 70 percent since the passage of the Clean Air Act in the 1970s -- when Landrigan and other scientists successfully pushed for the removal of lead from gasoline -- unclean air at current levels still poses health hazards to both healthy individuals and those with other ailments or illnesses.

"We do not have the level of air pollution you see in China or India and because it is mostly invisible today people tend to forget about air pollution and we get complacent," Landrigan said. "We hope to break through this complacency and increase awareness. Air pollution is killing 2,780 people in Massachusetts each year, nearly 5 percent of all deaths in the state, and that is a big deal. Air pollution is something we can fix. We know the steps that need to be taken to reduce fatalities and the impact on our children and grandchildren. Now citizens in every city and town across the Commonwealth need to urge our elected officials to take those necessary steps."

Additional findings include:
 

• Of the 2,780 deaths attributable to air pollution in Massachusetts in 2019, at least 2,185 were due to lung cancer 1,677 to heart disease, 343 to chronic lung disease, and 200 to stroke.
• Air pollution was responsible for 15,386 cases of pediatric asthma and an estimated 308 low-birthweight babies (5.5 lbs. or less).

More than 95 percent of air pollution in Massachusetts results from the combustion of fossil fuels. Cars, trucks, buses, planes, trains and ships produced two-thirds of pollutant emissions-655,000 tons -- in 2017, the most recent year for which data were available. Power plants, industrial facilities, and home heating and cooking produced 283,000 tons. In all, these sources emitted 938,000 tons of pollutants.

Fossil fuel combustion is also the major source of the carbon dioxide and other greenhouse gases that drive global climate change, which the researchers said should further incentivize Massachusetts to reduce air pollution and greenhouse gas emissions by transitioning to cleaner fuels.

"Air pollution harms our environment and young people, and these burdens disproportionately impact environmental justice communities," said Kathryn Wright, the Barr Foundation's Senior Program Officer for Clean Energy. "Meaningful action on climate change requires us to swiftly address air pollution from transportation and our energy system and its many harmful effects."

Fine particulate air pollution is linked to multiple non-communicable diseases in adults, including cardiovascular disease, stroke, lung cancer and diabetes. Among infants and children air pollution increases risk for premature birth, low birthweight, stillbirth, impaired lung development, and asthma.

"All of these adverse health effects occur at fine particulate matter pollution levels below the U.S. Environmental Protection Agency's current annual standard of 12 micrograms per cubic meter," said Landrigan. "So even for a state like Massachusetts, which registered below that standard, air pollution is a formidable public health threat that needs urgently to be addressed."

Read more at Science Daily

How exercise interventions could help people with asthma

Interventions aimed at promoting physical activity in people with asthma could improve their symptoms and quality of life -- according to new research from the University of East Anglia.

Researchers looked at whether interventions such as aerobic and strength or resistance training, had helped participants with asthma.

Although they found that these interventions worked, patients with asthma may have had difficulty undertaking them because of their difficulty travelling to fitness groups or because the interventions were not suitable for people with additional health conditions.

But the team say that digital interventions -- such as video appointments, smartwatches and mobile apps -- could remove some of these barriers and enable patients to carry out home-based programmes in future.

Prof Andrew Wilson, from UEA's Norwich Medical School, said: "Being physically active is widely recommended for people with asthma. Doing more than 150 minutes a week of moderate to vigorous physical activity has extensive benefits including improved lung function and asthma control.

"But research has shown that people living with asthma engage in less physical activity and are more sedentary than people without asthma.

"We wanted to find out whether interventions -- such as being asked to perform aerobic exercise a few times a week in group sessions, together with 'goal setting' -- are effective in helping people with asthma be more active."

The team studied interventions that were designed to promote physical activity in adults with asthma. They looked at 25 separate studies from around the world involving 1,849 participants with asthma, to see whether their symptoms and quality of life were changed thanks to the interventions.

Postgraduate researcher Leanne Tyson, also from UEA's Norwich Medical School said: "We found that interventions that promote physical activity had significant benefits in terms of increasing physical activity, decreasing time spent sedentary, improving quality of life, and decreasing asthma symptoms.

"This is really important because helping patients make significant behaviour changes could really improve their outcomes in the long term.

"Our review also highlights the potential use of digital interventions, which were notably absent.

"This is important now more than ever as patients have not been able to attend face-to-face support during the Covid-19 pandemic, and services will likely become overwhelmed. Therefore, alternative interventions and methods of delivery need to be considered."

Read more at Science Daily

When the western US burns, the east also gets sick

While most of the largest U.S. wildfires occur in the Western U.S., almost three-quarters of the smoke-related deaths and visits to the emergency room for asthma occur east of the Rocky Mountains.

Smoke exposure, whether from wildfires or local burning, contributes to health problems across the U.S., but the impacts vary by region. A new study finds that smoke contributes to a larger percentage of health problems in the West, but affects greater numbers of people in the East -- possibly when they aren't even aware of the smoky air.

The new study was published in GeoHealth, AGU's journal investigating the intersection of human and planetary health for a sustainable future.

In the West, where population density is generally lower and smoke concentrations are typically higher, smoke played a larger role in the number of asthma complaints and ER visits, contributing to more than 1% of annual visits in some years. In the East, with its high population density and lower smoke concentrations, there were a higher number of visits overall, even though a smaller percentage were related to smoke (0.3% to 0.6%).

The researchers estimate that long-term smoke exposure results in about 6,300 extra deaths each year, with the highest numbers occurring in the most populous states. Only 1,700 of those deaths occurred in the West.

Fires throw tremendous amounts of pollutants into the air, including toxic gases and soot. Smoke contains tiny particles smaller than 2.5 microns, called PM2.5, that enter the lungs and contribute to multiple health problems. Short-term exposure to PM2.5 from smoke is linked to respiratory health problems, like asthma attacks, and the long-term effects of PM2.5 from smoke are not fully understood. Research on PM2.5 from urban pollution suggests that exposure is linked to lung cancer, heart disease and an overall higher chance of death.

"Large wildfires are projected to increase in frequency and burned area in the Western U.S. Because of that, and projected decreases in urban-sourced PM2.5, fires are expected to become the dominant source of PM2.5 in the U.S. by the end of the century," said atmospheric scientist and first author Katelyn O'Dell. O'Dell was formerly a graduate student at Colorado State University but is now a postdoctoral researcher at George Washington University. "We wanted to study the impacts of wildfire smoke specifically on health so we can better prepare for that future, when we expect to have more smoke in our lives."

O'Dell collaborated with epidemiologists at Colorado State University to perform a health impact assessment. The researchers estimated the fraction of asthma ER visits and hospitalizations resulting from PM2.5 in smoke across the country from 2006 to 2018. They used existing data on asthma hospital visits and daily local estimates of PM2.5 based on readings from instruments at ground level and satellite data showing the location of smoke in the atmosphere.

The new study also included the first analysis of the health impacts of 18 hazardous air pollutants (HAPs) present in smoke, such as formaldehyde and benzene. The researchers determined that HAPs are likely a less important but more uncertain factor than PM2.5 in the health problems caused by smoke exposure.

As smoke pollution is likely to increase, the researchers argue that the U.S. needs better national smoke forecasting and alerts so that people in downwind regions know when to take precautions like wearing a mask, limiting time outside and using indoor air purifiers.

"We talk about smoke in the West so much, but we don't often talk about smoke in the East," O'Dell said. "I wonder if there's a lack of awareness because you think, 'Oh, that's a Western problem.'"

O'Dell emphasized that their study didn't determine the source of the smoke affecting each region and that local burning and Canadian fires also contribute to smoky air in the Eastern U.S. She said that establishing the source of the smoke impacting health in each region is an important next step.

Tarik Benmarhnia, a climate change epidemiologist at the University of California, San Diego, who was not involved in the study, agreed that we need better smoke warning systems, especially for farm workers and others who labor outside. He pointed out that while smoke plumes impact entire regions, they don't affect all residents equally. Age, race, ethnicity, exposure to other types of air pollution -- such as from traffic -- and pre-existing health conditions can all put a person at higher risk of developing health problems from smoke. He said that future research should investigate these disparities.

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Firefighters found to have persistent lung damage from Fort McMurray wildfire

Firefighters at the centre of the battle against the massive Fort McMurray wildfire in 2016 have persistent lung damage, according to new findings published by a University of Alberta occupational health research team.

"Those who were dealing with burning organic matter were exposed to a barrage of small particles in the smoke, and the ones with the highest exposure have long-term consequences," said principal investigator Nicola Cherry, an occupational epidemiologist, professor of medicine and Tripartite Chair of Occupational Health in the Faculty of Medicine & Dentistry.

The firefighters had more than double the risk of developing asthma compared with the general population. They also exhibited a number of changes in lung function tests supportive of an effect on the lungs, including greater lung hyperreactivity and increased thickening of the bronchial wall.

"The impact was correlated to exposure -- those who had more exposure had more effects," said Cherry.

For three years after the fire, Cherry's team followed 1,234 Alberta firefighters.The firefighters' exposure to fire-related particles was estimated based on the hours they worked on the blaze, the dates they were there, the firefighting tasks they were performing, and Alberta Environment estimates of particulate matter at different locations.

The Fort McMurray fire broke out in May 2016 and was under control by the fall, but it was not officially declared out until the following year. The highest exposure to particulate matter happened during the first week, Cherry said. Firefighters were deployed from across Alberta from crews that specialize in structural fires (i.e., buildings), oil and gas industry fires and wildland fires.

Many did not have sufficient supplies of specialized lung protection equipment or were not able to wear it while fighting the Fort McMurray fire, Cherry said.

"It was an extraordinarily violent fire," she said. "It's very difficult to rush uphill pulling equipment behind you if you have a heavy mask on that doesn't let you breathe."

Cherry modelled her study, which was funded by the Canadian Institutes for Health Research and the Government of Alberta, on studies that examined the respiratory health of first responders following the World Trade Center collapse in New York City in September 2001.

"It's not easy to do this kind of study during a catastrophe," said Cherry, who had serendipitously taken delivery of a mobile lung assessment lab the week before the Fort McMurray fire broke out.

"At the World Trade Center, the exposure was mainly to inorganic dust, whereas in Fort McMurray it was burning vegetation, as well as buildings," Cherry said. "It's interesting that we saw similar results from very different exposure."

Cherry's research team looked at three main sources of evidence about the lung health of the firefighters before and after the fire. First, they asked for permission to link to their administrative health record, which showed doctor's visits and diagnoses. The records for each firefighter were matched with five patients from the general population of similar age, sex, geographic location and health status as a control group for comparison.

The team also measured the firefighters' lung function, which shows how much air goes in and out of the lungs. Finally, some of the firefighters with no history of chronic respiratory disease or smoking were randomly selected for clinical followup, including CT scans of their lungs and methacholine challenge testing, used to check for asthma.

This is one of several papers Cherry has published on the mental and physical health of the Fort McMurray firefighters.

"They take enormous risks," she said. "This study shows clearly that it is possible for exposures to cause changes in the lung that don't get better over time."

Cherry said she will continue to study the occupational health of firefighters -- including crews currently fighting wildfires in the interior of British Columbia and Alberta -- in hopes of recommending ways to make the work safer. She is studying whether wearing a mask or washing skin more often could reduce exposure to chemicals from smoke. Putting more crews through shorter rotations at fire scenes might also help to lessen health impacts, she said.

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First months decisive for immune system development

Many diseases caused by a dysregulated immune system, such as allergies, asthma and autoimmunity, can be traced back to events in the first few months after birth. To date, the mechanisms behind the development of the immune system have not been fully understood. Now, researchers at Karolinska Institutet show a connection between breast milk, beneficial gut bacteria and the development of the immune system. The study is published in Cell.

"A possible application of our results is a preventative method for reducing the risk of allergies, asthma and autoimmune disease later in life by helping the immune system to establish its regulatory mechanisms," says the paper's last author Petter Brodin, paediatrician and researcher at the Department of Women's and Children's Health, Karolinska Institutet. "We also believe that certain mechanisms that the study identifies can eventually lead to other types of treatment for such diseases, not just a prophylactic."

The incidence of autoimmune diseases such as asthma, type 1 diabetes and Crohn's disease is increasing in children and adolescents in parts of the world. These diseases are debilitating, but not as common in low-income countries as they are in Europe and the USA.

It has long been known that the risk of developing these diseases is largely determined by early life events; for instance, there is a correlation between the early use of antibiotics and a higher risk of asthma. It is also known that breastfeeding protects against most of these disorders.

There is a link between specific, protective bacteria on the skin and in the airways and gut and a lower risk of immunological diseases. However, there is still much to learn about how these bacteria form the immune system.

Researchers at Karolinska Institutet, Evolve Biosystems, Inc, the University of California Davis, University of Nebraska, Lincoln, and University of Nevada, Reno studied how the neonatal immune system adapts to and is shaped by the many bacteria, viruses, nutrients and other environmental factors to which the baby is exposed during the first few months of life.

Earlier research has shown that bifidobacteria are common in breastfed babies in countries with a low incidence of autoimmune diseases.

Breast milk is rich in HMOs (Human milk oligosaccharides), which babies are unable to metabolise on their own. The production of these complex sugars are instead associated with the evolutionary advantage of nourishing specific gut bacteria that play an important part in their immune system. Bifidobacteria are one such bacterial class.

"We found that babies whose intestinal flora can break down HMOs have less inflammation in the blood and gut," says professor Brodin. "This is probably because of the uniquely good ability of the bifidobacteria to break down HMOs, to expand in nursing babies and to have a beneficial effect on the developing immune system early in life."

Babies who were breastfed and received additional bifidobacteria had higher intestinal levels of the molecules ILA and Galectin-1. ILA (indole-3-lactic acid) is needed to convert HMO molecules into nutrition; Galectin-1 is central to the activation of the immune response to threats and attacks.

According to the researchers, Galectin-1 is a newly discovered and critical mechanism for preserving bacteria with beneficial, anti-inflammatory properties in the intestinal flora.

The results are based on 208 breastfed babies born at Karolinska University Hospital between 2014 and 2019. The researchers also used novel methods to analyse the immune system even from small blood samples. Additionally, a second cohort developed by the University of California in which infants were exclusively breastfed and half were fed B. infantis supplement were analyzed for enteric inflammation.

One limitation of the study is that the researchers were unable to study the immune system direct in the gut and had to resort to blood samples. Not all aspects of the gut immune system can be seen in the blood, but it is not ethically defensible to take intestinal biopsies from healthy neonates.

The researchers now hope to follow the participant babies for a longer time to see which ones develop atopic eczema, asthma and allergies.

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Increased meat consumption associated with symptoms of childhood asthma

 Substances present in cooked meats are associated with increased wheezing in children, Mount Sinai researchers report. Their study, published in Thorax, highlights pro-inflammatory compounds called advanced glycation end-products (AGEs) as an example of early dietary risk factors that may have broad clinical and public health implications for the prevention of inflammatory airway disease.

Asthma prevalence among children in the United States has risen over the last few decades. Researchers found that dietary habits established earlier in life may be associated with wheezing and potentially the future development of asthma.

Researchers examined 4,388 children between 2 and 17 years old from the 2003-2006 National Health and Nutrition Examination Survey (NHANES), a program of the National Center for Health Statistics, which is part of the U.S. Centers for Disease Control and Prevention. It is designed to evaluate the health and nutritional status of adults and children in the United States through interviews and physical examinations.

The researchers used NHANES survey data to evaluate associations between dietary AGE and meat consumption frequencies, and respiratory symptoms. They found that higher AGE intake was significantly associated with increased odds of wheezing, importantly including wheezing that disrupted sleep and exercise, and that required prescription medication. Similarly, higher intake of non-seafood meats was associated with wheeze-disrupted sleep and wheezing that required prescription medication.

"We found that higher consumption of dietary AGEs, which are largely derived from intake of non-seafood meats, was associated with increased risk of wheezing in children, regardless of overall diet quality or an established diagnosis of asthma," said Jing Gennie Wang, MD, lead author of the study, and a former fellow in Pulmonary, Critical Care and Sleep Medicine at the Icahn School of Medicine at Mount Sinai.

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Follow your gut: How farms protect from childhood asthma

 We are born into an environment full of small organisms called microbiota. Within the first minutes and hours of our lives, they start challenging but also educating our immune system. The largest immune organ is our gut, where maturation of the immune system and maturation of the colonizing bacteria, the gut microbiome, go hand in hand. After profound perturbations in the first year of life, the maturation process, the composition of the gut microbiome gradually stabilizes and accompanies us for our lives. Previous research of the Munich scientists showed an asthma-protective effect by a diverse environmental microbiome, which was particularly pronounced in farm children. The question now was whether this effect could be attributed to the maturation process of the early gut microbiome.

Farm life boosts gut microbiome maturation in children The researchers analyzed fecal samples from more than 700 infants partly growing up on traditional farms between the age of 2 and 12 months who took part in PASTURE -- a European birth cohort, which runs for almost 20 years now with funding from the European Commission.

"We found that a comparatively large part of the protective farm effect on childhood asthma was mediated by the maturation of the gut microbiome in the first year of life" states Dr. Martin Depner, biostatistician at Helmholtz Zentrum München, and further concludes: "This suggests that farm children are in contact with environmental factors possibly environmental microbiota that interact with the gut microbiome and lead to this protective effect."

The researchers anticipated effects of nutrition on the gut microbiome maturation but were surprised to find strong effects of farm-related exposures such as stays in animal sheds. This emphasizes the importance of the environment for the protective effect. In addition, vaginal delivery and breastfeeding fostered a protective microbiome in the first two months of life.

Furthermore, the researchers discovered an inverse association of asthma with measured level of fecal butyrate. Butyrate is a short chain fatty acid which is known to have an asthma protective effect in mice. The researchers concluded that gut bacteria such as Roseburia and Coprococcus with the potential of producing short chain fatty acids may contribute to asthma protection in humans as well. Children with a matured gut microbiome showed a higher amount of these bacteria (Roseburia and Coprococcus) compared to other children.

"Our study provides further evidence that the gut may have an influence on the health of the lung. A mature gut microbiome with a high level of short chain fatty acids had a protective effect on the respiratory health of the children in this study. This suggests the idea of a relevant gut-lung axis in humans," says Dr. Markus Ege, professor for clinical-respiratory epidemiology at the Dr. von Hauner Children's Hospital. "This also means, however, that an immature gut microbiome may contribute to the development of diseases. This emphasizes the need for prevention strategies in the first year of life, when the gut microbiome is highly plastic and amenable to modification."

Probiotic prevention strategies The researchers demonstrated that the asthma protective effect is not dependent on one single bacteria only, but on the maturation of the entire gut microbiome. This finding questions the approach of using single bacteria as probiotics for the prevention of asthma. Probiotics should rather be tested with respect to their sustained effect on the compositional structure of the gut microbiome and its maturation early in life.

Further studies on cow milk Nutritional aspects analyzed in this study may serve as prevention strategies such as consumption of cow's milk. Unprocessed raw milk, however, cannot be recommended because of the risk of life-threatening infections such as EHEC. Scientists at the Dr. von Hauner Children's Hospital are currently running a clinical trial on the effects of minimally processed but microbiologically safe milk for the prevention of asthma and allergies (MARTHA trial).

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Asthma and allergies more common in teens who stay up late

Teenagers who prefer to stay up late and wake later in the morning are more likely to suffer with asthma and allergies compared to those who sleep and wake earlier, according to a study published in ERJ Open Research. [1]

Asthma symptoms are known to be strongly linked to the body's internal clock, but this is the first study to look at how individual sleep preferences influence asthma risk in teenagers.

Researchers say the study reinforces the importance of sleep timing for teenagers and opens up a new channel of research in to how sleep affects teenagers' respiratory health.

The study was led by Dr Subhabrata Moitra from the division of pulmonary medicine at the University of Alberta, Canada, who carried out the research while at the Barcelona Institute for Global Health, Spain. He said: "Asthma and allergic diseases are common in children and adolescents across the world and the prevalence is increasing. We know some of the reasons for this increase, such as exposure to pollution and tobacco smoke, but we still need to find out more.

"Sleep and the 'sleep hormone' melatonin are known to influence asthma, so we wanted to see if adolescents' preference for staying up late or going to bed early could be involved in their asthma risk."

The study involved 1,684 adolescents living in West Bengal, India, aged 13 or 14 years, who were taking part in the Prevalence and Risk Factors of Asthma and Allergy-Related Diseases among Adolescents (PERFORMANCE) study.

Each participant was asked about any wheezing, asthma, or symptoms of allergic rhinitis, such as a runny nose and sneezing. They were asked a series of questions to judge whether they were 'evening types', 'morning types' or in between, such as what time of the evening or night they tend to feel tired, when they would choose to wake up, and how tired they feel first thing in the morning.

Researchers compared the teenagers' symptoms with their sleep preferences, taking into account other factors that are known to affects asthma and allergies, such as where the participants live and whether their family members smoke.

They found that the chance of having asthma was around three times higher in teens who prefer to sleep later compared to those who preferred to sleep earlier. They also found the risk of suffering allergic rhinitis was twice as high in late-sleepers compared to early-sleepers.

Dr Moitra adds: "Our results suggest there's a link between preferred sleep time, and asthma and allergies in teenagers. We can't be certain that staying up late is causing asthma, but we know that the sleep hormone melatonin is often out of sync in late-sleepers and that could, in turn, be influencing teenagers allergic response.

"We also know that children and young people are increasingly exposed to the light from mobile phone, tablets, and other devices, and staying up later at night. It could be that encouraging teenagers to put down their devices and get to bed a little earlier would help decrease the risk of asthma and allergies. That's something that we need to study more."

A second phase of the PERFORMANCE study is scheduled in 2028-29, which means it will be possible to repeat the study with a new group of teenagers to see if there has been any change in teenagers sleeping habits and their respiratory health. Dr Moitra and his team also hope to quantify their findings by taking objective measurements of participants' lung function and sleep time.

Professor Thierry Troosters is President of the European Respiratory Society and was not involved in the research. He said: "We need to know much more about why asthma and allergies are rising in children and teenager and, hopefully, find ways to reduce these conditions.

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Scientists uncover immune cells that may lower airway allergy and asthma risk

The world is full of house dust mites. Do some cleaning, and you'll probably stir some up. While everyone has immune cells capable of reacting to common allergens like house dust mites, most of us have no allergic symptoms.

Still, many people do react with the typical allergic symptoms: sneezing, a runny nose, and itchy, swollen nasal passages. Others have a much more severe reaction: a life-threatening asthma attack.

To treat the root cause of allergies and asthma, researchers need to know exactly what sets these patients apart from healthy individuals.

In a new Science Immunology study, published on June 12, 2020, scientists at La Jolla Institute for Immunology (LJI) offer a clue to why non-allergic people don't have a strong reaction to house dust mites. They've uncovered a previously unknown subset of T cells that may control allergic immune reactions and asthma from ever developing in response to house dust mites -- and other possible allergens.

"We discovered new immune cell subsets and new therapeutic opportunities," says Grégory Seumois, Ph.D., instructor and director of LJI's Sequencing Core and co-leader of the new study. "This new population of cells could be one, out of many unknown mechanisms, that explains why healthy people don't develop inflammation when they breathe in allergens."

"The study highlights the power of unbiased single-cell genomics approaches to uncover novel biology," says LJI Professor Pandurangan Vijayanand, M.D. Ph.D., senior author of the new study.

The study builds on the Vijayanand lab's expertise in linking gene expression to disease development. The team also took advantage of the Immune Epitope Database, an LJI-led resource that houses information on how the immune system interacts with allergens like house dust mites.

Why house dust mites? These microscopic critters are hard to avoid, which means nearly everyone has been exposed. Even in people without a house dust mite (HDM) allergy, the immune system is likely to react in some way as it learns to recognize HDM molecules. This makes HDM a useful model for studying what causes allergies and asthma attacks.

The LJI team used a technique part of the "genomic revolution" arsenal of tools, called single-cell RNA-seq (or single cell transcriptomics) to see exactly which genes and molecules specific T cells produce in response to HDM allergens. They tested cells from four groups of people: people with asthma and HDM allergy, people with asthma but no HDM allergy, people with only HDM allergy, and healthy subjects.

Their analysis suggests that a subset of helper T cells, called interleukin (IL)-9 Th2 expressing HDM-reactive cells, is more prevalent in the blood of people with HDM-allergic asthma compared with those who are only allergic to HDM. Further analysis suggested that those IL9-TH2 cells are enriched in a group of molecules/genes that increased the cytotoxic potential of those cells. In other words, those specific T cells could kill other cells and drive inflammation.

In contrast, another subset of T cells stood out in the non-allergic subjects. These T cells express an "interferon response signature" and were enriched for a gene that encodes a protein called TRAIL. The work done by Seumois and his colleagues suggest that TRAIL could be important because it could dampen the activation of helper T cells.

This finding may mean that people with this specific cell population could have less T-cell driven inflammation in response to HDM allergens. At last, this could provide a clue to why some people develop allergies and asthma while others do not.

"Now if functional studies confirm this dampening effect, we're curious if there is a way to boost the activation of these T cells or induce their proliferation in asthmatic or allergic populations," says Seumois. "Can we act on those cells very early on, before asthma has developed?"

For example, genomics studies like this one may someday help identify children at risk of developing asthma and allergies. Early detection could open the door to preemptively acting on immune cells before development of allergy and asthma.

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Evidence in mice that childhood asthma is influenced by the neurotransmitter dopamine

Neurons that produce the neurotransmitter dopamine communicate with T cells to enhance allergic inflammation in the lungs of young mice but not older mice, researchers report November 19 in the journal Immunity. The findings potentially explain why asthma susceptibility is higher in children than in adults. By highlighting the important role of interactions between the nervous system and the immune system in childhood asthma, the results could lead to new strategies for treating the common chronic disease.

"This is the first study that reveals a contribution of age-related nerve-T cell communication to susceptibility to the development of asthma in young children," says senior study author Xingbin Ai, a Harvard researcher at Brigham & Women's Hospital and Massachusetts General Hospital. "Since asthma often starts in early childhood, we believe that the identification of disease mechanisms unique to young age will provide novel therapeutic targets for early intervention of asthma."

Asthma is a potentially life-threatening chronic condition that intermittently inflames and narrows the airways in the lungs, causing wheezing, chest tightness, shortness of breath, and coughing. Although medical treatment and management of environmental triggers can help control symptoms, there is currently no cure for the disease. In the United States, asthma affects more than 26 million people, including an estimated 6 million children. In fact, it is one of the most common long-term diseases of childhood.

Ai and colleagues suspected that the nervous system, which communicates with the immune system to regulate inflammation, might explain the high prevalence of asthma in children. As the nervous system continues to develop after birth, neurons may modulate tissue inflammation in an age-related manner.

In the new study, Ai and colleagues investigated the role of the developing nervous system in asthma characterizing early age. The researchers discovered that sympathetic nerves innervating the mouse lung primarily produced dopamine in early postnatal life but another neurotransmitter called norepinephrine in adult life. A similar pattern was evident when they compared lung and lymph node tissues from children up to 13 years of age and adults ranging in age from 40 to 65 years.

In addition, the researchers found that dopamine released by sympathetic nerves innervating the lung binds to the dopamine neurotransmitter receptor on CD4+ T helper cells to promote their differentiation into asthma-exacerbating Th2 cells, thereby enhancing lung inflammation. By contrast, norepinephrine-producing nerves in the adult lung had no such effect. Importantly, the findings reveal the similarity between mice and humans in terms of the innervation of dopamine-producing nerves in the early lung and the T cell response to dopamine.

In mouse models of allergen exposure, the dopamine-DRD4 pathway significantly increased Th2 cell inflammation in the lung tissue of neonatal mice, reducing mucus overproduction and airway hyper-responsiveness. By contrast, these effects were either not evident or much weaker in adult mice exposed to allergens.

Taken together, these findings demonstrate that the dopamine-DRD4 signaling between sympathetic nerves and CD4+ T helper cells in the lung plays an important role in augmenting allergic inflammation in early life. By facilitating inflammation, dopamine-producing nerves may endow the early lung with a mechanism of tissue repair following infection, which may be advantageous when the lung is immature and vulnerable to pathogens.

"Our findings provide evidence for the involvement of the communication between nerves and immune cells in susceptibility to asthma in early life," Ai says. "It is important to emphasize that simply generically blocking the nerve-immune cell communication is not a good solution, as nerves play important roles in regulating functions of the airway, such as breathing. We will need to identify more specific pathways along the nerve-immune cell axis for therapeutic targeting."

Toward this goal, the researchers will set out to identify druggable targets to disrupt the nerve-T cell communication that goes awry upon allergen exposure. They will also evaluate whether this age-related communication impacts the progression of asthma from childhood to adulthood, and if so, how disease progression can be prevented. Another avenue of future research will be to investigate how allergen exposure and viral infection may affect nerve development in the lung, thereby triggering asthma in children.

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