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Monoclonal antibody reduces asthma exacerbations in urban youth: Q&A with Stephen Teach, M.D.

August 12, 2022

Child using inhaler for asthma New research found that mepolizumab, a monoclonal antibody, decreased asthma flare-ups by 27% in Black and Hispanic children and adolescents who have a severe form of asthma, are prone to asthma attacks, and live in low-income urban neighborhoods.

Stephen Teach, M.D., principal investigator of the IMPACT DC asthma program and co-author of the NIAID-funded Inner City Asthma Consortium-conducted study, offers insight on the importance of this work and what it means for the future of pediatric asthma care at Children’s National Hospital.

What has been the hold-up in this field and how does this work move the field forward?

Urban, Black, and Hispanic children with asthma continue to suffer a disproportionate share of asthma-related morbidity. These findings show that innovative, phenotype-specific therapies are necessary to address their needs.

The study’s investigators were able to document a significant treatment effect in a particularly at-risk population and demonstrated specific gene pathways that were downregulated by treatment with mepolizumab.

What did you find that excites you about this work?

The exciting part of the Inner-City Asthma Consortium’s work has always been that it not only studies whether or not phenotype-driven interventions improve outcomes in high-risk kids, but how those interventions work from a fundamental mechanistic perspective. Those insights drive the science, and the potential clinical applications, forward in an iterative fashion.

How is Children’s National leading in this space?

Investigators from Children’s National continue to be national leaders in developing and testing innovative interventions to address the national disparities in pediatric asthma care and outcomes.

The study, published in the journal The Lancet was co-authored by William Sheehan, M.D., allergist.

The Division of Pulmonary Medicine at Children’s National has been ranked as one of the top ten programs in the nation by U.S. News & World Report.

Autistic youth self-reporting critical to understanding of executive function challenges

July 9, 2021

Young people with autism are distinctly aware of their own challenges in areas such as flexibility, working memory and inhibition—abilities known collectively as “executive function,” according to the first study to measure and compare self-reports in these areas to more traditional reporting from parents.

Young people with autism are distinctly aware of their own challenges in areas such as flexibility, working memory and inhibition — abilities known collectively as “executive function,” according to the first study to measure and compare self-reports in these areas to more traditional reporting from parents. The study appears in the Journal Autism.

While autism research has started to focus on incorporating the experiences of autistic people themselves through self-reporting and greater inclusion in the design and execution of related research, this is the first time that a study has definitively captured self-reports of executive functions directly from young people with autism.

The study, which included 197 autistic youth, found that while both youth and their parents are in basic agreement about which areas of executive functioning that individual youth struggle with most, parents tended to report higher levels of impairment than the youth reported themselves. Executive function is related to a person’s ability to complete tasks such as adjusting to change, making a plan, getting organized and following through, as well as basic daily tasks like getting up and getting dressed or making small talk.

“While parents are reporting on outwardly observed behaviors in the context of home/community, for example, youth are reporting on their inner experiences across many contexts,” said Lauren Kenworthy, Ph.D., first author on the study and director of the Center for Autism Spectrum Disorders at Children’s National Hospital. “Our findings support the idea that autistic youth may be drawing their conclusions from different environmental data and cognitive frameworks than their parents, which adds a new dimension to our understanding of executive function in people with autism.”

The data are especially compelling because youth and parent reports of executive function were gathered on parallel measures with consistent items and factor structure, allowing for a true one-to-one comparison between youth and parent reporting.

“These kids are very aware of the areas where they struggle,” Dr. Kenworthy said. “And the findings from this study further elevate the importance of making sure that assessments of executive function take into account the perspective of the youth themselves, which can provide powerful insights into the interventions that they may benefit from the most.”

The study also compared reports from autistic youth to reports from both neurotypical youth and those with attention deficit hyperactivity disorder (ADHD), another condition where executive functioning skills can be challenged. There were distinct differences between all three groups—and the challenges profiled by youth with autism and those with ADHD were distinct from each other. For example, autistic youth reported greater challenges with flexibility, emotional control and self-monitoring than those with ADHD, who reported greater struggles with working memory.

The authors noted that future studies should include more performance-based measures, as well as larger numbers of females and people with intellectual disabilities to better understand how self-reporting can play a role in understanding and helping these specific groups. Additionally, developing new measures that capture the inner experience of autism by engaging autistic people in their creation could provide deeper insight into how young people with autism experience the world and how interventions designed to assist them are working (or not).

“These data provide clear evidence of the executive functioning challenges actually experienced by autistic youth as well as the primary role inflexibility plays in the lives of these young people,” the authors concluded. “This additional perspective and context for the experiences of these executive functioning challenges are of high clinical value and complement more frequently gathered assessments in ways never captured before.”

Research and Education Week honors innovative science

April 19, 2019

Billie Lou Short, M.D., received the Ninth Annual Mentorship Award in Clinical Science.

People joke that Billie Lou Short, M.D., chief of Children’s Division of Neonatology, invented extracorporeal membrane oxygenation, known as ECMO for short. While Dr. Short did not invent ECMO, under her leadership Children’s National was the first pediatric hospital to use it. And over decades Children’s staff have perfected its use to save the lives of tiny, vulnerable newborns by temporarily taking over for their struggling hearts and lungs. For two consecutive years, Children’s neonatal intensive care unit has been named the nation’s No. 1 for newborns by U.S. News & World Report. “Despite all of these accomplishments, Dr. Short’s best legacy is what she has done as a mentor to countless trainees, nurses and faculty she’s touched during their careers. She touches every type of clinical staff member who has come through our neonatal intensive care unit,” says An Massaro, M.D., director of residency research.

For these achievements, Dr. Short received the Ninth Annual Mentorship Award in Clinical Science.

Anna Penn, M.D., Ph.D., has provided new insights into the central role that the placental hormone allopregnanolone plays in orderly fetal brain development, and her research team has created novel experimental models that mimic some of the brain injuries often seen in very preterm babies – an essential step that informs future neuroprotective strategies. Dr. Penn, a clinical neonatologist and developmental neuroscientist, “has been a primary adviser for 40 mentees throughout their careers and embodies Children’s core values of Compassion, Commitment and Connection,” says Claire-Marie Vacher, Ph.D.

For these achievements, Dr. Penn was selected to receive the Ninth Annual Mentorship Award in Basic and Translational Science.

The mentorship awards for Drs. Short and Penn were among dozens of honors given in conjunction with “Frontiers in Innovation,” the Ninth Annual Research and Education Week (REW) at Children’s National. In addition to seven keynote lectures, more than 350 posters were submitted from researchers – from high-school students to full-time faculty – about basic and translational science, clinical research, community-based research, education, training and quality improvement; five poster presenters were showcased via Facebook Live events hosted by Children’s Hospital Foundation.

Two faculty members won twice: Vicki Freedenberg, Ph.D., APRN, for research about mindfulness-based stress reduction and Adeline (Wei Li) Koay, MBBS, MSc, for research related to HIV. So many women at every stage of their research careers took to the stage to accept honors that Naomi L.C. Luban, M.D., Vice Chair of Academic Affairs, quipped that “this day is power to women.”

Here are the 2019 REW award winners:

2019 Elda Y. Arce Teaching Scholars Award
Barbara Jantausch, M.D.
Lowell Frank, M.D.

Suzanne Feetham, Ph.D., FAA, Nursing Research Support Award
Vicki Freedenberg, Ph.D., APRN, for “Psychosocial and biological effects of mindfulness-based stress reduction intervention in adolescents with CHD/CIEDs: a randomized control trial”
Renee’ Roberts Turner for “Peak and nadir experiences of mid-level nurse leaders”

2019-2020 Global Health Initiative Exploration in Global Health Awards
Nathalie Quion, M.D., for “Latino youth and families need assessment,” conducted in Washington
Sonia Voleti for “Handheld ultrasound machine task shifting,” conducted in Micronesia
Tania Ahluwalia, M.D., for “Simulation curriculum for emergency medicine,” conducted in India
Yvonne Yui for “Designated resuscitation teams in NICUs,” conducted in Ghana
Xiaoyan Song, Ph.D., MBBS, MSc, “Prevention of hospital-onset infections in PICUs,” conducted in China

Ninth Annual Research and Education Week Poster Session Awards

Basic and Translational Science
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Differences in the gut microbiome of HIV-infected versus HIV-exposed, uninfected infants”
Faculty: Hayk Barseghyan, Ph.D., for “Composite de novo Armenian human genome assembly and haplotyping via optical mapping and ultra-long read sequencing”
Staff: Damon K. McCullough, BS, for “Brain slicer: 3D-printed tissue processing tool for pediatric neuroscience research”
Staff: Antonio R. Porras, Ph.D., for “Integrated deep-learning method for genetic syndrome screening using facial photographs”
Post docs/fellows/residents: Lung Lau, M.D., for “A novel, sprayable and bio-absorbable sealant for wound dressings”
Post docs/fellows/residents: Kelsey F. Sugrue, Ph.D., for “HECTD1 is required for growth of the myocardium secondary to placental insufficiency”
Graduate students: Erin R. Bonner, BA, for “Comprehensive mutation profiling of pediatric diffuse midline gliomas using liquid biopsy”
High school/undergraduate students: Ali Sarhan for “Parental somato-gonadal mosaic genetic variants are a source of recurrent risk for de novo disorders and parental health concerns: a systematic review of the literature and meta-analysis”

Clinical Research
Faculty: Amy Hont, M.D., for “Ex vivo expanded multi-tumor antigen specific T-cells for the treatment of solid tumors”
Faculty: Lauren McLaughlin, M.D., for “EBV/LMP-specific T-cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation”

Staff: Iman A. Abdikarim, BA, for “Timing of allergenic food introduction among African American and Caucasian children with food allergy in the FORWARD study”
Staff: Gelina M. Sani, BS, for “Quantifying hematopoietic stem cells towards in utero gene therapy for treatment of sickle cell disease in fetal cord blood”
Post docs/fellows/residents: Amy H. Jones, M.D., for “To trach or not trach: exploration of parental conflict, regret and impacts on quality of life in tracheostomy decision-making”
Graduate students: Alyssa Dewyer, BS, for “Telemedicine support of cardiac care in Northern Uganda: leveraging hand-held echocardiography and task-shifting”
Graduate students: Natalie Pudalov, BA, “Cortical thickness asymmetries in MRI-abnormal pediatric epilepsy patients: a potential metric for surgery outcome”
High school/undergraduate students: Kia Yoshinaga for “Time to rhythm detection during pediatric cardiac arrest in a pediatric emergency department”

Community-Based Research
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Recent trends in the prevention of mother-to-child transmission (PMTCT) of HIV in the Washington, D.C., metropolitan area”
Staff: Gia M. Badolato, MPH, for “STI screening in an urban ED based on chief complaint”
Post docs/fellows/residents: Christina P. Ho, M.D., for “Pediatric urinary tract infection resistance patterns in the Washington, D.C., metropolitan area”
Graduate students: Noushine Sadeghi, BS, “Racial/ethnic disparities in receipt of sexual health services among adolescent females”

Education, Training and Program Development
Faculty: Cara Lichtenstein, M.D., MPH, for “Using a community bus trip to increase knowledge of health disparities”
Staff: Iana Y. Clarence, MPH, for “TEACHing residents to address child poverty: an innovative multimodal curriculum”
Post docs/fellows/residents: Johanna Kaufman, M.D., for “Inpatient consultation in pediatrics: a learning tool to improve communication”
High school/undergraduate students: Brett E. Pearson for “Analysis of unanticipated problems in CNMC human subjects research studies and implications for process improvement”

Quality and Performance Improvement
Faculty: Vicki Freedenberg, Ph.D., APRN, for “Implementing a mindfulness-based stress reduction curriculum in a congenital heart disease program”
Staff: Caleb Griffith, MPH, for “Assessing the sustainability of point-of-care HIV screening of adolescents in pediatric emergency departments”
Post docs/fellows/residents: Rebecca S. Zee, M.D., Ph.D., for “Implementation of the Accelerated Care of Torsion (ACT) pathway: a quality improvement initiative for testicular torsion”
Graduate students: Alysia Wiener, BS, for “Latency period in image-guided needle bone biopsy in children: a single center experience”

View images from the REW2019 award ceremony.

Therapeutic targets in African-American youth with type 2 diabetes

October 4, 2018

boy on a treadmil

Ongoing research is helping to define the broad spectrum and multi-faceted nature of type 2 diabetes in terms of its presentation, its rapidity of progression and its underlying genetic susceptibilities. In a recent study of 8,980 adults published in The Lancet, diabetes was further classified into five clusters, ranging from insulin-deficient, typically referred to as type 1, to groups of patients with primary insulin-resistance, traditionally classified as type 2 diabetes, with the caveat that each cluster had a distinct risk profile for disease progression and risk for diabetes complications.

Moreover, investigators have recently demonstrated, through the Restoring Insulin Secretion (RISE) Consortium, that youth compared to adults with early type 2 diabetes have greater insulin resistance relative to insulin secretion. Understanding variances on the diabetes spectrum, especially as it relates to risk for disease progression in youth, helps researchers develop targeted therapies that may help reduce complications and the burden of this chronic disease.

Ongoing research

Stephanie Chung, M.B.B.S., a pediatric endocrinologist at the National Institutes of Health and an adjunct assistant professor of pediatrics at Children’s National, is one researcher who hopes to use this knowledge to transform public health outcomes. Dr. Chung is studying how teens and young adults with severe insulin-resistant diabetes (SIRD) respond to new treatment, paired with lifestyle-based interventions.

Here is a Q&A with Dr. Chung about her latest research:

Tell Innovation District readers more about your diabetes research. How has your previous research influenced this study?

My research and publications are focused on understanding how genes, environment and lifestyle factors contribute to the pathology of diabetes, obesity and insulin resistance in populations of African descent and on identifying more effective screening and treatment options.

We know that African-American youth with type 2 diabetes have the highest complication and treatment failure rates among minority youth. However, the reasons underlying this health disparity are still not fully understood. Metformin, the only approved oral diabetes treatment for youth with type 2 diabetes, works less than half of the time in African-American youth. Although new evidence suggests that gut bacteria and genetics may influence the efficacy of metformin, this data is insufficient in African-American youth.

What is your goal with this diabetes clinical study?

The primary objective of this new study, entitled Therapeutic Targets in African-American Youth with Type 2 Diabetes, is to compare the combination of metformin and liraglutide versus metformin alone to reduce excess glucose produced by the liver in African-American youth with type 2 diabetes.

Additional objectives will evaluate the mechanism of action in the liver of these two agents and the influence of genetics and gut bacteria. This project brings together the research expertise of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Human Genome Research Institute and the Children’s National.

Do you envision this type of dual therapy, a combination of drugs and lifestyle interventions, will serve as a bridge to optimal insulin function?

While metformin, diet and lifestyle changes remain the mainstay of diabetes treatment, our study will evaluate whether this combination regimen could help to slow the progression of type 2 diabetes in African American youth. Our ultimate goal is the development of new precision medicine treatment options that can address the disparities in outcomes for African-American youth with type 2 diabetes.

What lessons do you see participants learning as they progress through the trial?

Our patients and their families are equal partners in care. Our comprehensive team of doctors, nurses, dietitians and counselors work closely with the patients and their families to help empower them to take charge of managing their diabetes. We teach them skills that include regularly monitoring their blood glucose levels and understanding how their activity and foods affect these levels. They are coached on making healthy food choices and incorporating exercise into their daily lives.

How do you teach children and teens about how their body responds to different foods?

This education starts as soon as participants enter the study. While patients are at the NIH for the inpatient study, we provide them with meals containing different ratios of carbohydrates, proteins, and fats and help them to analyze how their blood sugar responds to these levels, both before and after they take the medication. This type of education is important since participants will also have to monitor their blood sugar twice a day at home during the study. Most of the time, we use real-life situations as teaching moments. For example, if a participant had pizza for dinner, we will discuss with them why their blood sugar spiked and suggest alternative food choices. We provide this type of coaching every week. I often joke that after three months they become tired of hearing from us. But one of the strengths of this study is that participants receive personalized feedback that enables them to make healthy food choices for the rest of their life.

Can you tell us more about targeted food choices for teens?

A very enlightening procedure that we conduct on all of our study participants is measuring their basal metabolic rate (energy expenditure at rest). We show them how many calories they need to consume each day to maintain their body’s normal functions and compare that number with an estimate of how many calories they usually consume in a day. For many participants this is the first time that they have insight into the reasons for their weight gain.

How does this lab work help with meal planning?

After we create a participant’s metabolic chart we make food plans that support their lifestyle and caloric needs and are realistic to follow. For example, a 2,000 calorie per day diet can be separated into 400 calories for breakfast, 600 calories for lunch, 200 calories for snack and 800 calories for dinner.

How do you envision personalizing the field of diabetes research and treatment?

A precision medicine approach to type 2 diabetes will help us to better explore if and how factors like genes, environment and lifestyle impact insulin and glucose metabolism in populations with significant treatment outcomes disparities. With this approach we hope to uncover novel targeted treatment and prevention strategies that demonstrate more efficacy and cost-efficiency than current treatment approaches for high-risk populations.

Where can people learn more about the trial?

Learn more about the study by watching this informational video. If you’re interested in joining the study, please contact the NIH Office of Clinical Trial Recruitment at 866-999-1116.