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girl with asthma inhaler

Children’s National becomes part of CAUSE Network

girl with asthma inhaler

Seven clinical sites in six different cities will join forces to perform mechanistic and translational studies examining the basic immunology of pediatric asthma among urban, under-resourced and largely minority children and adolescents.

The National Institute of Allergy and Infectious Diseases (NIAID) allocated $10 million in funding to establish the Childhood Asthma in the Urban Setting (CAUSE) network. The NIAID plans to increase this number by $70 million over seven years to support the network. Children’s National Hospital will be part of the new research network, which is a 7-year consortium comprising of seven clinical sites in six different cities that will join forces to perform mechanistic and translational studies examining the basic immunology of pediatric asthma among urban, under-resourced and largely minority children and adolescents.

Children’s National is the home of Improving Pediatric Asthma Care in the District of Columbia (IMPACT DC). The program focuses on research, care and advocacy to decrease asthma morbidity experienced by at-risk youth in the region while serving as a model program for the nation. NIAID gave an initial $3 million to IMPACT DC to conduct its own pilot study of anti-IgE therapy to prevent asthma exacerbations. Additional support for this and other studies will come from subcontracts from the CAUSE Coordinating Center at the University of Wisconsin in Madison.

“This new award allows IMPACT DC to remain part of one of the nation’s most prestigious pediatric asthma research consortia,” said Stephen Teach, M.D, M.P.H., chair for the Department of Pediatrics at George Washington University School of Medicine and Health Sciences. “It will allow us to both pursue an independent research agenda while collaborating with similar academic centers nationwide.”

Pediatric asthma is the most common chronic disease in children, and it is estimated that about 6.1 million children under 18 years suffer from this condition. It disproportionately affects urban, minority and under-resourced children and adolescents.

“It is essential to develop an understanding of the basic immunology of the disease and therapeutic options to ameliorating these disparities,” said Dr. Teach.

CAUSE researchers will explore the mechanisms of immune tolerance to allergens, the role of early environmental exposures in the pathogenesis of asthma, the pathogenesis and mechanisms of non-atopic asthma, the role of the respiratory epithelium in asthma and more.

The CAUSE network comprises of seven clinical research centers, including Children’s National led by principal investigator, Dr. Teach, and the following research centers:

  • Boston Children’s Hospital. Principal investigators: Wanda Phipatanakul, M.D., and Talal Chatila, M.D.
  • Cincinnati Children’s Hospital Medical Center. Principal investigator: Gurjit Khurana Hershey, M.D., Ph.D.
  • Columbia University Health Sciences, New York. Principal investigator: Meyer Kattan, M.D.
  • Icahn School of Medicine at Mount Sinai, New York. Principal investigators: Paula Busse, M.D., Supinda Bunyavanich, M.D., and Juan Wisnivesky, M.D.
  • Lurie Children’s Hospital of Chicago. Principal investigators: Rajesh Kumar, M.D., and Jacqueline Pongracic, M.D.
  • University of Colorado Denver. Principal investigator: Andrew Liu, M.D.
illustration of lungs with coronavirus inside

Pediatric asthma exacerbations during the COVID-19 pandemic

illustration of lungs with coronavirus inside

The authors found that in 2020, the District of Columbia did not experience the typical “September asthma epidemic” of exacerbations seen in past years.

In the United States, pediatric asthma exacerbations typically peak in the fall due to seasonal factors such as increased spread of common respiratory viruses, increased exposure to indoor aeroallergens, changing outdoor aeroallergen exposures and colder weather. In early 2020, measures enacted to reduce spread of the coronavirus (COVID-19) — such as social distancing, quarantines and school closures — also reduced pediatric respiratory illnesses and asthma morbidity. Children’s National Hospital immunologist and allergist William J. Sheehan, M.D., and colleagues sought to determine if these measures also affected the 2020 fall seasonal asthma exacerbation peak in Washington, D.C.

The authors found that in 2020, the District of Columbia did not experience the typical “September asthma epidemic” of exacerbations seen in past years. Emergency department visits, hospitalizations and intensive care unit admissions for asthma during the 2020 fall season were significantly reduced compared to previous years.

The authors conclude that, “this is likely due to social distancing, quarantines and school closures enacted during the pandemic. This is a small silver lining in a very difficult year. As 2021 brings optimism for gradual improvements of the pandemic, careful monitoring is necessary to recognize and prepare for childhood asthma morbidity to return to pre-pandemic levels.”

Additional study authors include: Shilpa J. Patel, M.D., M.P.H., Rachel H.F. Margolis, Ph.D., Eduardo R. Fox, M.D., Deborah Q. Shelef, M.P.H., Nikita Kachroo, B.S., Dinesh Pillai, M.D. and Stephen J. Teach, M.D., M.P.H.

Read the full study in the Journal of Allergy and Clinical Immunology: In Practice.

Asthma-Related Healthcare Utilization by Month

Asthma-Related Healthcare Utilization by Month (2016-2020). Asthma-related emergency department (ED) visits, hospitalizations and pediatric intensive care unit (PICU) admissions over time by month between 2016 and 2020. The p-values are for comparisons of mean monthly numbers for fall seasons of 2016-2019 to fall season of 2020. Image courtesy of the Journal of Allergy and Clinical Immunology: In Practice.

doctor helping child with asthma

New guidelines advance treatment approach for children with asthma

doctor helping child with asthma

Patients with asthma will benefit from new recommendations from a team of national asthma experts.

Patients with asthma will benefit from new recommendations from a team of national asthma experts that includes Stephen Teach, M.D., M.P.H., director and principal investigator of the IMPACT DC Asthma Clinic at Children’s National HospitalThe new guidance, published in the Journal of Allergy and Clinical Immunology, represents the first update to federal comprehensive asthma management and treatment guidelines in more than a decade.

The new recommendations are based on systematic reviews conducted by the Agency for Healthcare Research and Quality, input from National Asthma Education Prevention Program participant organizations and a 19-member expert panel consisting of medical experts and the public.

“The updated guidelines touch on several management issues of critical importance to children, families, and clinicians struggling with the most common chronic disease of childhood,” says Dr. Teach. “Being a part of this expert panel allowed me to advocate for the unique needs of pediatric patients, especially those from under-resourced environments.”

The focused updates provide new guidance for six areas:

  • Using inhaled corticosteroids when needed for recurrent wheezing or persistent asthma.
  • Using long-acting antimuscarinic antagonists (LAMAs) with inhaled corticosteroids for long-term asthma management. A LAMA is a bronchodilator, a medicine that helps to keep airway muscles relaxed.
  • Using allergy shots that contain very small amounts of allergen to treat some people with allergic asthma.
  • Using one or more methods to reduce exposure to indoor asthma triggers.
  • Using a fractional exhaled nitric oxide test to help manage asthma or help confirm a diagnosis in some patients when the diagnosis is unclear. This test involves breathing into a tube connected to a machine that measures the amount of nitric oxide, which can increase when there is airway inflammation.
  • Using bronchial thermoplasty to treat selected adults with persistent asthma. During this procedure heat is used to reduce the muscle around the airways.

“The new and updated recommendations help to better control asthma in children and adolescents through the use of existing medicines, allergy shots and control of environmental triggers,” says Dr. Teach. “Taken together, application of these guidelines will significantly improve care and outcomes for kids of all ages.”

Drs. Dewesh Agrawal, Andrew Dauber, Robert Freishtat, Vittorio Gallo

Four Children’s National Hospital leaders named to APS

Drs. Dewesh Agrawal, Andrew Dauber, Robert Freishtat, Vittorio Gallo

Drs. Dewesh Agrawal, Andrew Dauber, Robert Freishtat and Vittorio Gallo were named as 2021 American Pediatric Society members.

The American Pediatric Society (APS) has announced 55 new members, four of which are experts from Children’s National Hospital. Founded in 1888, the APS is the first and most prestigious academic pediatric organization in North America.

APS members are recognized child health leaders of extraordinary achievement who work together to shape the future of academic pediatrics. New members are nominated by current members through a process that recognizes individuals who have distinguished themselves as child health leaders, teachers, scholars, policymakers and/or clinicians.

“Our members represent the most distinguished and accomplished academic leaders in pediatrics whose outstanding work has advanced child health,” said APS President Steven Abman, M.D. “I am honored to welcome this exceptional group of individuals to the APS. The APS is especially looking forward to the active engagement of our membership with many exciting programs within the organization that are directed towards improvements in academic pediatric medicine, including more vigorous approaches to express our values of anti-racism, equity, diversity and inclusion.”

APS 2021 active new members from Children’s National are:

  • Dewesh Agrawal, M.D., vice-chair for Medical Education at Children’s National. Agrawal’s career has been marked by academic honors and teaching awards at every stage of his training and faculty employment. He has relentlessly devoted his energy to improving the educational experience for students, residents and fellows at Children’s National.
  • Andrew Dauber, M.D., M.M.Sc., chief of Endocrinology at Children’s National. Dr. Dauber’s leadership is reflected, nationally and internationally, in his ability to create research consortia, bringing together investigators to tackle complex questions. For example, he leads an NIH-funded consortium on the genetics of short statures, with multiple top children’s hospitals as partners. He also leads a large clinical trial testing a novel therapeutic agent for genetic short stature.
  • Robert Freishtat, M.D., M.P.H., senior investigator in the Center for Genetic Medicine of the Children’s National Research Institute (CNRI). Dr. Freishtat has authored or co-authored more than 100 articles and book chapters in the fields of pediatric lung injury, asthma, obesity, exosomes and emergency medicine. His research has been continuously funded by the NIH since 2003.
  • Vittorio Gallo, Ph.D., chief research officer at Children’s National and scientific director of CNRI. Dr. Gallo’s scientific success is attested to by over 130 peer-reviewed publications, many in very high-profile journals, as well as over 30 review articles and book chapters. He has received many national and international awards, including the NINDS Javits award in Neuroscience in 2018. Dr. Gallo has served on the editorial boards of many neuroscience journals, including Glia and the Annual Review in Neuroscience, and has been reviewing editor for the Journal of Neuroscience, all of which is a testament to the tremendous impact that his studies have had on the advancement of neurosciences.

“These new members represent multiple areas of Children’s National and have all leveraged the intersection of science, medicine and clinical education to make advances in their field of study,” said Stephen J. Teach, M.D., M.P.H., chair of the Department of Pediatrics at Children’s National. “Their work has, and will continue to, advance pediatric health care, and I congratulate them on their APS membership.”

little boy using asthma inhaler

Searching for the molecular underpinnings of asthma exacerbations

little boy using asthma inhaler

It’s long been known that colds, flu and other respiratory illnesses are major triggers for asthma exacerbations, says asthma expert Stephen J. Teach, M.D., MPH. Consequently, a significant body of research has focused on trying to figure out what’s happening on the cellular or molecular level as these illnesses progress to exacerbations.

People with asthma can be indistinguishable from people who don’t have this chronic airway disease – until they have an asthma attack, also known as an exacerbation. During these events, their airways become inflamed and swollen and produce an abundance of mucus, causing dangerous narrowing of the bronchial tubes that leads to coughing, wheezing and trouble breathing. These events are a major cause of morbidity and mortality, leading to the deaths of 10 U.S. residents every day, according to the Centers for Disease Control and Prevention.

It’s long been known that colds, flu and other respiratory illnesses are major triggers for asthma exacerbations, says Children’s National in Washington, D.C., asthma expert Stephen J. Teach, M.D., MPH. Consequently, a significant body of research has focused on trying to figure out what’s happening on the cellular or molecular level as these illnesses progress to exacerbations. Targeted searches have identified several different molecular pathways that appear to be key players in this phenomenon. However, Dr. Teach says researchers have been missing a complete and unbiased snapshot of all the important pathways in illness-triggered exacerbations and how they interrelate.

To develop this big picture view, Dr. Teach and  Inner-City Asthma Consortium colleagues recruited 208 children ages 6-17 years old with severe asthma – marked by the need for daily doses of inhaled corticosteroids, two hospitalizations or systemic corticosteroid treatments over the past year, and a high concentration of asthma-associated immune cells – from nine pediatric medical centers across the country, including Children’s National. (Inhaled corticosteroids are a class of medicine that calms inflamed airways.) The researchers collected samples of nasal secretions and blood from these patients at baseline, when all of them were healthy.

Then, they waited for these children to show symptoms of respiratory illnesses. Within six days of cold symptoms, the researchers took two more samples of nasal secretions and blood. They also administered breathing tests to determine whether these respiratory illnesses led to asthma exacerbations and recorded whether these patients were treated with systemic corticosteroids to stem the associated respiratory inflammation.

The researchers examined nasal fluid samples for evidence of viral infection during illness and used analytical methods to identify the causative virus. They analyzed all the samples they collected for changes in concentrations of various immune cells. They also looked globally in these samples for changes in gene expression compared with baseline and between the two collection periods during respiratory illness.

Together, this information told the molecular story about what took place after these children got sick and after some of them developed exacerbations. Of the 208 patients recruited, 106 got respiratory illnesses during the six-month study period, leading to a total of 154 illness events. Of those, 47 caused exacerbations, and 107 didn’t.

About half the exacerbations appeared to have been triggered by a rhinovirus, a cause of common colds, the research team reports in a study published online April 8, 2019, in Nature Immunology. The other children’s cold-like symptoms could have been triggered by pollution, allergens or other irritants.

In most exacerbations, virally triggered or not, the researchers saw early activation of a network of genes that appeared to be associated with SMAD3, a signaling molecule already known to be involved in airway inflammation. At the same time, genes that control a set of immune cells known as lymphocytes were turned down. However, as the exacerbation progressed and worsened, the researchers saw gene networks turned on that related to airway narrowing, mucus hypersecretion and activation of other immune cells.

Exacerbations triggered by viruses were associated with multiple inflammatory pathways, in contrast to those in which viruses weren’t found, which were associated with molecular pathways that affected cells in the airway lining.

The researchers validated these findings in 19 patients who each got respiratory illnesses at least twice during the study period but only developed an exacerbation during one of these episodes, finding the same upregulated and downregulated molecular pathways in these patients as in the study population as a whole. They also identified a set of molecular risk factors in patients at baseline – signatures of gene activation that appeared to put patients at risk for exacerbations when they got sick. When patients were treated with systemic corticosteroids during exacerbations, these medicines appeared to restore only some of the affected molecular pathways to normal, healthy levels. Other molecular pathways remained markedly changed.

Each finding could represent a new target for drugs that could prevent or more effectively treat exacerbations, keeping more patients with asthma healthy and out of the hospital.

“Our consortium study found increased gene expression of enzymes that produce molecules that contribute to narrowed airways and dilated blood vessels,” Dr. Teach adds. “This is especially intriguing because drugs that target kallikreins or bradykinin may help treat asthma attacks that aren’t caused by viruses.”

In addition to Dr. Teach, study co-authors include Lead Author Matthew C. Altman, University of Washington; Michelle A. Gill, Baomei Shao and Rebecca S. Gruchalla, all of University of Texas Southwestern Medical Center; Elizabeth Whalen and Scott Presnell of Benaroya Research Institute; Denise C. Babineau and Brett Jepson of Rho, Inc.; Andrew H. Liu, Children’s Hospital Colorado; George T. O’Connor, Boston University School of Medicine; Jacqueline A. Pongracic, Ann Robert H. Lurie Children’s Hospital of Chicago; Carolyn M. Kercsmar and Gurjit K. Khurana Hershey, , Cincinnati Children’s Hospital; Edward M. Zoratti and Christine C. Johnson, Henry Ford Health System; Meyer Kattan, Columbia University College of Physicians and Surgeons; Leonard B. Bacharier and Avraham Beigelman, Washington University, St. Louis; Steve M. Sigelman, Peter J. Gergen, Lisa M. Wheatley and Alkis Togias, National Institute of Allergy and Infectious Diseases; and James E. Gern, William W. Busse and Senior author Daniel J. Jackson, University of Wisconsin School of Medicine and Public Health.

Funding for research described in this post was provided by the National Institute of Allergy and Infectious Diseases under award numbers 1UM1AI114271 and UM2AI117870; CTSA under award numbers UL1TR000150, UL1TR001422 and 5UL1TR001425; the National Institutes of Health under award number UL1TR000451;  CTSI under award number 1UL1TR001430; CCTSI under award numbers UL1TR001082 and 5UM1AI114271; and NCATS under award numbers UL1 TR001876 and UL1TR002345.

Stephen Teach does an asthma exam

Stephen J. Teach, M.D., MPH, inaugural holder of new endowed chair

Stephen Teach does an asthma exam

Stephen J. Teach, M.D., M.P.H., has been named the inaugural Wendy Goldberg Professor in Translational Research in Child Health and Community Partnerships. This professorship comes with an endowed chair at Children’s National Health System.

The prestigious honor is given for the duration of Dr. Teach’s (and future chair holders’) employment at Children’s National. The award’s namesake, Wendy Goldberg, and her husband, Fred T. Goldberg Jr., are among the brightest stars in the constellation of Children’s National supporters, says Dr. Teach, Associate Dean for Pediatric Academic Affairs and Chair of the Department of Pediatrics at The George Washington University School of Medicine & Health Sciences.

In addition to serving on many Children’s boards, in the mid-2000s the Goldbergs made a $250,000 gift that benefited Improving Pediatric Asthma Care in the District of Columbia (IMPACT DC), Dr. Teach’s award-winning program to improve clinical care, empower patients and families, and conduct new research to improve patients’ outcomes.

“In recognition of the anchor aims of Children’s new strategic plan, the Goldbergs wanted this new gift to focus on the intersection of community health and research,” Dr. Teach says. “Thanks to their generosity, my team will work with community partners to use data to drive improvements in population health.”

With the dedicated funding Dr. Teach was able to hire a new staffer, Caitlin Munoz, to help mine electronic health records to create disease-specific registries that include 15,000 children and adolescents – the lion’s share of kids younger than 17 who live in Washington and have asthma.

“For the first time, we will be able to describe in granular detail the near-universe of local children who have this chronic respiratory disease,” he says. “We will be able to describe many of the most clinically meaningful aspects of nearly every child with asthma who lives in D.C., including mean age, gender, ethnicity and mean number visits to the emergency department.”

Such a richly textured database will help identify children who should be prescribed daily controller medications to help them avoid missing school days due to asthma exacerbations, he says. The next pediatric chronic disease they will track via registry will be pediatric obesity via elevated body mass index.

“That, in and of itself, is insightful data. But the enduring impact of this applied research is it will inform our continuous quality-improvement efforts,” he adds.

By querying the registries the team will be able to tell, for example, how Children’s primary care centers rank comparatively by asking such questions as which percentage of kids with asthma actually take the medicines they had been prescribed the year prior.

“Increasingly, clinical research falls into one of two buckets. You can either do better things: That’s discovering new drugs or processes, like our ongoing clinical trial to desensitize kids to asthma allergens. Or, you can do things better. We often know what to do already. We know that guideline-based asthma care works well. We don’t need to prove that again. We just need to do things better by getting this care to the kids who need it. That’s where this line of research/quality improvement comes in: It’s getting people to do things better.”

Stephen Teach

Stephen Teach, M.D., M.P.H., named associate dean at GW School of Medicine and Health Sciences

Stephen Teach

Stephen J. Teach, M.D., M.P.H., chair of the Department of Pediatrics at Children’s National Health System, was named associate dean for Pediatric Academic Affairs at The George Washington University (GW) School of Medicine and Health Sciences.

Dr. Teach is director and principal investigator of Improving Pediatric Asthma Care in the District of Columbia (IMPACT DC), a care, research and advocacy program focused on helping under-resourced and largely minority children who suffer from asthma. He also serves as principal investigator for the Washington site for the Inner City Asthma Consortium, funded by the National Institutes of Health.

At GW, Dr. Teach will play a critical role in supporting and enhancing education and training relationships between the university and Children’s National and will support the academic advancement of Children’s National faculty. Read more.

asthma medication delivery

School’s in for asthma medication adherence

asthma medication delivery

A research team from Children’s National tried to reduce missed doses of daily medications, improve asthma control and tamp down on schoolchildren’s asthma attacks by outsourcing morning delivery of inhaled corticosteroids to the school nurse.

Doctors and researchers have long known that the level of stress patients experience is inversely linked to how adherent they are with taking medications: The higher the stress, the less likely patients are to take doses of their medication correctly, on time or at all. For families of school-aged children, there are few times more stressful than mornings, when parents or caregivers need to get kids ready for their school day, pack everything they need and get them out the door on time.

These stressful mornings, says Stephen J. Teach, M.D., M.P.H., chair of the Department of Pediatrics at Children’s National Health System, can spell danger for children with persistent asthma. This chronic condition is typically treated with nightly and morning doses of inhaled corticosteroids (ICS), medications that decrease lung inflammation to prevent asthma attacks. When children miss a morning dose because their families are too busy, their asthma symptoms can exacerbate, causing them to miss school, be unable to participate in activities like sports or lose sleep at night.

But Dr. Teach and colleagues had a simple idea to bypass the morning struggle for many families: Instead of trying to fit delivery of ICS into an already packed schedule, why not outsource it to the school nurse?

“We thought that if we could have those morning doses administered by these medically trained individuals with great technique and regularity, then maybe we would see some improved outcomes in kids,” Dr. Teach says. “And we did, in a striking way.”

Dr. Teach and colleagues recruited 46 children to participate in a pilot study, published online June 8, 2017 in the Journal of Asthma. To be eligible, these participants had to be in grades kindergarten through eighth in the Washington, D.C. public school system and on Medicaid, demonstrating the type of financial need that can add to the cumulative stress a family already faces. The children were scattered across 18 schools.

“We thought that if we could have those morning doses administered by these medically trained individuals with great technique and regularity, then maybe we would see some improved outcomes in kids,” Dr. Teach says. “And we did, in a striking way.”

Twenty-one of these participants received morning doses of ICS (the intervention group), which the researchers provided to school nurses along with an asthma action plan. The rest (the control group) remained on their prescribed morning and evening doses at home.

After 60 days, the researchers followed up with schools and families. Through electronic records kept by each school, the researchers found that the intervention group received more than 90 percent of their prescribed morning doses—about the same number reported by parents of the control group. However, the two groups demonstrated impressive differences in quality-of-life measures:

  • While about 24 percent of the intervention group missed one or fewer days of school due to asthma during the 60-day trial, about 44 percent of the control group did.
  • About 43 percent of the intervention group reported functional limitations due to their asthma, compared with 74 percent of the control group.
  • The intervention group reported only 1.7 nights with asthma-related sleep loss in the previous two weeks, compared with 4.1 nights in the control group.
  • Additionally, only about one-quarter of the intervention group required adjustments in family life to accommodate their asthma, compared with more than one-half of the control group.

The reasons for these differences aren’t clear, says Dr. Teach. But he and colleagues suggest that they might be due to over-reporting of how many doses were delivered at home in the control group or improper administration of these drugs at home.

Regardless, he says, the results show that this type of school-based intervention was not only feasible for children, school nurses and families, but also led to numerous positive health outcomes for the participants who received it. Based on the results of this study, Dr. Teach and colleagues have started to prescribe school-based administration of morning ICS doses to families interested in receiving them as a new standard of care.

“These data, combined with data from similar studies at other institutions, suggest that school-based therapy is increasingly becoming a very real and proven option for clinicians and families when adherence is a struggle,” he says.

asthma inhailer

A successful patient-centered asthma study

A study by Stephen Teach, M.D., M.P.H., shows that extensively engaging stakeholders such as parents, families and local service providers in study design can transform a planned research project into a more patient-centered study.

For hundreds of years, scientific and medical research has followed a process that practically all grade-school children learn as the scientific method: Scientists make observations that lead to a question. After developing a hypothesis, the researchers and colleagues — usually other scientists in the same field — test it by gathering data from experiments, making more observations or searching through the existing literature. Once they have an answer, the researchers often publish it in a scientific journal, which can generate new questions among peer scientists and starts the cycle all over again.

While most research is meant to benefit humankind as a whole, non-scientists and people who aren’t research subjects usually aren’t involved much in the process itself. That can be a serious omission, particularly for medical research, says Stephen J. Teach, M.D., M.P.H., chair of the Department of Pediatrics at Children’s National Health System, and Deborah Quint Shelef, M.P.H., C.C.R.P., AE-C., program director at IMPACT DC, a program at Children’s National Health System that helps patients effectively manage asthma.

“Our patients might view research a little differently than we do. They don’t just want general contributions to knowledge, but specific contributions that people can actually use,” Shelef says. “One of our main goals is to have useful research models that can translate into changes that really improve patient care. It’s hard to make this happen without asking people who are affected most what would address their needs.”

That’s why Shelef and Dr. Teach’s most recent study, featured on the cover of the December 2016 issue of The Journal of Allergy and Clinical Immunology, shifts the research paradigm from a scientist-centered model to what they call a stakeholder-centered approach. Rather than develop the study solely with fellow researchers, the research team led by Children’s National relied heavily on guidance from people who would be most impacted by the results.

The study focused on whether an intervention that reduced parental stress could improve asthma outcomes among low-income African American children. To help design their study, the research team looked to several different sources for advice: African American parents of children treated for asthma at Children’s National; local providers of social, medical, legal and educational services; and experts in psychosocial stress, medication adherence and conducting studies among at-risk youth with asthma.

The researchers gave themselves one year to consult multiple times with each stakeholder group before starting to enroll study subjects in May 2015. In the initial planning phases, the research team intended to focus their study on whether reducing parental stress would change how well children stuck to taking their asthma medications. However, that focus quickly changed, says Shelef. “Medication adherence just wasn’t a meaningful goal to most parents,” she explains. “To them, having more symptom-free days was a better gauge of how well an intervention was working for their children.”

The proposed intervention itself also transformed. Rather than focusing on problem-solving, cognitive-reframing and parenting skills — the researchers’ initial ideas — the final intervention would instead teach participants mindfulness, deep breathing, positive thinking, self-care and gratitude — as well as how to use these coping skills with their children. Rather than being staffed by social workers or psychologists, the stakeholders preferred people they felt they could relate to: Community wellness coaches with experience teaching yoga, meditation or other wellness activities in neighborhoods in which they lived.

Several other tweaks significantly changed the study from its early incarnation into the final version that the researchers are currently implementing, says Dr. Teach. “We ended up in a very different place from where we started based on this extensive process of stakeholder engagement,” he says.

Shelef notes that it’s not always feasible to involve stakeholders so heavily or to intensively plan a study for a year before it begins. Keeping all the advisers focused on the study at hand without radically changing the focus was a challenge, she says, and it was an “incredible scramble” in the end to translate all of their feedback into a cohesive product. However, having input from the people who could gain the most from the research results made it all worth it.

“The real benefit to this approach is the richness of the final product,” Shelef says. “Ultimately, this study will show a lot more than if we hadn’t put so much into it at the beginning.”

Study reveals asthma phenotypes in inner-city children

xxoct16asthmaphenotypesrgimage

What’s known

According to the Centers for Disease Control and Prevention, 8.6 percent of children across the nation, or 6.3 million kids, have asthma, a disease characterized by wheezing and coughing associated with airway obstruction, bronchial hyperresponsiveness, and inflammation of the airway. However, children with asthma with low socioeconomic status who live in inner cities experience a disproportionately high burden of illness. While treatment guidelines provide uniformity in managing allergy and allergic inflammation, such approaches may be misdirected when kids have asthma symptoms but lack allergy or allergic inflammation. Knowledge of distinct disease phenotypes can help to improve care.

What’s new

The Asthma Phenotypes in the Inner City study enrolled school-aged kids living in nine U.S. inner cities, including Washington, DC. The research team collected data about their asthma at the beginning of the one-year study and every two months as the kids’ asthma was managed according to accepted guidelines. Phenotypic analysis for 616 of these kids found their asthma clustered into five distinct groups. Cluster “A” was characterized by lower allergy, lower inflammation, and minimal symptoms. Fifteen percent of the kids fit within “A.” Another 15 percent of kids’ asthma fit within Cluster “B.” They had highly symptomatic asthma despite high step-level treatment and relatively low allergy and inflammation. Cluster “C” was distinguished by minimal symptoms, intermediate allergy and inflammation, and mildly impaired pulmonary physiology. Some 24 percent of kids fit within this group. The remaining kids fit within Cluster “D” or “E” and experienced progressively higher asthma and rhinitis symptoms as well as allergy and inflammation.

Questions for future research

Q: How does exposure to allergens, viruses, and irritants like tobacco smoke—taken individually as well as in combination—influence asthma severity and symptoms for these at-risk youths?
Q: What approaches to treatment might result from these studies?

Training developing immune systems to prevent wheezing early in life

Stephen Teach does an asthma exam

Extensively engaging stakeholders such as parents, families and local service providers in the actual study design transformed a planned research project into a more patient-centered study.

For the small number of U.S. children who grow up on working farms, activities such as feeding the cows and clearing spent hay from the barn are little changed from a thousand years ago. Through such close contact with dirt and farm animals, rural kids’ immune systems develop more normally and better distinguish common bacteria from household allergens like dust, molds, pets, and pests. Rates of allergy and asthma continue to be lower in children who grow up in those conditions.

By contrast, rates of asthma have spiked among urban and disadvantaged kids, who have far less exposure to dirt and animals early in life. Today, leading pediatric institutions, such as Children’s National Health System, are “awash in emergency department (ED) visits for asthma” with each ED visit associated with 10 to 15 missed school days annually on a population basis, says Stephen J. Teach, MD, MPH, Director and Principal Investigator of IMPACT DC , a care, research, and advocacy program focused on under-resourced and largely minority children with asthma.

A paradigm-shifting multicenter clinical trial aims to reverse that trend by going old school and safely exposing very young infants to the type of immune system training they would have experienced if they grew up closer to the earth.

The five-year study, named “Oral Bacterial Extracts (ORBEX): Primary Prevention of Asthma and Wheezing in Children,” is funded by a $27 million cooperative agreement grant from the National Heart, Lung, and Blood Institute, which is part of the National Institutes of Health. Children’s National, one of eight participating sites across the nation, will enroll an estimated 150 children in the study and will receive at least $2.5 million of that grant.

“It is currently thought by many, including me, that asthma and allergic diseases are a result of disordered development of the immune system very early in life,” says Dr. Teach, who is also Chair of the Department of Pediatrics at George Washington University. The immune system development process begins to unfold in the last few months of pregnancy and continues through infancy, meaning “the die is cast, we think, at a very young age.”

According to the Centers for Disease Control and Prevention, 8.6 percent of children across the nation have asthma, but in the District of Columbia, a disproportionately higher number of children suffer from the respiratory ailment. Once children experience early wheezing, changes begin to occur in the architecture of their lungs, causing a thicker basement membrane, a thickening of the lining of the lungs, and resulting in a heightened tendency for the airways in the lungs to become inflamed and to excrete more mucous. As a result, the children’s poorly trained immune system becomes hyper vigilant, ready to recognize a multitude of things as potentially allergenic.

“We’ve got to do something to change the course of the disease and to make it less common and less severe,” Dr. Teach says.

The study will identify 1,000 babies who range in age from 6 months to 18 months who are the highest risk for asthma, either through family history, being diagnosed with eczema, or both. The infants will receive safe doses of the inactivated bacteria, which is marketed under the name Broncho-Vaxom®. The therapy comes in capsule form, which for two years will be sprinkled into bottles or onto food. The children will be followed to gauge whether infants randomly assigned to receive treatment suffer fewer respiratory symptoms than infants randomly assigned to receive placebo.

“The rationale if we can expose these very young children to the benefits, but not the risks, of early life bacterial exposure, they may reap the benefits of developing a more properly functioning and less allergic immune system,” Dr. Teach says.

He says the Children’s National research team has had “remarkable success” engaging young children and their parents in such long-term studies, losing few to attrition.

“Going for five years will be breaking new ground. But all of our experience suggests that we will succeed if we show the families we care, we stay in touch with them, and we form these therapeutic partnerships by saying: ‘We want to partner with you. We can do this safely with mutual benefit.’ Families will get on board,” he says.

Related resources: Learn more about the clinical trial | Research at a Glance