Mihailo Kaplarevic

Extracting actionable research data faster, with fewer hassles

Mihailo Kaplarevic

Mihailo Kaplarevic, Ph.D., the newly minted Chief Research Information Officer at Children’s National Hospital and Bioinformatics Division Chief at Children’s National Research Institute, will provide computational support, advice, informational guidance, expertise in big data and data analyses for researchers and clinicians.

Kaplarevic’s new job is much like the role he played most recently at the National Heart, Lung and Blood Institute (NHLBI), assembling a team of researchers and scientists skilled in computing and statistical analyses to assist as in-house experts for other researchers and scientists.

NHLBI was the first institute within the National Institutes of Health (NIH) family to set up a scientific information office. During his tenure, a half-dozen other NIH institutions followed, setting up the same entity to help bridge the enormous gap between basic and clinical science and everything related to IT.

“There is a difference compared with traditional IT support at Children’s National – which will remain in place and still do the same sort of things they have been doing so far,” he says of The Bear Institute for Health Innovation. “The difference is this office has experience in research because every single one of us was a researcher at a certain point in our career: We are published. We applied for grants. We lived the life of a typical scientist. On top of that, we’re coming from the computational world. That helps us bridge the gaps between research and clinical worlds and IT.”

Ultimately, he aims to foster groundbreaking science by recognizing the potential to enhance research projects by bringing expertise acquired over his career and powerful computing tools to help teams achieve their goals in a less expensive and more efficient way.

“I have lived the life of a typical scientist. I know exactly how painful and frustrating it can be to want to do something quickly and efficiently but be slowed by technological barriers,” he adds.

As just one example, his office will design the high-performance computing cluster for the hospital to help teams extract more useful clinical and research data with fewer headaches.

Right now, the hospital has three independent clinical systems storing patient data; all serve a different purpose. (And there are also a couple of research information systems, also used for different purposes.) Since databases are his expertise, he will be involved in consolidating data resources, finding the best way to infuse the project with the bigger-picture mission – especially for translational science – and creating meaningful, actionable reports.

“It’s not only about running fewer queries,” he explains. “One needs to know how to design the right question. One needs to know how to design that question in a way that the systems could understand. And, once you get the data back, it’s a big set of things that you need to further filter and carefully shape. Only then will you get the essence that has clinical or scientific value. It’s a long process.”

As he was introduced during a Children’s National Research Institute faculty meeting in late-September 2019, Kaplarevic joked that his move away from pure computer science into a health care and clinical research domain was triggered by his parents: “When my mom would introduce me, she would say ‘My son is a doctor, but not the kind of doctor who helps other people.’ ”

Some of that know-how will play out by applying tools and methodology to analyze big data to pluck out the wheat (useful data) from the chaff in an efficient and useful way. On projects that involve leveraging cloud computing for storing massive amounts of data, it could entail analyzing the data wisely to reduce its size when it comes back from the cloud – when the real storage costs come in. “You can save a lot of money by being smart about how you analyze data,” he says.

While he expects his first few months will be spent getting the lay of the land, understanding research project portfolios, key principal investigators and the pediatric hospital’s biggest users in the computational domain, he has ambitious longer-term goals.

“Three years from now, I would like this institution to say that the researchers are feeling confident that their research is not affected by limitations related to computer science in general. I would like this place to become a very attractive environment for up-and-coming researchers as well as for established researchers because we are offering cutting-edge technological efficiencies; we are following the trends; we are a secure place; and we foster science in the best possible way by making computational services accessible, affordable and reliable.”

Lee Beers

Getting to know Lee Beers, M.D., FAAP, future president-elect of AAP

Lee Beers

Lee Savio Beers, M.D., FAAP, Medical Director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital carved out a Monday morning in late-September 2019, as she knew the American Academy of Pediatrics (AAP) would announce the results of its presidential election, first by telephone call, then by an email to all of its members.  Her husband blocked off the morning as well to wait with her for the results.  She soon got the call that she was elected by her peers to become AAP president-elect, beginning Jan. 1, 2020. Dr. Beers will then serve as AAP president in 2021 for a one-year term.

That day swept by in a rush, and then the next day she was back in clinic, caring for her patients, some of them teenagers whom she had taken care of since birth. Seeing children and families she had known for such a long time, some of whom had complex medical needs, was a perfect reminder of what originally motivated Dr. Beers to be considered as a candidate in the election.

“When we all work together – with our colleagues, other professionals, communities and families – we can make a real difference in the lives of children.  So many people have reached out to share their congratulations, and offer their support or help. There is a real sense of collaboration and commitment to child health,” Dr. Beers says.

That sense of excitement ripples through Children’s National.

“Dr. Beers has devoted her career to helping children. She has developed a national advocacy platform for children. I can think of no better selection for the president-elect role of the AAP. She will be of tremendous service to children within AAP national leadership,” says Kurt Newman, M.D., Children’s National Hospital President and CEO.

AAP comprises 67​,000 pediatricians, and its mission is to promote and safeguard the health and well-being of all children – from infancy to adulthood.

The daughter of a nuclear engineer and a schoolteacher, Dr. Beers knew by age 5 that she would become a doctor. Trained as a chemist, she entered the Emory University School of Medicine after graduation. After completing residency at the Naval Medical Center, she became the only pediatrician assigned to the Guantanamo Bay Naval Station.

That assignment to Cuba, occurring so early in her career, turned out to be a defining moment that shapes how she partners with families and other members of the team to provide comprehensive care.

“I was a brand-new physician, straight out of residency, and was the only pediatrician there so I was responsible for the health of all of the kids on the base. I didn’t know it would be this way at the time, but it was formative. It taught me to take a comprehensive public health approach to taking care of kids and their families,” she recalls.

On the isolated base, where she also ran the immunization clinic and the nursery, she quickly learned she had to judiciously use resources and work together as a team.

“It meant that I had to learn how to lead a multi-disciplinary team and think about how our health care systems support or get in the way of good care,” she says.

One common thread that unites her past and present is helping families build resiliency to shrug off adversity and stress.

“The base was a difficult and isolated place for some families and individuals, so I thought a lot about how to support them. One way is finding strong relationships where you are, which was important for patients and families miles away from their support systems. Another way is to find things you could do that were meaningful to you.”

Cuba sits where the Atlantic Ocean, Caribbean Sea and Gulf of Mexico meet. Dr. Beers learned how to scuba dive there – something she never would have done otherwise – finding it restful and restorative to appreciate the underwater beauty.

“I do think these lessons about resilience are universal. There are actually a lot of similarities between the families I take care of now, many of whom are in socioeconomically vulnerable situations, and military families when you think about the level of stress they are exposed to,” she adds.

Back stateside in 2001, Dr. Beers worked as a staff pediatrician at the National Naval Medical Center in Bethesda, Maryland, and Walter Reed Army Medical Center in Washington, D.C. In 2003, Dr. Beers joined Children’s National Hospital as a general pediatrician in the Goldberg Center for Community Pediatric Health. Currently, she oversees the DC Collaborative for Mental Health in Pediatric Primary Care, a public-private coalition that elevates the standards of mental health care for all children, and is Co-Director of the Early Childhood Innovation Network. She received the Academic Pediatric Association’s 2019 Public Policy and Advocacy Award.

As a candidate, Dr. Beers pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns
  • Tackling physician burnout by supporting pediatricians through office-based education and systems reforms
  • Expanding community-based prevention and treatment

“I am humbled and honored to have the support of my peers in taking on this newest leadership role,” says Dr. Beers. “AAP has been a part of my life since I first became a pediatrician, and my many leadership roles in the DC chapter and national AAP have given me a glimpse of the collective good that pediatricians can accomplish by working together toward common strategic goals.”

AAP isn’t just an integral part of her life, it’s where she met her future husband, Nathaniel Beers, M.D., MPA, FAAP, President of The HSC Health Care System. The couple’s children regularly attended AAP meetings with them when they were young.

Just take a glimpse at Lee Beers’ Twitter news feed. There’s a steady stream of images of her jogging before AAP meetings to amazing sunrises, jogging after AAP meetings to stellar sunsets and always, always, images of the entire family, once collectively costumed as The Incredibles.

“I really do believe that we have to set an example: If we are talking about supporting children and families in our work, we have to set that example in our own lives. That looks different for everyone, but as pediatricians and health professionals, we can model prioritizing our families while still being committed to our work,” she explains.

“Being together in the midst of the craziness is just part of what we do as a family. We travel a lot, and our kids have gone with us to AAP meetings since they were infants. My husband even brought our infant son to a meeting at the mayor’s office when he was on paternity leave. Recognizing that not everyone is in a position to be able to do things like that, it’s important for us to do it – to continue to change the conversation and make it normal to have your family to be part of your whole life, not have a separate work life and a separate family life.”

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.

Children’s National ranked No. 6 overall and No. 1 for newborn care by U.S. News

Children’s National in Washington, D.C., is the nation’s No. 6 children’s hospital and, for the third year in a row, its neonatology program is No.1 among all children’s hospitals providing newborn intensive care, according to the U.S. News Best Children’s Hospitals annual rankings for 2019-20.

This is also the third year in a row that Children’s National has been in the top 10 of these national rankings. It is the ninth straight year it has ranked in all 10 specialty services, with five specialty service areas ranked among the top 10.

“I’m proud that our rankings continue to cement our standing as among the best children’s hospitals in the nation,” says Kurt Newman, M.D., President and CEO for Children’s National. “In addition to these service lines, today’s recognition honors countless specialists and support staff who provide unparalleled, multidisciplinary patient care. Quality care is a function of every team member performing their role well, so I credit every member of the Children’s National team for this continued high performance.”

The annual rankings recognize the nation’s top 50 pediatric facilities based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

“The top 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver outstanding care across a range of specialties and deserve to be nationally recognized,” says Ben Harder, chief of health analysis at U.S. News. “According to our analysis, these Honor Roll hospitals provide state-of-the-art medical expertise to children with rare or complex conditions. Their rankings reflect U.S. News’ assessment of their commitment to providing high-quality, compassionate care to young patients and their families day in and day out.”

The bulk of the score for each specialty is based on quality and outcomes data. The process also includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with challenging conditions.

Below are links to the five specialty services that U.S. News ranked in the top 10 nationally:

The other five specialties ranked among the top 50 were cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastro-intestinal surgery, orthopedics, and urology.

Gustavo Nino

Gustavo Nino, M.D., honored with national award from American Thoracic Society

Gustavo Nino

Gustavo Nino, M.D., a pulmonologist who directs the Sleep Medicine program at Children’s National, was honored by the American Thoracic Society with The Robert B. Mellins, M.D. Outstanding Achievement Award in recognition of his contributions to pediatric pulmonology and sleep medicine.

“I am humbled and pleased to be recognized with this distinction,” says Dr. Nino. “This national award is particularly special because it honors both academic achievements as well as research that I have published to advance the fields of pediatric pulmonology and sleep medicine.”

After completing a mentored career development award (K Award) from the National Institutes of Health (NIH), Dr. Nino established an independent research program at Children’s National funded by three different NIH R-level grants, an R01 research project grant; an R21 award for new, exploratory research; and an R4 small business/technology transfer award to stimulate research innovation.

The research team Dr. Nino leads has made important contributions to developing novel models to study the molecular mechanisms of airway epithelial immunity in newborns and infants. He also has pioneered the use of computer-based lung imaging tools and physiological biomarkers to predict early-life respiratory disease in newborns and infants.

Dr. Nino has published roughly 60 peer-review manuscripts including in the “Journal of Allergy and Clinical Immunology,” the “European Respiratory Journal,” and the “American Journal of Respiratory and Critical Care Medicine,” the three top journals in the field of respiratory medicine. He has been invited to chair sessions about sleep medicine during meetings held by the Pediatric Academic Societies, American College of Chest Physicians and the American Thoracic Society (ATS).

Dr. Nino also has served as NIH scientific grant reviewer of the Lung Cellular and Molecular Immunology Section; The Infectious, Reproductive, Asthma and Pulmonary Conditions Section; and The Impact of Initial Influenza Exposure on Immunity in Infants NIH/National Institute of Allergy and Infectious Diseases Special Emphasis Panel.

In addition to his research and academic contributions, over the past five years Dr. Nino has led important clinical and educational activities at Children’s National and currently directs the hospital’s Sleep Medicine program, which has grown to become one of the region’s largest programs conducting more than 1,700 sleep studies annually.

He has developed several clinical multidisciplinary programs including a pediatric narcolepsy clinic and the Advanced Sleep Apnea Program in collaboration with the Division of Ear, Nose and Throat at Children’s National. In addition, Dr. Nino started a fellowship program in Pediatric Sleep Medicine accredited by the Accreditation Council for Graduate Medical Education in collaboration with The George Washington University and has served as clinical and research mentor of several medical students, pediatric residents and fellows.

asthma inhailer

Picture imperfect: Eliminating asthma triggers through smartphones

asthma inhailer

Children’s National is among five awardees sharing $10 million in funding under Fannie Mae’s Sustainable Communities Innovation Challenge: Healthy Affordable Housing, a national competition to identify innovative ideas to help children and families enjoy safer homes. Fannie Mae made the funding announcement on May 21, 2019.

Children’s funding will underwrite a pilot program to use smartphones to enable virtual home visits, leveraging the skills of Children’s pediatric asthma specialists, health educators and community housing remediation specialists who will video conference with families in the home to identify potential housing asthma triggers.

According to the Centers for Disease Control and Prevention, 1 in 12 children and adolescents (6 million) have asthma, and one in six children with asthma visit the emergency department each year. In Washington, D.C., substandard housing can play an outsized role in triggering asthma exacerbations. Asthma-related hospital visits are 12 times higher in the city’s poorest neighborhoods, compared with affluent ZIP codes.

Working with community partners, Children’s faculty aim to eliminate asthma triggers right at the source, improving children’s well-being and creating healthier homes.

Right now during in-home visits, staff look for holes under kitchen sinks and gaps in the walls or flooring where pests and vermin might enter as well as leaks where mold and mildew can bloom. These systematic visits yield detailed notes to best direct resources to remediate those housing woes. The in-person visits however, are labor intensive and require delicate diplomacy to first open doors then to point out potential asthma triggers without coming off as judgmental.

“The beauty of our innovation is that residents can show us these same problematic locations using their smartphones, facilitating our efforts to target resources for that household. It’s a win for Children’s families because eliminating asthma triggers in the home means our kids will miss fewer school days, improving their lives and overall health,” says Ankoor Y. Shah, M.D., MBA, MPH, medical director for Children’s IMPACT DC Asthma Clinic.

Children’s collaborative project includes a number of partners, including:

Dr. Shah says the project will start in July 2019 with the pilot of virtual home visits starting in early 2020. This proof-of-concept model will hopefully be able to be replicated in other cities across the country.

Billie Lou Short and Kurt Newman at Research and Education Week

Research and Education Week honors innovative science

Billie Lou Short and Kurt Newman at Research and Education Week

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.

Beth Tarini

Getting to know SPR’s future President, Beth Tarini, M.D., MS

Beth Tarini

Quick. Name four pillar pediatric organizations on the vanguard of advancing pediatric research.

Most researchers and clinicians can rattle off the names of the Academic Pediatric Association, the American Academy of Pediatrics and the American Pediatric Society. But that fourth one, the Society for Pediatric Research (SPR), is a little trickier. While many know SPR, a lot of research-clinicians simply do not.

Over the next few years, Beth A. Tarini, M.D., MS, will make it her personal mission to ensure that more pediatric researchers get to know SPR and are so excited about the organization that they become active members. In May 2019 Dr. Tarini becomes Vice President of the society that aims to stitch together an international network of interdisciplinary researchers to improve kids’ health. Four-year SPR leadership terms begin with Vice President before transitioning to President-Elect, President and Past-President, each for one year.

Dr. Tarini says she looks forward to working with other SPR leaders to find ways to build more productive, collaborative professional networks among faculty, especially emerging junior faculty. “Facilitating ways to network for research and professional reasons across pediatric research is vital – albeit easier said than done. I have been told I’m a connector, so I hope to leverage that skill in this new role,” says Dr. Tarini, associate director for Children’s Center for Translational Research.

“I’m delighted that Dr. Tarini was elected to this leadership position, and I am impressed by her vision of improving SPR’s outreach efforts,” says Mark Batshaw, M.D., Executive Vice President, Chief Academic Officer and Physician-in-Chief at Children’s National. “Her goal of engaging potential members in networking through a variety of ways – face-to-face as well as leveraging digital platforms like Twitter, Facebook and LinkedIn – and her focus on engaging junior faculty will help strengthen SPR membership in the near term and long term.”

Dr. Tarini adds: “Success to me would be leaving after four years with more faculty – especially junior faculty – approaching membership in SPR with the knowledge and enthusiasm that they bring to membership in other pediatric societies.”

SPR requires that its members not simply conduct research, but move the needle in their chosen discipline. In her research, Dr. Tarini has focused on ensuring that population-based newborn screening programs function efficiently and effectively with fewer hiccups at any place along the process.

Thanks to a heel stick to draw blood, an oxygen measurement, and a hearing test, U.S. babies are screened for select inherited health conditions, expediting treatment for infants and reducing the chances they’ll experience long-term health consequences.

“The complexity of this program that is able to test nearly all 4 million babies in the U.S. each year is nothing short of astounding. You have to know the child is born – anywhere in the state – and then between 24 and 48 hours of birth you have to do testing onsite, obtain a specific type of blood sample, send the blood sample to an off-site lab quickly, test the sample, find the child if the test is out of range, get the child evaluated and tested for the condition, then send them for treatment. Given the time pressures as well as the coordination of numerous people and organizations, the fact that this happens routinely is amazing. And like any complex process, there is always room for improvement,” she says.

Dr. Tarini’s research efforts have focused on those process improvements.

As just one example, the Advisory Committee on Heritable Disorders in Newborns and Children, a federal advisory committee on which she serves, was discussing how to eliminate delays in specimen processing to provide speedier results to families. One possible solution floated was to open labs all seven days, rather than just five days a week. Dr. Tarini advocated for partnering with health care engineers who could help model ways to make the specimen transport process more efficient, just like airlines and mail delivery services. A more efficient and effective solution was to match the specimen pick-up and delivery times more closely with the lab’s operational times – which maximizes lab resources and shortens wait times for parents.

Conceptual modeling comes so easily for her that she often leaps out of her seat mid-sentence, underscoring a point by jotting thoughts on a white board, doing it so often that her pens have run dry.

“It’s like a bus schedule: You want to find a bus that not only takes you to your destination but gets you there on time,” she says.

Dr. Tarini’s current observational study looks for opportunities to improve how parents in Minnesota and Iowa are given out-of-range newborn screening test results – especially false positives – and how that experience might shake their confidence in their child’s health as well as heighten their own stress level.

“After a false positive test result, are there parents who walk away from newborn screening with lingering stress about their child’s health? Can we predict who those parents might be and help them?” she asks.

Among the challenges is the newborn screening occurs so quickly after delivery that some emotionally and physically exhausted parents may not remember it was done. Then they get a call from the state with ominous results. Another challenge is standardizing communication approaches across dozens of birthing centers and hospitals.

“We know parents are concerned after receiving a false positive result, and some worry their infant remains vulnerable,” she says. “Can we change how we communicate – not just what we say, but how we say it – to alleviate those concerns?”

Assorted foods

Tamp down food allergy anxieties with this quiz


toddler nursing

Newborns with suspected food allergies breastfed significantly longer

toddler nursing

Mothers whose newborns had suspected food allergies reported breastfeeding them significantly longer than women whose infants had no adverse reactions after food exposure, according to preliminary research led by Karen A. Robbins, M.D., and presented during the American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting.

According to the Centers for Disease Control and Prevention (CDC), food allergies affect 4 to 6 percent of U.S. children, making such allergies a growing public health concern. Researchers are attempting to learn more about the interplay between food allergies and what, when and how children eat to inform allergy-prevention efforts. Little is known about the association between perceived food allergies, intolerance or hypersensitivity among babies eating their first bites of solid food and how long they’re breastfed.

Dr. Robbins and colleagues analyzed data gathered through a longitudinal study led by the Food and Drug Administration (FDA) and the CDC from 2005 to 2007. The Infant Feeding Practices Study II tracked diet and feeding practices of about 2,000 women late in their pregnancies and followed their babies’ diets through the first year of life.

Some 2,586 breastfeeding mothers in the study completed surveys when their infants were 4, 9 and 12 months old. The women were asked whether there were problems caused by food, such as an allergic reaction, sensitivity or intolerance. The majority of these infants (84.6 percent) had no suspected allergic reaction to either food they ate on their own or to food they were exposed to via breastmilk. The mothers reported that nearly 11 percent of infants reacted to something they ate; 2.4 percent reacted to food products they were exposed to via breastmilk; and 2.4 percent reacted to both food they consumed directly or were exposed to via breastfeeding. They also found:

  • Infants with suspected food allergies after exposure to food their mothers ate were breastfed a mean of 45.8 weeks.
  • Infants with food intolerance after both exposure to food their mother consumed and food they ate themselves were breastfed a mean of 40.2 weeks.

That contrasts with infants with no concern for food reactions, who were breastfed a mean of 32 weeks.

“Breastfeeding a newborn for the first few months of life helps their developing immune system become more robust, may affect the microbiome, and could influence or prevent development of allergy later in life,” says Dr. Robbins, an allergist at Children’s National Health System and lead author of the research. “However, mothers’ perceptions of their newborns’ adverse reactions to food appears to factor into how long they breastfeed.”

One potential concern is that extended breastfeeding can impact solid food introduction practices.

“Gradually transitioning to solid food gives infants an opportunity to sample an array of foods, nibble by nibble, including food allergens like peanut and eggs. We know from previously published research that introducing high-risk babies to a food allergen like peanuts early in life appropriately primes their immune system and dramatically decreases how often these children actually develop peanut allergies,” Dr. Robbins adds. “The relationship between breastfeeding and allergy development is complex, so understanding mothers’ practices is important. We also do not know how often these early reactions result in true food allergy, compared with transient food intolerance.”

American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting presentation

  • “Perceived food allergy, sensitivity or intolerance and its impact on breastfeeding practices.”

Monday, Feb. 25, 2019, 9:45-10:45 a.m. (PST)

Karen A. Robbins M.D., lead author; Marni Jacobs, Ph.D., co-author; Ashley Ramos Ph.D., co-author; Daniel V. DiGiacomo, M.D., co-author; Katherine M. Balas BS, co-author; and Linda Herbert, Ph.D., director of Children’s Division of Allergy and Immunology’s psychosocial clinical program and senior author.

Breastfeeding Mom

Exclusive breastfeeding lowers odds of some schoolchildren having eczema

Breastfeeding Mom

Children exclusively breastfed for the first three months of life had significantly lower odds of having eczema at age 6 compared with peers who were not breastfed or were breastfed for less time, according to preliminary research presented during the American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting.

Eczema is a chronic condition characterized by extremely itchy skin that, when scratched, becomes inflamed and covered with blisters that crack easily. While genes and the environment are implicated in this inflammatory disease, many questions remain unanswered, such as how best to prevent it. According to the Centers for Disease Control and Prevention (CDC), breastfed infants have reduced risks for developing many chronic conditions, including asthma and obesity.

“The evidence that being exclusively breastfed protects children from developing eczema later in life remains mixed,” says Katherine M. Balas, BS, BA, a clinical research assistant at Children’s National and the study’s lead author. “Our research team is trying to help fill that data gap.”

Balas and colleagues tapped data collected in Infant Feeding Practices Study II, a longitudinal study co-led by the CDC and the Food and Drug Administration (FDA) from 2005 to 2007, as well as the agencies’ 2012 follow-up examination of that study cohort. This study first tracked the diets of about 2,000 pregnant women from their third trimester and examined feeding practices through their babies’ first year of life. Their follow-up inquiry looked at the health, development and dietary patterns for 1,520 of these children at 6 years of age.

About 300 of the children had been diagnosed with eczema at some point in their lives, and 58.5 percent of the 6-year-olds had eczema at the time of the CDC/FDA Year Six Follow-Up. Children with higher socioeconomic status or a family history of food allergies had higher odds of being diagnosed with eczema.

“Children who were exclusively breastfed for three months or longer were significantly less likely (adjusted odds ratio: 0.477) to have continued eczema at age 6, compared with peers who were never breastfed or who were breastfed for less than three months,” Balas adds. “While exclusive breastfeeding may not prevent kids from getting eczema, it may protect them from experiencing extended flare-ups.”

American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting presentation

  • “Exclusive breastfeeding in infancy and eczema diagnosis at 6 years of age.”

Sunday, Feb. 24, 2019, 9:45 a.m. (PST)

Katherine M. Balas BS, BA, lead author; Karen A. Robbins M.D., co-author; Marni Jacobs, Ph.D., co-author; Ashley Ramos Ph.D., co-author; Daniel V. DiGiacomo, M.D., co-author; and Linda Herbert, Ph.D., director of Children’s Division of Allergy and Immunology’s psychosocial clinical program and senior author.

Assorted foods

Food allergies: a research update

Assorted foods

Promising new therapies for food allergies are on the horizon, including an experimental immunotherapy awaiting federal approval that enables people who are very allergic to eat peanut protein without suffering serious side effects.

Good news, right?

As it turns out, the idea of a child who is highly allergic to a specific food eating that same food item makes kids with lifelong food allergies and their parents a bit queasy.

“It’s a very big paradigm shift. From diagnosis, children are told to avoid their food triggers at all cost. But now they may be counseled to approach the very thing that scares them, put it in their body and see what happens,” says Linda Herbert, Ph.D., an assistant professor in Children’s Division of Psychology and Behavioral Health.

“On the flip side, these new protections could reduce long-term anxieties, replacing daily anxiety about accidental exposure with a newfound sense of empowerment. Either way, a lot of families will need support as they try these new treatments that enable them to ingest a food allergen daily or wear a patch that administers a controlled dose of that food allergen,” Herbert says.

She will discuss food allergy treatments in the pipeline and families’ psychosocial concerns related to daily life as she presents a research update during the American Academy of Allergy, Asthma & Immunology (AAAAI) 2019 Annual Meeting. A select group, including Herbert, has been recognized with an AAAAI Foundation Heritage Lectureship, which honors distinguished AAAAI members with a special lecture and plaque.

Herbert’s symposium targets allied health professionals at the annual meeting, including psychologists, dietitians and nurse practitioners who attend to a host of psychosocial concerns felt by families affected by allergies to foods like eggs, nuts and cow’s milk.

“When patients arrive for outpatient therapy, they feel anxious about being safe when they’re out in public. They have anxieties about their children feeling safe at school as well as managing restaurant meals. They explain difficulties being included in social events like birthday parties, field trips and shared vacations,” Herbert says. “Some families restrict social activities due to stress and anxiety.”

Children’s National Health System takes a multidisciplinary approach for complex conditions like food allergies, she says, combining the expertise of psychologists, medical providers, research nurses, clinical nurses, registered dietitians and other allied health professionals.

“When we all communicate, we can see the complete picture. It strengthens the care that the child receives, and it’s especially powerful that it can happen all at once – rather than going to multiple appointments,” she adds.

During such group huddles, the team agrees on a plan together that is communicated to the family. One ongoing challenge is that one-third of school children with food allergies are bullied or teased.

“A lot of parents don’t necessarily know to ask or how to ask. I frequently suggest that clinicians discuss peer concerns more in clinic.”

American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting presentation

  • “Allied Health Plenary – Food Allergy Updates.”

Friday, Feb. 22, 2019, 4:15-5:30 p.m. (PST)

Linda Herbert, Ph.D., director of Children’s Division of Allergy and Immunology’s psychosocial clinical program.

pregnant woman holding eggs

How does diet during pregnancy impact allergies in offspring?

pregnant woman holding eggs

A small percentage of women said they consumed fewer allergens during pregnancy to stave off food allergies in their newborns, according to preliminary research Karen Robbins, M.D., presented during the American College of Asthma Allergy and Immunology 2018 Annual Scientific Meeting.

Pregnant women routinely swear off alcohol and tobacco to boost their chances of having a healthy baby. What about common food allergens like nuts and milk?

There are scant data that describe how often pregnant women deliberately stop eating a specific food item in order to prevent future food allergies in their newborns. As a first step toward addressing this data gap, a research team led by Karen Robbins, M.D., an allergist at Children’s National Health System, pored through a longitudinal study conducted by the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention.

About 4,900 pregnant women completed the Infant Feeding Practices Study II prenatal questionnaire from May 2005 to June 2007. The study tracked 2,000 pregnant women from the third trimester of pregnancy and their infants through the first year of life. A small percentage of women said they had consumed fewer allergens during pregnancy to stave off food allergies in their newborns, according to a poster Dr. Robbins presented during the American College of Asthma Allergy and Immunology 2018 Annual Scientific Meeting. While their numbers were small, most of these women reported giving up major allergens like nuts, milk or eggs during pregnancy, including:

  • 144 (2.9 percent) reported restricting their diet in some way to prevent future food allergies in their offspring
  • 84 women (1.7 percent) ate fewer nuts
  • 15 women (.3 percent) ate fewer eggs and
  • 2 women (.04 percent) ate/drank consumed less dairy/milk.

“At the time the survey was conducted, few pregnant women in this large data set said they gave up certain foods with the express aim of avoiding a food allergy in their babies,” Dr. Robbins says. “However, mothers who had an older child with a food allergy or who had food allergies themselves had significantly higher odds of trying this food avoidance strategy.”

Despite the diet changes, infants born to these expectant mothers were twice as likely to experience problems with food at age 4 months – though not at age 9 months or 12 months. And these infants were no more likely to be diagnosed with a food allergy.

According to the FDA, millions of Americans suffer a food allergy each year. Reactions can range from mild to life-threatening and can begin soon after eating a problematic food item or an ingredient from that food. Among the most common allergenic foods are milk, eggs, fish, shellfish, tree nuts, peanuts, wheat and soybeans.

“We really need to know more about how often targeted food avoidance occurs among U.S. pregnant women who have a family history of food allergies,” Dr. Robbins adds. “We hope to learn what factors into these women’s decision-making as well as why many of them settled on food avoidance as a potential strategy to try to prevent food allergy in their infants.”

American College of Asthma Allergy and Immunology 2018 Annual Scientific Meeting presentation

  • “Prenatal food allergen avoidance practices for food allergy prevention.”

Karen Robbins M.D., lead author; Ashley Ramos Ph.D., co-author; Marni Jacobs, Ph.D., co-author; Kate Balas BS, co-author; and Linda Herbert, Ph.D., director of Children’s Division of Allergy and Immunology’s psychosocial clinical program, and senior author.

Making the grade: Children’s National is nation’s Top 5 children’s hospital

Children’s National rose in rankings to become the nation’s Top 5 children’s hospital according to the 2018-19 Best Children’s Hospitals Honor Roll released June 26, 2018, by U.S. News & World Report. Additionally, for the second straight year, Children’s Neonatology division led by Billie Lou Short, M.D., ranked No. 1 among 50 neonatal intensive care units ranked across the nation.

Children’s National also ranked in the Top 10 in six additional services:

For the eighth year running, Children’s National ranked in all 10 specialty services, which underscores its unwavering commitment to excellence, continuous quality improvement and unmatched pediatric expertise throughout the organization.

“It’s a distinct honor for Children’s physicians, nurses and employees to be recognized as the nation’s Top 5 pediatric hospital. Children’s National provides the nation’s best care for kids and our dedicated physicians, neonatologists, surgeons, neuroscientists and other specialists, nurses and other clinical support teams are the reason why,” says Kurt Newman, M.D., Children’s President and CEO. “All of the Children’s staff is committed to ensuring that our kids and families enjoy the very best health outcomes today and for the rest of their lives.”

The excellence of Children’s care is made possible by our research insights and clinical innovations. In addition to being named to the U.S. News Honor Roll, a distinction awarded to just 10 children’s centers around the nation, Children’s National is a two-time Magnet® designated hospital for excellence in nursing and is a Leapfrog Group Top Hospital. Children’s ranks seventh among pediatric hospitals in funding from the National Institutes of Health, with a combined $40 million in direct and indirect funding, and transfers the latest research insights from the bench to patients’ bedsides.

“The 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver exceptional care across a range of specialties and deserve to be highlighted,” says Ben Harder, chief of health analysis at U.S. News. “Day after day, these hospitals provide state-of-the-art medical expertise to children with complex conditions. Their U.S. News’ rankings reflect their commitment to providing high-quality care.”

The 12th annual rankings recognize the top 50 pediatric facilities across the U.S. in 10 pediatric specialties: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology and urology. Hospitals received points for being ranked in a specialty, and higher-ranking hospitals receive more points. The Best Children’s Hospitals Honor Roll recognizes the 10 hospitals that received the most points overall.

This year’s rankings will be published in the U.S. News & World Report’s “Best Hospitals 2019” guidebook, available for purchase in late September.

inhaler

Keeping kids with asthma out of the hospital

inhaler

Pediatric asthma takes a heavy toll on patients and families alike. Affecting more than 7 million children in the U.S., it’s the most common nonsurgical diagnosis for pediatric hospital admission, with costs of more than $570 million annually. Understanding how to care for these young patients has significantly improved in the last several decades, leading the National Institutes of Health (NIH) to issue evidence-based guidelines on pediatric asthma in 1990. Despite knowing more about this respiratory ailment, overall morbidity – measured by attack rates, pediatric emergency department visits or hospitalizations – has not decreased over the last decade.

“We know how to effectively treat pediatric asthma,” says Kavita Parikh, M.D., M.S.H.S., a pediatric hospitalist at Children’s National Health System. “There’s been a huge investment in terms of quality improvements that’s reflected in how many papers there are about this topic in the literature.”

However, Dr. Parikh notes, most of those quality-improvement papers do not focus on inpatient discharge, a particularly vulnerable time for patients. Up to 40 percent of children who are hospitalized for asthma-related concerns come back through the emergency department within one year. One-quarter of those kids are readmitted.

“It’s clear that we need to do better at keeping kids with asthma out of the hospital. The point at which they’re being discharged might be an effective time to intervene,” Dr. Parikh adds.

To determine which interventions hold promise, Dr. Parikh and colleagues recently performed a systematic review of studies involving quality improvements after inpatient discharge. They published their findings in the May 2018 edition of the journal, Pediatrics. Because May is National Asthma and Allergy Awareness month, she adds, it’s a timely fit.

The researchers combed the literature, looking for research that tested various interventions at the point of discharge for their effect on hospital readmission anywhere from fewer than 30 days after discharge to up to one year later. They specifically searched for papers published from 1991, the year after the NIH issued its original asthma care guidelines, until November 2016.

Their search netted 30 articles that met these criteria. A more thorough review of each of these studies revealed common themes to interventions implemented at discharge:

  • Nine studies focused on standardization of care, such as introducing or revising a specific clinical pathway
  • Nine studies focused on education, such as teaching patients and their families better self-management strategies
  • Five studies focused on tools for discharge planning, such as ensuring kids had medications in-hand at the time of discharge or assigning a case manager to navigate barriers to care and
  • Seven studies looked at the effect of multimodal interventions that combined any of these themes.

When Dr. Parikh and colleagues examined the effects of each type of intervention on hospital readmission, they came to a stunning conclusion: No single category of intervention seemed to have any effect. Only multimodal interventions that combined multiple categories were effective at reducing the risk of readmission between 30 days and one year after initial discharge.

“It’s indicative of what we have personally seen in quality-improvement efforts here at Children’s National,” Dr. Parikh says. “With a complex condition like asthma, it’s difficult for a single change in how this disease is managed to make a big difference. We need complex and multimodal programs to improve pediatric asthma outcomes, particularly when there’s a transfer of care like when patients are discharged and return home.”

One intervention that showed promise in their qualitative analysis of these studies, Dr. Parikh adds, is ensuring patients are discharged with medications in hand—a strategy that also has been examined at Children’s National. In Children’s focus groups, patients and their families have spoken about how having medications with them when they leave the hospital can boost compliance in taking them and avoid difficulties is getting to an outside pharmacy after discharge. Sometimes, they have said, the chaos of returning home can stymie efforts to stay on track with care, despite their best efforts. Anything that can ease that burden may help improve outcomes, Dr. Parikh says.

“We’re going to need to try many different strategies to reduce readmission rates, engaging different stakeholders in the inpatient and outpatient side,” she adds. “There’s a lot of room for improvement.”

In addition to Dr. Parikh, study co-authors include Susan Keller, MLS, MS-HIT, Children’s National; and Shawn Ralston, M.D., M.Sc., Children’s Hospital of Dartmouth-Hitchcock.

Funding for this work was provided by the Agency for Healthcare Research and Quality (AHRQ) under grant K08HS024554. The content is solely the responsibility of the authors and does not necessarily represent the official views of AHRQ.

Gustavo Nino

New method may facilitate childhood respiratory research

Gustavo Nino

“The use of CRC is a potentially powerful translational approach to shed light on the molecular mechanisms that control airway epithelial immune responses in infants and young children. This novel approach enables us to study the origins of respiratory disease and its chronic progression through childhood and beyond,” observes Gustavo Nino, M.D., a Children’s pulmonologist and study senior author.

A new method perfected by a team at Children’s National Health System may help expand research into pulmonary conditions experienced by infants and children, an understudied but clinically important age group. The study describing the new technique was published in the December 2017 print edition of Pediatric Allergy and Immunology.

Using conditionally reprogrammed cells (CRCs), a technique that enables indefinite proliferation of cells in the lab, the team was able to produce cell cultures that have a number of advantages over standard cultures and that may make it easier and more efficient to conduct research into pediatric respiratory immune responses.

The epithelial cells that line human airways are crucial in controlling immune responses to viruses, allergens and other environmental factors. The function and dysfunction of these airway epithelial cells (AECs) play a key role in asthma, cystic fibrosis and other pulmonary conditions, many of which begin in early life.

To generate enough of these cells for research, scientists culture AECs from primary nasal and bronchial cell samples. Cells derived from adults have fueled research leading to new therapies and the discovery of key biomarkers. But little comparable research has been conducted in infants. Airway sampling in premature infants has not been reported, likely to due to airway size limitations and underlying comorbidities. Similarly, sampling in infants is limited by the need for bronchoscopy and sedation.

“A major barrier has been the lack of a good system to culture epithelial cells, since airway sampling in infants and children is a challenge,” says co-lead author, Geovanny F. Perez, M.D., co-director of Children’s Severe Bronchopulmonary Dysplasia Program. “We needed a better way to culture cells in this age group.”

While primary AECs do not survive long in the lab, that hurdle was recently overcome by a process that generates CRCs from the primary AECs of adults, making it possible to quickly generate cell cultures from specimens.

In this study, the Children’s team adapted that approach, producing CRCs from primary AECs of neonates and infants. The CRC induction successfully enabled AEC cultures from infants born prematurely and from bronchial specimens of young children.

Geovanny Perez

“A major barrier has been the lack of a good system to culture epithelial cells, since airway sampling in infants and children is a challenge,” says co-lead author, Geovanny F. Perez, M.D., co-director of Children’s Severe Bronchopulmonary Dysplasia Program. “We needed a better way to culture cells in this age group.”

“We found that the CRCs have longer cell life and greater proliferation ability than standard cultures of epithelial cells. They preserved their original characteristics even after multiple experiments. And, they presented an innate immune response similar to that seen in primary human epithelial cells during viral respiratory responses in children,” says Dr. Perez.

“The use of CRC is a potentially powerful translational approach to shed light on the molecular mechanisms that control airway epithelial immune responses in infants and young children. This novel approach enables us to study the origins of respiratory disease and its chronic progression through childhood and beyond,” observes Gustavo Nino, M.D., a Children’s pulmonologist and study senior author.

The authors note that further studies are needed to define more precisely the differences and similarities in the immune responses of CRC and non-CRC derived from primary AEC. However, they conclude that CRC represents a new, effective method to study AEC innate immune responses in infants.

In addition to Drs. Perez and Nino, Children’s Center for Genetic Medicine Research co-authors include Co-Lead Author S. Wolf; Lana Mukharesh; Natalia Isaza Brando, M.D.; Diego Preciado, M.D., Ph.D.; Robert J. Freishtat, M.D., M.P.H.; Dinesh Pillai, M.D.; and M. C. Rose.

Financial support for this research was provided by the National Institute of Allergy and Infectious Diseases under grant number R21AI130502; Eunice Kennedy Shriver National Institute of Child Health and Human Development under grant number HD001399; National Heart, Lung and Blood Institute under grant number HL090020; and National Center for Advancing Translational Sciences under grant number UL1TR000075.

chromosome

X-linked genes help explain why boys of all ages face higher respiratory risk

chromosome

A multi-institution research team that includes Children’s National Health System attempted to characterize gender-based epigenomic signatures in the human airway early in children’s lives with a special attention to defining DNA methylation patterns of the X chromosome.

Human airways already demonstrate gender-based differences in DNA methylation signatures at birth, providing an early hint of which infants may be predisposed to develop respiratory disorders like asthma later in life, a research team reports in a paper published online April 3, 2018, in Scientific Reports.

It’s clear that boys and young men are more likely to develop neonatal respiratory distress syndrome, bronchopulmonary dysplasia, viral bronchiolitis, pneumonia, croup and childhood asthma. Unlike boys, girls have an additional copy of the X chromosome, which is enriched with immune-related genes, some of which play key roles in the development of respiratory conditions. Methylation prevents excessive gene activity in X-linked genes, however much remains unknown about how this process influences infants’ risk of developing airway diseases.

A multi-institution research team that includes Children’s National Health System attempted to characterize gender-based epigenomic signatures in the human airway early in children’s lives with a special attention to defining DNA methylation patterns of the X chromosome.

“It’s clear as we round in the neonatal intensive care unit that baby boys remain hospitalized longer than girls and that respiratory ailments are quite common. Our work provides new insights about gender differences in airway disease risk that are pre-determined by genetics,” says Gustavo Nino, M.D., a Children’s pulmonologist and the study’s senior author.

“Characterizing early airway methylation signatures holds the promise of clarifying the nature of gender-based disparities in respiratory disorders and could usher in more personalized diagnostic and therapeutic approaches.”

The research team enrolled 12 newborns and infants in the study and obtained their nasal wash samples. Six of the infants were born preterm, and six were born full term. The researchers developed a robust gender classification algorithm to generate DNA methylation signals. The machine learning algorithm identified X-linked genes with significant differences in methylation patterns in boys, compared with girls.

As a comparison group, they retrieved pediatric nasal airway epithelial cultures from a study that looked at genomic DNA methylation patterns and gene expression in 36 children with persistent atopic asthma compared with 36 heathy children.

The team went on to classify X-linked genes that had significant gender-based X methylation and those genes whose X methylation was variable.

“These results confirm that the X chromosome contains crucial information about gender-related genetic differences in different airway tissues,” Dr. Nino says. “More detailed knowledge of the genetic basis for gender differences in the respiratory system may help to predict, prevent and treat respiratory disorders that can affect patients over their entire lifetimes.”

In addition to Dr. Nino, study co-authors include Lead Author Cesar L. Nino, bioinformatics scientist, Pontificia Universidad Javeriana; Geovanny F. Perez, M.D., co-director of Children’s Severe Bronchopulmonary Dysplasia Program; Natalia Isaza Brando, M.D., Children’s neonatology attending; Maria J. Gutierrez, Johns Hopkins University School of Medicine; and Jose L. Gomez, Yale University School of Medicine.

Financial support for this research was provided by the National Institutes of Health under award numbers
AI130502-01A1, HL090020, HL125474-03, HD001399, UL1TR000075 and KL2TR000076.

Kavita Parikh

Discharge strategies to prevent asthma readmissions

“Improving how we care for children who are hospitalized with asthma includes preparing them for a successful return home with the best tools to manage their illness and prevent a future hospital visit,” says Kavita Parikh, M.D., M.S.H.S.

Readmission rates at three months for kids hospitalized for acute asthma dropped when families received comprehensive education prior to discharge, the only single component of discharge bundles that was strongly associated with lowered readmissions, finds a multicenter retrospective cohort study published online Feb. 1, 2018, in The Journal of Pediatrics.

According to the Centers for Disease Control and Prevention, asthma is the most common chronic lung disease of childhood, affecting roughly 6 million U.S. children. Hospitalization for asthma accounts for $1.5 billion in annual hospital charges and represents almost one-third of childhood asthma costs.

Children who are hospitalized for asthma have a roughly 20 percent chance of returning to the hospital in the next year, and individual hospital readmission rates can range from 5.7 percent to 9.1 percent at three months, writes the study team. While the National Institutes of Health (NIH) has published evidence-based guidelines for discharge planning, there is no single, standardized asthma discharge process used across all pediatric hospitals in the U.S. that impacts 30-day readmission rates.

“Improving how we care for children who are hospitalized with asthma includes preparing them for a successful return home with the best tools to manage their illness and prevent a future hospital visit,” says Kavita Parikh, M.D., M.S.H.S., an associate professor of pediatrics at Children’s National Health System and lead study author. “Our study underscores the importance of increasing the intensity of select discharge components. For example, ensuring that children hospitalized for asthma receive asthma medication at discharge along with comprehensive education and environmental mitigation may reduce asthma readmissions.”

The study team analyzed records from a national sample of tertiary care children’s hospitals, looking at hospitalizations of 5- to 17-year-olds for acute asthma exacerbation during the 2015 calendar year. They characterized how frequently hospitals used 13 separate asthma discharge components by distributing an electronic survey to quality leaders. Forty-five of 49 hospitals (92 percent) completed the survey.

The 45 hospitals recorded a median of 349 asthma discharges per year and had a median adjusted readmission rate of 2.6 percent at 30 days and a 6.6 percent median adjusted readmission rate at three months. The most commonly used discharge components employed for children with asthma were having a dedicated person providing education (76 percent), providing a spacer at discharge (67 percent) and communicating with a primary medical doctor (58 percent).

Discharge components that were trending toward reduced readmission rates at three months include:

  • Comprehensive asthma education, including having dedicated asthma educators
  • Medications and devices provided to patients at discharge, such as spacers, beta-agonists, controller medication and oral steroids
  • Communication and scheduled appointments with a primary medical doctor
  • Post-discharge activities, including home visits and referrals for environmental mitigation programs.

“In addition to being aligned with NIH asthma recommendations, connecting the family with a primary care provider after discharge helps to improve patients’ timely access to care if symptoms recur when they return home,” Dr. Parikh adds. “Bundling these discharge components may offer multiple opportunities to educate patients and families and to employ a range of communication styles such as didactic, visual and interactive.”

Study co-authors include Matt Hall, Ph.D., Children’s Hospital Association; Chén C. Kenyon, M.D., M.S.H.P., The Children’s Hospital of Philadelphia; Ronald J. Teufel II, M.D., M.S.C.R., Medical University of South Carolina; Grant M. Mussman, M.D., M.H.S.A. and Samir S. Shah, M.D., M.S.C.E., Cincinnati Children’s Hospital Medical Center; Amanda Montalbano, M.D., M.P.H., Children’s Mercy; Jessica Gold, M.D., M.S., Lucile Packard Children’s Hospital Stanford; James W. Antoon, M.D., Children’s Hospital; Anupama Subramony, M.D., Cohen Children’s Medical Center; Vineeta Mittal, M.D., M.B.A. and Rustin B. Morse, M.D., Children’s Health; and Karen M. Wilson, M.D., M.P.H., Icahn School of Medicine at Mount Sinai.

Research reported in this post was supported by the Agency for Healthcare Research and Quality, K08HS024554.

Human Rhinovirus

When a common cold may trigger early supportive care

Human Rhinovirus

A new study led by Children’s National Health System shows that in infants who were born severely premature, human rhinovirus infections appear to trigger airway hyper-reactivity, which leads to wheezing, hyperinflation and more severe respiratory disease.

Human rhinovirus (HRV), the culprit behind most colds, is the leading cause of hospitalization for premature babies. However, in very preterm children, exactly how HRV causes severe respiratory disease – and which patients may need more intensive observation and treatment – is less well understood.

A new study led by Children’s National Health System research-clinicians showed in children who were born severely premature, HRV infections seem to trigger an airway hyper-reactivity (AHR) type of disease, which leads to wheezing and air-trapping (hyperinflation) and more severe respiratory disease. This, in turn, increases the risk for hospitalization.

The study, published online Oct. 21, 2017 in Pediatrics and Neonatology, found that other signs of respiratory distress, such as low arterial blood oxygen or rapid shallow breathing, were no more common in severely premature children (less than 32 weeks of gestational age) than in kids born preterm or full-term. The findings have implications for administering supportive care sooner or more intensively for severely premature children than for other infants.

“When it comes to how they respond to such infections, severely premature children are quite different,” says Geovanny Perez, M.D., a specialist in pulmonary medicine at Children’s National and lead study author. “We’ve known they are more susceptible to human rhinovirus infection and have more severe disease. However, our study findings suggest that severely premature kids have an ‘asthma’ type of clinical picture and perhaps should be treated differently.”

The study team sought to identify clinical phenotypes of HRV infections in young children hospitalized for such infections. The team theorized that severely premature babies would respond differently to these infections and that their response might resemble symptoms experienced by patients with asthma.

“For a number of years, our team has studied responses to viruses and prematurity, especially HRV and asthma,” Dr. Perez says. “We know that premature babies have an immune response to HRV from the epithelial cells, similar to that seen in older patients with asthma. But we wanted to address a gap in the research to better understand which children may need closer monitoring and more supportive care during their first HRV infection.”

Geovanny Perez

“When it comes to how they respond to such infections, severely premature children are quite different,” says Geovanny Perez, M.D. “We’ve known they are more susceptible to human rhinovirus infection and have more severe disease. However, our study findings suggest that severely premature kids have an ‘asthma’ type of clinical picture and perhaps should be treated differently.”

In a retrospective cross-sectional analysis, the study looked at 205 children aged 3 years or younger who were hospitalized at Children’s National in 2014 with confirmed HRV infections. Of these, 71 percent were born full-term (more than 37 gestational weeks), 10 percent were preterm (32 to 37 gestational weeks) and 19 percent were severely premature (less than 32 gestational weeks).

Dr. Perez and his team developed a special respiratory distress scoring system based on physical findings in the children’s electronic medical records to assess the degree of lower-airway obstruction or AHR (as occurs in asthma) and of parenchymal lung disease. The physical findings included:

  • Wheezing;
  • Subcostal retraction (a sign of air-trapping/hyperinflation of the lungs), as can occur in pneumonia;
  • Reduced oxygen levels (hypoxemia); and
  • Increased respiratory rate (tachypnea).

The research team assigned each case an overall score. The severely premature children had worse overall scores – and significantly worse scores for AHR and hyperinflated lungs relative to children born late preterm or full-term.

“What surprised us, though, in this study was that the phenotypical characterization using individual parameters for parenchymal lung disease, such as hypoxemia or tachypnea, were not different in severe preterm children and preterm or full term,” says Dr. Perez. “On the other hand, our study found that severely preterm children had a lower airway obstruction phenotype associated with retractions and wheezing. Moreover there was a ‘dose effect’ of prematurity: Children who were born more premature had a higher risk of wheezing and retractions.”

Among the implications of this study, Dr. Perez sees the potential to use phenotypical (clinical markers, such as retractions and wheezing) and biological biomarkers to better personalize patients’ treatments. Dr. Perez and his team have identified biological biomarkers in nasal secretions of children with rhinovirus infection that they plan to combine with clinical biomarkers to identify which patients with viral infections will benefit from early supportive care, chronic treatments or long-term monitoring.

Dr. Perez says further research in this area should pursue a number of paths, including:

  • A longitudinal study to elucidate which children will benefit from asthma-like treatment, such as bronchodilators or corticosteroids;
  • A study of biomarkers, including microRNAs and other inflammatory molecules; or
  • Alternatively, a longitudinal study exploring the mechanism by which wheezing develops, perhaps looking at first and subsequent rhinovirus infections in babies born at different gestational ages.
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.