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:
- BreatheDC, a non-profit that fights all forms of lung disease
- Local Initiatives Support Corporation of DC, the nation’s largest community development support organization
- The Institute of Public Health Innovation, a non-profit whose work enhances conditions in which people live, work and play
- Yachad, which preserves affordable housing
- IMPACT DC, Children’s award-winning pediatric asthma program
- Child Health Advocacy Institute, based at Children’s National
- Goldberg Center for Community Pediatric Health, Children’s primary care practices and
- Children’s Telemedicine, which delivers health care remotely using technology.
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.
Pulmonologists have often observed a link between asthma and the need for continuous positive airway pressure treatment (CPAP) among children with severe obstructive sleep apnea syndrome (OSAS).
Now, research published in the March 2019 issue of the journal Pediatric Pulmonology confirms the correlation.
Four-hundred eligible children with severe OSAS were included in a randomized, controlled study that took place at Children’s National Health System between September 2015 and June 2017. The mean age among study participants, ages 0 to 20, was 7.
Out of the 400 severe OSAS study participants, 113 children, about one-third, had asthma. Those with asthma were 29% more likely to require CPAP, compared to 14% of study participants without asthma. This association was independent of demographics, OSAS severity, obesity and a history of adenotonsillectomy, an operation to remove the tonsils.
“This is the first randomized, controlled study to test the association between asthma and CPAP among children with severe sleep apnea,” says Gustavo Nino, M.D., a corresponding study author, a pediatric pulmonologist and the director of sleep medicine at Children’s National Health System. “We’ve seen similar patterns in adults, but we needed to confirm the link in children to provide preventive screenings and personalized treatment.”
Dr. Nino mentions the goal now is to detect symptoms earlier, whether this occurs at an annual wellness exam with a pediatrician or at the first visit with a sleep medicine specialist.
“The next step for our research team, or for others interested in this topic, is to explore how these factors influence each other,” adds Dr. Nino. “Asthma itself is worse when you sleep. This leads us to wonder if obstructive sleep apnea exacerbates symptoms of asthma. Or could controlling asthma decrease the risk for CPAP therapy among children with severe obstructive sleep apnea?”
Until these questions have answers, Dr. Nino encourages pediatricians and specialists to keep the association in mind, especially since 7 million children nationwide have asthma, including 13,981 children in the District.
Parents should know that children who have severe obstructive sleep apnea and asthma are more likely to need extensive treatment, like CPAP, to maintain a positive flow of air to the nasal passages to keep the airway open.
Managing symptoms of asthma is also something parents can do at home, especially with the onset of spring asthma triggers, such as pollen, dust, dander, mold and smoke.
For help creating an asthma action plan, visit the Centers for Disease Control and Prevention.
Two doctors from Children’s National Health System are among the recipients of the 40 Under 40 Leaders in Minority Health award by the National Minority Quality Forum (NMQF) for 2019. Kofi Essel, M.D., M.P.H., is a pediatrician, Ankoor Shah, M.D., M.B.A., M.P.H., is the medical director of the IMPACT DC Asthma Clinic and also a pediatrician at Children’s National.
Founded in 1998, the NMFQ is dedicated to ensuring that high-risk racial and ethnic populations and communities receive optimal health care. The 40 individuals selected for this award represent the next generation of thought leaders in reducing health disparities.
Dr. Kofi Essel is a pediatrician at the Children’s Health Center Anacostia. His focus and research has been around health equity, obesity, food insecurity and nutrition.
“Hunger strikes so many of our families,” says Dr. Essel, “In D.C., we were number one in the nation for having the highest rate of food hardship in households with children.”
Dr. Essel is involved with many organizations and initiatives that raise awareness about hunger and how much of an issue it is. He strives to be a partner for the families that he serves, many of whom are in the fight against obesity, and works alongside them to improve their overall health.
“It’s a huge honor to receive recognition from this national organization,” says Dr. Kofi Essel, “Ultimately, it allows us to have a bit more of a platform to continue to advance some of the great work we’re doing with health disparities.”
Dr. Ankoor Shah is the medical director for IMPACT DC asthma clinic and a pediatrician at the Children’s Health Center at THEARC. His focus includes improving pediatric population health and reducing child health asthma disparities.
“Through the coordination of the best in class care at Children’s National with amazing on the ground community partners, we have been able to transform the lives of the most at-risk children with asthma” says Dr. Shah.
Dr. Shah collaborates with organizations to improve the outcomes of kids with asthma by targeting intervention in high-risk areas.
“This award is recognition of the great work we’re doing in terms of improving asthma health in high-risk child populations throughout the District of Columbia.”
Both Dr. Essel and Dr. Shah are from Arkansas, attended Emory University and they did their residency together at Children’s National.
Congratulations to these wonderful doctors and leaders for receiving this award.
The 40 Under 40 recipients received their awards at the 2019 NMQF Leadership Summit on Health Disparities and CBC Spring Health Braintrust Gala Dinner on April 9.
Children’s National physicians Anastassios Koumbourlis, M.D., M.P.H, division chief of Pulmonary and Sleep Medicine, and Geovanny Perez, M.D., attending pulmonologist and asthma researcher, co-authored a recent article published in the Annals of the American Thoracic Society entitled “Heterogeneity in the Diagnostic Criteria Physicians use in Pediatric Asthma.” Their study focused on the term “physician-diagnosed asthma” (PDA) that is commonly used, especially in research, as a specific characteristic that allow the stratification of patients to different groups (e.g. those with PDA vs. those without PDA). The term simply means that a patient has been given the diagnosis of asthma by a physician without any explanation as to how the diagnosis was made. Drs. Koumbourlis and Perez challenge the validity of the term on the grounds that “asthma is often misdiagnosed, because there are no consistencies in the criteria physicians use to make the diagnosis.”
To prove their theory, a survey was sent to pediatric pulmonologists and general pediatricians to identify the clinical and laboratory criteria they use to diagnose pediatric asthma. The responses were tabulated separately for the two groups. In total, 205 pediatric pulmonologists from 24 different countries and 111 general pediatricians responded to the survey.
The results revealed substantial variability between pulmonologists and general pediatricians:
- “‘Resolution of symptoms after treatment with bronchodilators’ was the most frequently (85 percent) chosen criterion by pulmonologists, followed by ‘symptoms on exertion’ and ‘recurrent/persistent cough in the absence of infection’ (55 percent and 35 percent, respectively). Non-pulmonologists chose equally the presence of ‘symptoms on exertion’ and the ‘resolution of symptoms with bronchodilators’ (76 percent and 74 percent, respectively), followed by ‘recurrent/persistent cough’ (38 percent).
- “There were striking differences in the use of diagnostic tests between the two groups. Almost all pulmonologists (91 percent) chose spirometry before and after the bronchodilator as part of their diagnosis. They were also significantly more likely to use other tests. In contrast, two-thirds of the non-pulmonologists (64 percent) do not use any tests.”
The results of the survey reveal noteworthy discrepancies not only between practice and guidelines, but more importantly between physicians, often determined by their specialty. This variability in the diagnostic criteria for asthma means that patients who are assigned as having PDA do not necessarily represent a homogeneous population. This, in turn, may significantly affect the results of research studies that use the term PDA to categorize patients into different groups. Thus, the investigators conclude, the term PDA should either be avoided completely or, if it must be used, it should be accompanied by the specific criteria on which the diagnosis was based.
Stephen J. Teach, M.D., M.P.H., has been named the inaugural Wendy Goldberg Professor in Translational Research in Child Health and Community Partnerships. This professorship comes with an endowed chair at Children’s National Health System.
The prestigious honor is given for the duration of Dr. Teach’s (and future chair holders’) employment at Children’s National. The award’s namesake, Wendy Goldberg, and her husband, Fred T. Goldberg Jr., are among the brightest stars in the constellation of Children’s National supporters, says Dr. Teach, Associate Dean for Pediatric Academic Affairs and Chair of the Department of Pediatrics at The George Washington University School of Medicine & Health Sciences.
In addition to serving on many Children’s boards, in the mid-2000s the Goldbergs made a $250,000 gift that benefited Improving Pediatric Asthma Care in the District of Columbia (IMPACT DC), Dr. Teach’s award-winning program to improve clinical care, empower patients and families, and conduct new research to improve patients’ outcomes.
“In recognition of the anchor aims of Children’s new strategic plan, the Goldbergs wanted this new gift to focus on the intersection of community health and research,” Dr. Teach says. “Thanks to their generosity, my team will work with community partners to use data to drive improvements in population health.”
With the dedicated funding Dr. Teach was able to hire a new staffer, Caitlin Munoz, to help mine electronic health records to create disease-specific registries that include 15,000 children and adolescents – the lion’s share of kids younger than 17 who live in Washington and have asthma.
“For the first time, we will be able to describe in granular detail the near-universe of local children who have this chronic respiratory disease,” he says. “We will be able to describe many of the most clinically meaningful aspects of nearly every child with asthma who lives in D.C., including mean age, gender, ethnicity and mean number visits to the emergency department.”
Such a richly textured database will help identify children who should be prescribed daily controller medications to help them avoid missing school days due to asthma exacerbations, he says. The next pediatric chronic disease they will track via registry will be pediatric obesity via elevated body mass index.
“That, in and of itself, is insightful data. But the enduring impact of this applied research is it will inform our continuous quality-improvement efforts,” he adds.
By querying the registries the team will be able to tell, for example, how Children’s primary care centers rank comparatively by asking such questions as which percentage of kids with asthma actually take the medicines they had been prescribed the year prior.
“Increasingly, clinical research falls into one of two buckets. You can either do better things: That’s discovering new drugs or processes, like our ongoing clinical trial to desensitize kids to asthma allergens. Or, you can do things better. We often know what to do already. We know that guideline-based asthma care works well. We don’t need to prove that again. We just need to do things better by getting this care to the kids who need it. That’s where this line of research/quality improvement comes in: It’s getting people to do things better.”
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.
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.
In 2017, clinicians and research faculty working at Children’s National Health System published more than 850 research articles about a wide array of topics. A multidisciplinary Children’s Research Institute review group selected the top 10 articles for the calendar year considering, among other factors, work published in high-impact academic journals.
“This year’s honorees showcase how our multidisciplinary institutes serve as vehicles to bring together Children’s specialists in cross-cutting research and clinical collaborations,” says Mark L. Batshaw, M.D., Physician-in-Chief and Chief Academic Officer at Children’s National. “We’re honored that the National Institutes of Health and other funders have provided millions in awards that help to ensure that these important research projects continue.”
The published papers explain research that includes using imaging to describe the topography of the developing brains of infants with congenital heart disease, how high levels of iron may contribute to neural tube defects and using an incisionless surgery method to successfully treat osteoid osteoma. The top 10 Children’s papers:
- The role of reactive oxygen species in starting the process of repairing myofiber
- The importance of restoring neural stem/progenitor cells’ neurogenic potential to lessen long-term neurological deficits
- Functional impairment of the brains of infants with congenital heart disease prior to corrective open heart surgery
- Altered regional cerebral blood flow as an early warning sign of disturbed brain maturation
- Excess production of transcription factor Heat Shock Factor 1 can contribute to impairing the embryonic brain
- High levels of iron supplementation and iron overload may contribute to neural tube defects
- In a small study, 18F-fluorothymidine imaging identified subclinical bone-marrow recovery within five days of allogenic haemopoietic stem-cell infusion
- An experimental model exposed to di-2-ethylhexyl-phthalate experienced altered autonomic regulation, heart rate variability and cardiovascular reactivity
- Osteoid osteoma can be safely treated using magnetic resonance-guided high-intensity focused ultrasound and
- Racial and ethnic disparities in pediatric readmission rates vary for chronic conditions such as asthma, depression, diabetes, migraines and seizures.
Read the complete list.
Dr. Batshaw’s announcement comes on the eve of Research and Education Week 2018 at Children’s National, a weeklong event that begins April 16, 2018. This year’s theme, “Diversity powers innovation,” underscores the cross-cutting nature of Children’s research that aims to transform pediatric care.
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 (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.”
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:
- 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.
For hundreds of years, scientific and medical research has followed a process that practically all grade-school children learn as the scientific method: Scientists make observations that lead to a question. After developing a hypothesis, the researchers and colleagues — usually other scientists in the same field — test it by gathering data from experiments, making more observations or searching through the existing literature. Once they have an answer, the researchers often publish it in a scientific journal, which can generate new questions among peer scientists and starts the cycle all over again.
While most research is meant to benefit humankind as a whole, non-scientists and people who aren’t research subjects usually aren’t involved much in the process itself. That can be a serious omission, particularly for medical research, says Stephen J. Teach, M.D., M.P.H., chair of the Department of Pediatrics at Children’s National Health System, and Deborah Quint Shelef, M.P.H., C.C.R.P., AE-C., program director at IMPACT DC, a program at Children’s National Health System that helps patients effectively manage asthma.
“Our patients might view research a little differently than we do. They don’t just want general contributions to knowledge, but specific contributions that people can actually use,” Shelef says. “One of our main goals is to have useful research models that can translate into changes that really improve patient care. It’s hard to make this happen without asking people who are affected most what would address their needs.”
That’s why Shelef and Dr. Teach’s most recent study, featured on the cover of the December 2016 issue of The Journal of Allergy and Clinical Immunology, shifts the research paradigm from a scientist-centered model to what they call a stakeholder-centered approach. Rather than develop the study solely with fellow researchers, the research team led by Children’s National relied heavily on guidance from people who would be most impacted by the results.
The study focused on whether an intervention that reduced parental stress could improve asthma outcomes among low-income African American children. To help design their study, the research team looked to several different sources for advice: African American parents of children treated for asthma at Children’s National; local providers of social, medical, legal and educational services; and experts in psychosocial stress, medication adherence and conducting studies among at-risk youth with asthma.
The researchers gave themselves one year to consult multiple times with each stakeholder group before starting to enroll study subjects in May 2015. In the initial planning phases, the research team intended to focus their study on whether reducing parental stress would change how well children stuck to taking their asthma medications. However, that focus quickly changed, says Shelef. “Medication adherence just wasn’t a meaningful goal to most parents,” she explains. “To them, having more symptom-free days was a better gauge of how well an intervention was working for their children.”
The proposed intervention itself also transformed. Rather than focusing on problem-solving, cognitive-reframing and parenting skills — the researchers’ initial ideas — the final intervention would instead teach participants mindfulness, deep breathing, positive thinking, self-care and gratitude — as well as how to use these coping skills with their children. Rather than being staffed by social workers or psychologists, the stakeholders preferred people they felt they could relate to: Community wellness coaches with experience teaching yoga, meditation or other wellness activities in neighborhoods in which they lived.
Several other tweaks significantly changed the study from its early incarnation into the final version that the researchers are currently implementing, says Dr. Teach. “We ended up in a very different place from where we started based on this extensive process of stakeholder engagement,” he says.
Shelef notes that it’s not always feasible to involve stakeholders so heavily or to intensively plan a study for a year before it begins. Keeping all the advisers focused on the study at hand without radically changing the focus was a challenge, she says, and it was an “incredible scramble” in the end to translate all of their feedback into a cohesive product. However, having input from the people who could gain the most from the research results made it all worth it.
“The real benefit to this approach is the richness of the final product,” Shelef says. “Ultimately, this study will show a lot more than if we hadn’t put so much into it at the beginning.”
Asthma is an exceedingly common pediatric disease, affecting nearly 7 million children in the United States, particularly in urban areas. Asthma is responsible for more than 775,000 Emergency Department (EDs) visits each year. However, the vast majority of these visits are to community EDs closest to patients’ homes, rather than to medical centers that specialize in pediatric care.
This fact could potentially lead to big problems for small patients, says Theresa A. Walls, M.D., M.P.H., Director of Emergency Department Outreach at Children’s National Health System. Nearly 70 percent of EDs in the United States treat fewer than 14 children a day, leaving many without the requisite experience or resources critical to effectively treat pediatric patients. Research shows that children seen for asthma in general community EDs are less likely to receive corticosteroid medications systemically — an essential first-line therapy during an asthma attack per National Institutes of Health guidelines — compared with children seen at pediatric EDs. Additionally in these general EDs, children are also more likely to receive unnecessary testing and treatment.
“In our experience, the emergency care of children with asthma in our area mirrors what has been found in national studies: Children are not treated as aggressively in community EDs. If we partner with them and get them to treat asthma as aggressively as we do, it would be a great thing for pediatric patients.”
That’s why when a nurse educator from a local community hospital’s ED contacted them to try to improve pediatric asthma care, Dr. Walls and Children’s colleagues jumped at the opportunity. “They were motivated participants,” she says. “It was a great way to start a partnership.”
The team worked with the community hospital’s ED to implement a pediatric asthma care plan known as a “pathway,” similar to the one currently in place at Children’s National, to ensure that children in the throes of an asthma attack receive evidence-based care that significantly decreases their chances of hospital admission or transfer to a specialty center.
The treatment pathway includes elements such as assigning each patient an asthma score — a number ranging from 1 to 10 that characterizes the severity of the patient’s asthma attack. The treatment plan also includes providing corticosteroids as quickly as possible to more eligible patients.
Effectively implementing this plan requires the efforts of a multidisciplinary team of providers and experts. Beyond the physicians, nurses and respiratory therapists who care for patients directly, this includes pharmacists to ensure proper doses of medications are available in child-friendly liquid forms and information technology specialists to revamp the hospital’s electronic charting system, automatically requesting an asthma score or recommending appropriate medication orders.
To gauge whether mimicking Children’s asthma pathway made a significant difference at the community ED, Dr. Walls and colleagues launched a study that was published online December 8, 2016, in Pediatrics. Comparing data collected for 19 months after the new guidelines were put into place with data from 12 months prior, the researchers made some promising initial findings. Following the pathway implementation, 64 percent of children ages 2 to 17 who arrived at the community ED with asthma symptoms received an asthma score. About 76 percent of these patients with asthma received corticosteroids after the pathway was in place, compared with 60 percent of comparable patients prior to the switchover. The mean time to corticosteroid administration dropped by nearly half, falling from 196 to 105 minutes. Additionally, Dr. Walls says, 10 percent of patients required transfer to another hospital after pathway implementation, compared with 14 percent before — another significant drop.
Dr. Walls notes that there is significant room for improving these metrics and overall asthma care at community EDs. The research team hopes to continue working with the first community hospital and expand their partnership to form a network of other local hospitals. By working together in a large collaboration, she says, hospitals can share resources and knowledge while learning from each other’s successes and mistakes.
“The more we can deliver this state-of-the-art care to the community,” she says, “the better, because that’s where most kids go.”
According to the Centers for Disease Control and Prevention, 8.6 percent of children across the nation, or 6.3 million kids, have asthma, a disease characterized by wheezing and coughing associated with airway obstruction, bronchial hyperresponsiveness, and inflammation of the airway. However, children with asthma with low socioeconomic status who live in inner cities experience a disproportionately high burden of illness. While treatment guidelines provide uniformity in managing allergy and allergic inflammation, such approaches may be misdirected when kids have asthma symptoms but lack allergy or allergic inflammation. Knowledge of distinct disease phenotypes can help to improve care.
The Asthma Phenotypes in the Inner City study enrolled school-aged kids living in nine U.S. inner cities, including Washington, DC. The research team collected data about their asthma at the beginning of the one-year study and every two months as the kids’ asthma was managed according to accepted guidelines. Phenotypic analysis for 616 of these kids found their asthma clustered into five distinct groups. Cluster “A” was characterized by lower allergy, lower inflammation, and minimal symptoms. Fifteen percent of the kids fit within “A.” Another 15 percent of kids’ asthma fit within Cluster “B.” They had highly symptomatic asthma despite high step-level treatment and relatively low allergy and inflammation. Cluster “C” was distinguished by minimal symptoms, intermediate allergy and inflammation, and mildly impaired pulmonary physiology. Some 24 percent of kids fit within this group. The remaining kids fit within Cluster “D” or “E” and experienced progressively higher asthma and rhinitis symptoms as well as allergy and inflammation.
Questions for future research
Q: How does exposure to allergens, viruses, and irritants like tobacco smoke—taken individually as well as in combination—influence asthma severity and symptoms for these at-risk youths?
For the small number of U.S. children who grow up on working farms, activities such as feeding the cows and clearing spent hay from the barn are little changed from a thousand years ago. Through such close contact with dirt and farm animals, rural kids’ immune systems develop more normally and better distinguish common bacteria from household allergens like dust, molds, pets, and pests. Rates of allergy and asthma continue to be lower in children who grow up in those conditions.
By contrast, rates of asthma have spiked among urban and disadvantaged kids, who have far less exposure to dirt and animals early in life. Today, leading pediatric institutions, such as Children’s National Health System, are “awash in emergency department (ED) visits for asthma” with each ED visit associated with 10 to 15 missed school days annually on a population basis, says Stephen J. Teach, MD, MPH, Director and Principal Investigator of IMPACT DC , a care, research, and advocacy program focused on under-resourced and largely minority children with asthma.
A paradigm-shifting multicenter clinical trial aims to reverse that trend by going old school and safely exposing very young infants to the type of immune system training they would have experienced if they grew up closer to the earth.
The five-year study, named “Oral Bacterial Extracts (ORBEX): Primary Prevention of Asthma and Wheezing in Children,” is funded by a $27 million cooperative agreement grant from the National Heart, Lung, and Blood Institute, which is part of the National Institutes of Health. Children’s National, one of eight participating sites across the nation, will enroll an estimated 150 children in the study and will receive at least $2.5 million of that grant.
“It is currently thought by many, including me, that asthma and allergic diseases are a result of disordered development of the immune system very early in life,” says Dr. Teach, who is also Chair of the Department of Pediatrics at George Washington University. The immune system development process begins to unfold in the last few months of pregnancy and continues through infancy, meaning “the die is cast, we think, at a very young age.”
According to the Centers for Disease Control and Prevention, 8.6 percent of children across the nation have asthma, but in the District of Columbia, a disproportionately higher number of children suffer from the respiratory ailment. Once children experience early wheezing, changes begin to occur in the architecture of their lungs, causing a thicker basement membrane, a thickening of the lining of the lungs, and resulting in a heightened tendency for the airways in the lungs to become inflamed and to excrete more mucous. As a result, the children’s poorly trained immune system becomes hyper vigilant, ready to recognize a multitude of things as potentially allergenic.
“We’ve got to do something to change the course of the disease and to make it less common and less severe,” Dr. Teach says.
The study will identify 1,000 babies who range in age from 6 months to 18 months who are the highest risk for asthma, either through family history, being diagnosed with eczema, or both. The infants will receive safe doses of the inactivated bacteria, which is marketed under the name Broncho-Vaxom®. The therapy comes in capsule form, which for two years will be sprinkled into bottles or onto food. The children will be followed to gauge whether infants randomly assigned to receive treatment suffer fewer respiratory symptoms than infants randomly assigned to receive placebo.
“The rationale if we can expose these very young children to the benefits, but not the risks, of early life bacterial exposure, they may reap the benefits of developing a more properly functioning and less allergic immune system,” Dr. Teach says.
He says the Children’s National research team has had “remarkable success” engaging young children and their parents in such long-term studies, losing few to attrition.
“Going for five years will be breaking new ground. But all of our experience suggests that we will succeed if we show the families we care, we stay in touch with them, and we form these therapeutic partnerships by saying: ‘We want to partner with you. We can do this safely with mutual benefit.’ Families will get on board,” he says.
Once children experience early wheezing, changes begin in the architecture of their lungs, causing a thicker basement membrane, a thickening of the lining of the lungs, which can result in a heightened tendency for the airways in the lungs to become inflamed.
Enroll in this clinical trial—https://clinicaltrials.gov/ct2/show/NCT02148796
June 16, 2016 – Increased identification of the primary care provider as the main source of asthma care among urban minority children
The research team used electronic communication between an asthma specialty clinic and short-term care coordination to encourage parents of urban youth with asthma to identify their primary care provider as the key source for episodic asthma care – rather than the emergency department. Guardians of 50 children were enrolled in the prospective cohort study, whose findings were published in Journal of Asthma. The youths’ median age was 5.8 years; 64 percent were male, 98 percent were African American. At three and six months after the intervention, 85 percent and 83 percent, respectively, reported that the primary care provider was their child’s primary asthma healthcare provider, compared with 70 percent at baseline.
June 16, 2016 – Two sampling methods yield distinct microbial signatures in the nasopharynges of asthmatic children
The nasopharynx acts as an anatomical reservoir from which pathogenic microbes spread to the lower and upper respiratory airways, causing respiratory infections. A team led by Children’s National researchers used targeted 16S rRNA MiSeq sequencing and two techniques – nasal washes and nasal brushes – to characterize the nasopharyngeal microbiota in 30 children with asthma aged 6 to 17. The authors report in Microbiome that the children’s nasopharyngeal microenvironments contain microbiotas with different diversity and structure.
Nov. 30, 2015 – Alex’s Lemonade Stand Foundation grant to develop immune-based therapy
Physician-scientist Conrad Russell Y. Cruz, MD, PhD, was awarded a $450,000, grant from the Alex’s Lemonade Stand Foundation to develop novel cell-based therapies to combat pediatric cancer. The “A” grant encourages scientists to develop innovative treatments and cures that impact children with cancer and will provide Dr. Cruz and his team funding for three years.