Pulmonology and Sleep Medicine News

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?”

little boy using asthma inhaler

Asthma is associated with severe obstructive sleep apnea in children

little boy using asthma inhaler

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.

cars in traffic

Sleep science: Decoding drowsy driving

cars in traffic

A study published in The Journal of Pediatrics finds an association between a teen’s preference for evening or morning activities, coupled with nightly sleep duration, influences how awake they feel behind the wheel.

Each year, around Daylight Saving Time, we set our clocks forward and reprogram our bodies to adjust to spring. While most people welcome warmer days and lingering daylight, the time transition – and losing an hour of sleep – may leave some feeling jet lag.

For teens, the time transition is even more pronounced. Due to an adolescent’s developing body and a release of hormones to support growth and development, their biological clock is naturally set for late-evening bedtimes. Getting enough sleep is tough, especially with packed activity schedules and early-morning school start times.

A new study in The Journal of Pediatrics finds the impact of student sleep deprivation extends past feeling alert in class. Almost half of teen drivers surveyed – 205 out of 431 – from Fairfax County Public Schools reported driving drowsy at least once during the 2015 school year, the study period. Out of the 431-person sample, 63.1 percent of respondents reported driving several times a week. One-third of participants drove every day.

Helping teens feel alert behind the wheel is two-fold: Healthy school start times, those starting at 8:30 a.m. or later, help. Getting enough sleep is critical. The researchers also found that a student’s chronotype, or their preference for morning or evening activities, based on the Morningness-Eveningness Scale for Children, factor into drowsy driving:

  • Students with an evening chronotype, or preference for evening activities, coupled with shorter school-night sleep duration, were more likely to experience sleep-impaired driving.
  • Students with a morning chronotype, and who got at least eight hours of sleep, had the lowest prevalence of drowsy driving.
  • Compared with students who slept for at least eight hours on school nights, those who slept for less than seven hours had a 13.9 percent higher prevalence of drowsy driving.
  • The mean age of students surveyed was 16.9 years. The mean range of school-night sleep was seven hours.

Daniel Lewin, Ph.D., associate director of sleep medicine at Children’s National Health System, encourages schools to adopt later school start times, which Fairfax County Public Schools did, and he encourages students and families to assess their sleep patterns – focusing not just on sleep quantity but on sleep quality. His advice for families or students hesitant to change is to start small.

Try a seven-day challenge: Sleep on a regular schedule, sleep for recommended amounts of time, based on age-appropriate guidelines, cut out naps and eliminate late-afternoon caffeine intake.

Most children and families will start to notice the immediate benefits of getting a good night’s sleep, especially throughout the week: less daytime sleepiness, happier moods, improved eating habits and feeling more alert behind the wheel, which impacts driver safety – and not just for teen drivers but for parents, teachers and everyone on the road.

Robin Steinhorn in the NICU

Coming together as a team for the good of the baby

Robin Steinhorn in the NICU

Children’s National has a new program to care for children who have severe bronchopulmonary dysplasia, a serious complication of preterm birth.

Around the 1-year-old’s crib is a tight circle of smiling adults, and at the foot of his bed is a menagerie of plush animals, each a different color and texture and shape to spark his curiosity and sharpen his intellect.

Gone are the days a newborn with extremely complex medical needs like Elijah would transfer from the neonatal intensive care unit (NICU) to the pediatric intensive care unit and transition through a couple of other hospital units by the time he was discharged. Gone are the days when he’d see a variety of new physician faces at every stop. And gone are the days he’d be confined to his room, divorced from the sights and sounds and scents of the outside world, stimulation that helps little baby’s neural networks grow stronger.

Children’s National has a new program designed to meet the unique needs of children like Elijah who have severe bronchopulmonary dysplasia (BPD), a common complication of preterm birth.

“It’s more forward-thinking – and I mean thinking for the future of each individual baby, and it’s allowing the baby to have one team and one location to take advantage of a deep knowledge of and relationship with that baby and family,” says Robin Steinhorn, M.D. Dr. Steinhorn is senior vice president of the Center for Hospital-Based Specialties and one of Children’s multidisciplinary team members who visited Elijah’s bed twice weekly during his lengthy hospitalization and who continues to see him regularly during outpatient visits.

“The pulmonologist, the neonatologist, the respiratory therapist, the physical therapist, the dietitian, the cardiologist – we all come as a team to work together for the good of the baby,” Dr. Steinhorn adds. “We stick with these babies through thick and thin. We will stick with that baby with this team and this location until they are ready to go home – and beyond.”

BPD, a serious lung condition, mostly affects extremely low birthweight preterm babies whose lungs were designed to continue developing inside the womb until the pregnancy reaches full term. Often born months before their due dates, these extremely vulnerable newborns have immature organs, including the lungs, which are not ready for the task of breathing air. Children’s program targets infants who experience respiratory failure from BPD. The respiratory support required for these infants ranges from oxygen delivered through a nasal cannula to mechanical ventilators.

Robin Steinhorn and Colleague

“It’s more forward-thinking – and I mean thinking for the future of each individual baby, and it’s allowing the baby to have one team and one location to take advantage of a deep knowledge of and relationship with that baby and family,” says Robin Steinhorn, M.D.

About 1 percent of all preterm births are extremely low birthweight, or less than 1,500 grams. Within that group, up to 40 percent will develop BPD. While they represent a small percentage of overall births, these very sick babies need comprehensive, focused care for the first few years of their lives. And some infants with severe BPD also have pulmonary hypertension which, at Children’s National, is co-managed by cardiology and pulmonary specialists.

Children’s BPD team not only focuses on the child’s survival and medical care, they focus on the neurodevelopmental and social care that a baby needs to thrive. From enhanced nutrition to occupational and physical therapy to a regular sleep cycle, the goal is to help these babies achieve their full potential.

“These babies are at tremendous risk for long-term developmental issues. Everything we do is geared to alleviate that,” adds John T. Berger III, M.D., director of Children’s Pulmonary Hypertension Program.

“Our NICU care is more focused, comprehensive and consistent,” agrees Mariam Said, M.D., a neonatologist on the team. “We’re also optimizing the timing of care and diagnostic testing that will directly impact health outcomes.”

Leaving no detail overlooked, the team also ensures that infants have age-appropriate developmental stimuli, like toys, and push for early mobility by getting children up and out of bed and into a chair or riding in a wagon.

“The standard approach is to keep the baby in a room with limited physical or occupational therapy and a lack of appropriate stimulation,” says Geovanny Perez, M.D., a pulmonologist on the team. “A normal baby interacts with their environment inside the home and outside the home. We aim to mimic that within the hospital environment.”

Dr. Steinhorn, who had long dreamed of creating this comprehensive team care approach adds that “it’s been so gratifying to see it adopted and embraced so quickly by Children’s NICU caregivers.”

Teenage boy sleeping

Longer concussion recovery in children connected to poor sleep

Teenage boy sleeping

A new research study suggests that adolescents who get a good night’s sleep after a sports-related concussion might be linked to a shorter recovery time.

Research presented at the American Academy of Pediatrics Conference in Orlando, Fla., concluded that young athletes who slept well after a concussion were more likely to recover within two weeks, while those that didn’t receive a good night’s rest increased their likelihood to endure symptoms for 30 days or more.

The design and method was observational, where sleep factors and recovery are examined in association with each other. While the design does not allow a strong causal relationship to be established, it does not report control of other possible mediating variables, its sample size and strength of the findings are strongly suggestive, and provide a rationale for further study of sleep as a critical factor in recovery.

According to Gerard Gioia, Ph.D., chief of the Division of Pediatric Neuropsychology at Children’s National Health System, clinicians should ensure that sleep is properly assessed post-concussion and appropriate sleep hygiene strategies should be provided to the patient and family.

The average age of the 356 participants in the study was 14. Researchers conducting the study had the participants complete a questionnaire called the Pittsburgh Sleep Quality Index. Based on the answers reported, the teens were grouped into two categories: 261 good sleepers and 95 poor sleepers.

“The study highlights the importance of sleep, a critical factor in the recovery from a concussion,” says Dr. Gioia, “These findings are highly consistent with our own clinical experience in treating children and adolescents with concussions in that poor sleep are a significant limiting factor in recovery.”

During the follow-up visits three months later, both groups of patients had improved, however the good sleepers continued to have significantly better symptoms and sleep scores.

Anastassios Koumbourlis

Challenging the diagnostic criteria for pediatric asthma

Anastassios Koumbourlis

Recent research by Anastassios Koumbourlis, M.D., M.P.H, and colleagues challenges the use of the term physician-diagnosed asthma (PDA).

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.

AlgometRX

Breakthrough device objectively measures pain type, intensity and drug effects

AlgometRX

Clinical Research Assistant Kevin Jackson uses AlgometRx Platform Technology on Sarah Taylor’s eyes to measure her degree of pain. Children’s National Medical Center is testing an experimental device that aims to measure pain according to how pupils react to certain stimuli. (AP Photo/Manuel Balce Ceneta)

Pediatric anesthesiologist Julia C. Finkel, M.D., of Children’s National Health System, gazed into the eyes of a newborn patient determined to find a better way to measure the effectiveness of pain treatment on one so tiny and unable to verbalize. Then she realized the answer was staring back at her.

Armed with the knowledge that pain and analgesic drugs produce an involuntary response from the pupil, Dr. Finkel developed AlgometRx, a first-of-its-kind handheld device that measures a patient’s pupillary response and, using proprietary algorithms, provides a diagnostic measurement of pain intensity, pain type and, after treatment is administered, monitors efficacy. Her initial goal was to improve the care of premature infants. She now has a device that can be used with children of any age and adults.

“Pain is very complex and it is currently the only vital sign that is not objectively measured,” says Dr. Finkel, who has more than 25 years of experience as a pain specialist. “The systematic problem we are facing today is that healthcare providers prescribe pain medicine based on subjective self-reporting, which can often be inaccurate, rather than based on an objective measure of pain type and intensity.” To illustrate her point, Dr. Finkel continues, “A clinician would never prescribe blood pressure medicine without first taking a patient’s blood pressure.”

The current standard of care for measuring pain is the 0-to-10 pain scale, which is based on subjective, observational and self-reporting techniques. Patients indicate their level of pain, with zero being no pain and ten being highest or most severe pain. This subjective system increases the likelihood of inaccuracy, with the problem being most acute with pediatric and non-verbal patients. Moreover, Dr. Finkel points out that subjective pain scores cannot be standardized, heightening the potential for misdiagnosis, over-treatment or under-treatment.

Dr. Finkel, who serves as director of Research and Development for Pain Medicine at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, says that a key step in addressing the opioid crisis is providing physicians with objective, real-time data on a patient’s pain level and type, to safely prescribe the right drug and dosage or an alternate treatment.,

She notes that opioids are prescribed for patients who report high pain scores and are sometimes prescribed in cases where they are not appropriate. Dr. Finkel points to the example of sciatica, a neuropathic pain sensation felt in the lower back, legs and buttocks. Sciatica pain is carried by touch fibers that do not have opioid receptors, which makes opioids an inappropriate choice for treating that type of pain.

A pain biomarker could rapidly advance both clinical practice and pain research, Dr. Finkel adds. For clinicians, the power to identify the type and magnitude of a patient’s nociception (detection of pain stimuli) would provide a much-needed scientific foundation for approaching pain treatment. Nociception could be monitored through the course of treatment so that dosing is targeted and personalized to ensure patients receive adequate pain relief while reducing side effects.

“A validated measure to show whether or not an opioid is indicated for a given patient could ease the health care system’s transition from overreliance on opioids to a more comprehensive and less harmful approach to pain management,” says Dr. Finkel.

She also notes that objective pain measurement can provide much needed help in validating complementary approaches to pain management, such as acupuncture, physical therapy, virtual reality and other non-pharmacological interventions.

Dr. Finkel’s technology, called AlgometRx, has been selected by the U.S. Food and Drug Administration (FDA) to participate in its “Innovation Challenge: Devices to Prevent and Treat Opioid Use Disorder.” She is also the recipient of Small Business Innovation Research (SBIR) grant from the National Institute on Drug Abuse.

general school supplies

Studying the impact of later school start times

general school supplies

Teens have a biological preference to fall asleep later than younger children and adults, and wake up later, due to a delayed release of hormones that promote sleep. This timing coincides with puberty and makes it harder for middle and high school students to fall asleep early – regardless of 5 a.m. alarms and 7:17 a.m. school start times.

After studying this trend among nearly 1,000 seventh and eighth-grade students in 11 middle schools within a Mid-Atlantic school district, Daniel Lewin, Ph.D., a sleep medicine specialist, pediatric psychologist and associate director of the sleep medicine program at Children’s National Health System, coauthored and published research entitled “Later Start, Longer Sleep: Implications of Middle School Start Times” in the Journal of School Health, which outlines the benefits of delaying school start times.

The research team divided students into two groups: Close to 650 students attended eight late-starting middle schools, where school started at 8 a.m., while nearly 350 students attended early-starting middle schools, where school started at 7:23 a.m.

Students starting school 37 minutes later, despite going to bed 15 minutes later than peers attending an earlier-starting school, got 17 minutes more sleep each night and were more likely to report feeling wide awake during class. The researchers predicted this later-starting school model would translate to students getting an extra 75 minutes of sleep a week – roughly 51 hours of extra sleep each school year. These researchers find that every two minutes in delayed school start times results in one minute of additional sleep each night for children and teens.

Sleep Chart

Middle and high school students should get 8.5 to 10.5 hours of sleep each night, ideally between 9 p.m. and 8:30 a.m. for 12- to 15-year-olds and 10:30 p.m. and 9 a.m. for 16- to 18-year-olds.

The American Academy of Pediatrics (AAP) published similar research in their journal, Pediatrics, about the benefits of letting teens catch up on sleep, citing a reduced risk of students being overweight, getting into car accidents or suffering from depression as well as a greater likelihood of having better grades, higher test scores and a better quality of life. AAP recommends schools start at 8:30 a.m. or later to allow students to get 8.5 to 9.5 hours of sleep each night and issued a statement in 2014, entitled “School Start Times for Adolescents.”

Dr. Lewin continues to track these benefits and works with schools to implement the changes. He recently wrote an editorial, entitled “All the Clocks Are Ticking: Sleep Health and Metabolism,” for the Journal of Adolescent Health about the correlation between improved sleep health, mental and physical health and academic performance, explaining how circadian clocks, present on a cellular level, influence behavior and metabolism.

While pushing school start times back requires an immediate investment of rearranging travel routes, bell schedules and after-school activities, several school districts near Washington, D.C., from Virginia Beach to Fairfax County, are adopting this public health model.

An economic analysis conducted by the RAND Corporation finds that after two years, the benefits of reorganizing school start times outweigh the costs.

Young girl sleeping

Is actigraphy helpful for assessing sleep-wake disorders?

Young girl sleeping

The second most-read article in 2018 in the Journal of Clinical Sleep Medicine, published by the American Academy of Sleep Medicine (AASM), was about using actigraphy to evaluate sleep disorders and circadian rhythm sleep-wake disorders.

FDA-approved actigraphy devices are typically kept on the wrist or ankle and track movement activity, which researchers can use as part of a larger toolset to analyze how much activity occurs right before and during sleep.

The AASM guidelines, entitled “Use of Actigraphy for the Evaluation of Sleep Disorders and Circadian Rhythm Sleep-Wake Disorders: An American Academy of Sleep Medicine Clinical Practice Guideline,” included the AASM’s stance on clinical recommendations for children and adults, rated as strong or conditional.

The conditions for evaluating pediatric health conditions are as follows:

  1. The AASM suggests that clinicians use actigraphy in the assessment of pediatric patients with insomnia disorder. (Conditional)
  2. The AASM suggests that clinicians use actigraphy in the assessment of pediatric patients with circadian rhythm sleep-wake disorder. (Conditional)
  3. The AASM suggests that clinicians use actigraphy to monitor total sleep time prior to testing with the Multiple Sleep Latency Test in adult and pediatric patients with suspected central disorders of hypersomnolence. (Conditional)
  4. The AASM recommends that clinicians not use actigraphy in place of electromyography for the diagnosis of periodic limb movement disorder in adult and pediatric patients. (Strong)

In an interview with Neurology Today, Daniel Lewin, Ph.D., a sleep medicine specialist, pediatric psychologist and associate director of the sleep medicine program at Children’s National Health System, offered advice, alongside other sleep medicine experts, about the new guidelines:

“It’s a very powerful tool, but it does require some knowledge of basic sleep mechanisms and of how the tool can be used and what variables can be extracted from the tool,” Dr. Lewin said in the interview with Susan Kreimer.

Anne Goldstein, M.D., M.S., assistant professor of neurology at the University of Michigan Sleep Disorders Center, tells Kreimer that “Actigraphy records only movement and that non-moving is often misinterpreted as sleep.”

Dr. Lewin has used actigraphy in sleep research studies but notes the use of these devices come with extensive training. Other researchers expressed similar sentiments with Neurology Today, noting the value of the sleep assessment tool to capture preliminary sleep behavior assessments, similar to a self-reported sleep log, while noting their limitations, such as capturing sleep patterns over extended periods of time, instead of in 14-day increments.

“When you’re living a typical active human life, sleep can wax and wane, depending on travel patterns, work responsibilities and stress levels,” Nathaniel F. Watson, M.D., professor of neurology at the University of Washington School of Medicine in Seattle and director of the UW Medicine Sleep Clinic, tells Kreimer. “This variability in sleep highlights the need for additional technologies capable of assessing sleep over longer periods of time.”

Read about other researcher’s perspectives captured by Susan Kreimer for Neurology Today.

smiling baby sleeping

The science behind optimal sleep health

smiling baby sleeping

Children younger than age 2 need at least 12 hours of sleep each day.

As families and parents renew their interest in health in the new year, pediatricians can take advantage of this momentum by talking about one area absent from common New Year’s resolutions lists: getting enough sleep.

Like diet, exercise and activities that keep your brain sharp, such as reading or learning a new language, healthful sleep patterns play a vital role in supporting physical health and cognitive performance – especially for children and teens.

Here are a few tips parents and pediatricians can use, based on research published by Daniel Lewin, Ph.D., a pediatric psychologist and sleep medicine specialist at Children’s National Health System.

Understand how much sleep each child needs.

The typical range of recommended sleep, such as eight to 10 hours each night, varies for each child. A 16-year-old may do well with 8.5 hours of sleep, while a 6-year-old may need 13 hours of sleep to stay alert. Their body is still rapidly developing. The timing of sleep matters, too, due to a child’s natural circadian rhythm. A chart below details sleep recommendations based on age.

Sleep Chart

Turn a child’s bedroom into a healthful sleep chamber.

Encouraging children to fall asleep by 7 or 9 p.m. may require planning – outside of maintaining regular sleep schedules. To start, make it easy to promote sound sleep by eliminating distractions, including clocks and electronic devices, which might sit next to a child’s bed and distract him or her from getting a good night’s sleep.

Reserve a designated area for homework and study hours outside of the bedroom, which helps reinforce that the bed is a place for sleep and rest. Avoid doing any complicated routines or activities that might cause excitement right before bed, such as assembling a new toy or playing a high-stakes game.

Follow the same rules for conversations: Don’t have talks that might evoke excitement, like the next Disneyworld vacation, or stress, such as bringing the next day’s spelling test up right before bed. By creating a calm zone, you’ll avoid energizing the biological ‘burst zone,’ a rush of energy that occurs in short bursts before one prepares to rest for the night. Keep conversations and routines simple and soothing. Reading, stretching or practicing mindfulness and yoga are complementary activities children can practice at least 15 minutes before bedtime.

Schedule activities about circadian rhythms.

Understanding when a child sleeps best is just as important as understanding how much sleep is essential to support optimal health. A student in high school is biologically wired to stay up past 9 p.m. due to a later release of hormones that promote sleep. This is one reason some school systems are experimenting with later middle and high school start times, which, according to a review in the Journal of School Health, increases a student’s chance of feeling ‘wide awake’ and alert in the classroom.

If you have control of your student’s schedule, plan around it. For instance, schedule activities for a 17-year-old in the late morning, if possible, while allowing time in the afternoon for a young child to take a nap.

These starter tips serve as ways to strengthen sleep quality. Learn more about Dr. Lewin’s research at PubMed, view a few of his blogs for parents at U.S. News & World Report and learn about the link between sleep and health at the National Institutes of Health. If you experience recurring problems, such as sleep apnea, insomnia, sleep walking, ongoing sleep disruptions or excessive daytime sleepiness, connect with a health care provider.

Staphylococcus aureus

Understanding antibiotic resistance in patients with cystic fibrosis

Staphylococcus aureus

Patients with cystic fibrosis who carried antibiotic-resistant bacteria, such as Staphylococcus aureus, in their lungs had significantly lower microbial diversity and more aggressive disease, according to a small study published in Heliyon.

A defective gene causes thick, sticky mucus to build up in the lungs of patients with cystic fibrosis (CF). There, it traps bacteria, causing patients to develop frequent lung infections that progressively damage these vital organs and impair patients’ ability to breathe.

Most patients with this progressive genetic disorder die by the fourth decade of life. A key to helping patients live even that long – a vast improvement from an average lifespan of 10 years  just decades ago – is judicious use of antibiotics, explains Andrea Hahn, M.D., a pediatric infectious diseases specialist at Children’s National Health System.

But antibiotics are a double-edged sword, Dr. Hahn adds: Although they’re necessary to eradicate lung infections, repeated use of these drugs can lead to antibiotic resistance, making it tougher to treat future infections. Also, antibiotic use can kill the nonpathogenic bacteria living in the lungs as well. That decreases the diversity of the microbial community that resides in the lungs, a factor associated with disease progression. But how antibiotic resistance impacts the relationship between lung bacterial diversity and CF patients’ pulmonary function has been unknown.

Dr. Hahn and colleagues investigated this question in a small study that was published online Sept. 17, 2018, in Heliyon. Their findings suggest that the presence of multidrug resistant bacteria in the airways of patients with CF is associated with decreased microbial diversity and decreased pulmonary function.

In the study, the researchers recruited six patients with CF from Children’s National during well-child visits. During those appointments, the research team collected respiratory secretions from these volunteers. They collected more samples at subsequent visits, including:

  • When patients were admitted to the hospital for pulmonary exacerbations (periods when infections inflamed their airways, making it difficult to breathe);
  • Just after intravenous antibiotic courses to treat these infections; and
  • Thirty days after patients completed antibiotic therapy, when their lungs’ bacterial flora had some time to bounce back.

Over the 18-month study period, these patients made multiple visits for exacerbations and antibiotic treatments, leading to samples from 19 patient encounters overall.

The scientists then analyzed each sample in two different ways. They used some to grow cultures in petri dishes, the classic method that labs use to figure out which bacterial species are present and to determine which antibiotics are effective in tamping them down. They used another part of the sample to run genetic analyses that searched for antibiotic resistance genes. Both methods were necessary to gather a complete inventory of which antibiotic-resistant bacteria were present, Dr. Hahn explains.

“Laboratory cultures are designed to grow certain types of bacteria that we know are problematic, but they don’t show everything,” she says. “By genetically sequencing these samples, we can see everything that’s there.”

Their results revealed a host of bacterial species present in these patients’ airways, including methicillin-resistant Staphylococcus aureus, a notoriously hard-to-treat microbe. Patients who carried this or other antibiotic-resistant bacteria had significantly lower microbial diversity in their samples and more aggressive disease. Their samples also were more likely to contain bacteria of the genus Alcaligenes, whose role in CF is not yet known.

Although heavy antibiotic use probably contributed to both the antibiotic resistance and lowered microbial diversity, Dr. Hahn says, the answer isn’t to reduce use of these drugs: They’re necessary to help patients with CF recover after each bout with pulmonary exacerbations. Rather, she says, using methods beyond a simple lab culture can help doctors target infectious bacteria more selectively, perhaps avoiding collateral damage.

“We can’t stop using antibiotics,” she says, “but we can learn to use them better.”

In addition to Dr. Hahn, Children’s co-authors include Aszia Burrell; Hani Fanous; Hollis Chaney, M.D.; Iman Sami Zakhari, M.D.; Geovanny F. Perez, M.D.; Anastassios C. Koumbourlis, M.D., MPH; and Robert J. Freishtat, M.D., MPH; and Senior Author, Keith A. Crandall, of The George Washington University.

Financial support for the research described in this post was provided by the National Institutes of Health National Center for Advancing Translational Sciences under award number UL1TR000075 and the National Heart, Lung and Blood Institute under award number K12HL119994.

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.

New treatment approach shows promise for patients with stage IV Wilms tumor

The study assessed the benefit of adding two additional chemotherapy agents, cyclophosphamide and etoposide, to the treatment regimen for patients with incomplete lung nodule response or tumor loss of heterozygosity (LOH) at chromosomes 1p and 16q, both associated with interior outcomes in previous studies.

Wilms tumor, which first develops in the kidneys, is the fifth most common cancer in children under 15 years old. While overall outcomes for patients with Wilms tumor are excellent, patients with metastatic disease, with the lung as the most common site of spread, fare worse than patients with localized disease. That’s why a new study showing significantly improved survival rates for patients with stage IV Wilms tumors with lung metastases is making waves in the pediatric oncology community.

The study, “Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children’s Oncology Group AREN0533 Study” – recently published in the Journal of Clinical Oncology with Jeffrey Dome, M.D., Ph.D., vice president for the Center for Cancer and Blood Disorders at Children’s National Health System, as the senior author – assessed whether lung radiation therapy, part of the standard treatment in combination with chemotherapy drugs, can be avoided for patients with complete lung nodule response after six weeks of chemotherapy. Conversely, the study assessed the benefit of adding two additional chemotherapy agents, cyclophosphamide and etoposide, to the treatment regimen for patients with incomplete lung nodule response or tumor loss of heterozygosity (LOH) at chromosomes 1p and 16q, both associated with interior outcomes in previous studies. The results show that:

  • The new approach to therapy resulted in a 4-year overall survival rate of 96 percent, compared to 84 percent on the predecessor study.
  • About 40 percent of patients with Wilms tumor and lung metastases can be spared initial upfront lung radiation and still have outstanding survival. This will decrease the long-term risk of heart toxicity and breast cancer.
  • Patients with incomplete lung nodule response after six weeks of therapy with cyclophosphamide and etoposide had significantly better 4-year event-free survival: 89 percent compared with 75 percent that was expected based on historical data.
  • Intensification of therapy for patients with LOH at 1p and 16q was highly effective: 4-year event-free survival rate improved from 66 percent on the previous study to 100 percent.

“These findings will change clinical practice and improve survival for patients with Wilms tumor whose cancer has spread to the lungs” said Dr. Dome. “The risk-adapted approach to treatment based on tumor biology and tumor response provides a framework for future studies as we come one step closer to achieving 100 percent survival without treatment-associated side effects.”

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.

Robin Steinhorn

Children’s National senior vice president elected to American Pediatric Society leadership

Robin Steinhorn

Robin Steinhorn, M.D., Senior Vice President of Center for Hospital-Based Specialties at Children’s National Health System, was elected by her peers to become vice president and president-elect of the American Pediatric Society (APS) beginning May 2018 at the annual Pediatric Societies Meeting in Toronto, Canada. Dr. Steinhorn will serve in this role for one year and will then become the Society’s president in May 2019 for a one-year term.

Dr. Steinhorn is a globally recognized physician-leader, researcher and clinician in the fields of neonatal perinatal medicine and fetal pulmonary development. She was elected to the APS Council in 2015 and currently holds a seat on the American Board of Pediatrics’ Board of Directors.

“Dr. Steinhorn has devoted her professional career to advancing the field of pediatrics through exemplary leadership in related societies, as well as editorial oversight of cutting-edge research,” says David Wessel, M.D., executive vice president and chief medical officer of Hospital and Specialty Services at Children’s National. “This elevated role with the APS will enable her to further share her expertise to benefit children on a national and international level.”

Dr. Steinhorn serves as associate editor of the Journal of Pediatrics and is also a contributing editor for NEJM Journal Watch’s Pediatric and Adolescent Medicine.  Additionally, she sits on the editorial boards of Pediatric Critical Care Medicine and Pulmonary Circulation. Dr. Steinhorn is an elected fellow of the American Heart Association and a member of both the Perinatal Research Society and the American Thorasic Society.

Founded in 1888, the American Pediatric Society is the oldest and most prestigious academic pediatric organization in North America. Members are elected to APS based on their accomplishments as academic leaders in pediatrics and goal to shape the future of academic pediatrics. Mark L. Batshaw, M.D., physician-in-chief and chief academic officer of Children’s National preceded Dr. Steinhorn as APS President from 2016-2017.

“This is a tremendous honor, and it is a special privilege to follow Dr. Batshaw’s sound leadership. I look forward to leveraging the collective leadership and research accomplishments by our members to improve the health of infants and children throughout the U.S.,” said Dr. Steinhorn.

Dr. Steinhorn joined Children’s National in 2015 after a successful tenure as professor and chair of the department of pediatrics at the University of California, Davis (UCD) School of Medicine and as physician-in-chief, UCD Children’s Hospital. Previously, she was vice chair of the department of pediatrics and chief of the division of neonatology at Northwestern University and the Ann & Robert H. Lurie Children’s Hospital of Chicago.

Dr. Steinhorn’s clinical and academic interests have focused primarily on fetal and neonatal pulmonary vascular development. Her translational work has spanned from in vitro studies, to experimental models and clinical trials. In addition to her own translational research program, she has participated in numerous multicenter trials that have helped define the clinical treatment of pulmonary hypertension during the neonatal period. Her clinical research work also has addressed other topics, such as harmonization of electronic health records for clinical research and telemedicine support of neonatal care in small rural hospitals.

Additionally, Dr. Steinhorn is particularly passionate about mentoring faculty and supporting the growth and career development of young neonatologists and scientists, with several having developed their own research laboratories and assumed division leadership positions. She was selected as a “Top Doctor” by Northern Virginia  Magazine in 2018.

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.

As pediatric use of iNO increased, mortality rates dropped

Smiling-baby-boy

iNO, a colorless odorless gas, is used to treat hypoxic respiratory failure in infants born full-term and near term.

Use of inhaled nitric oxide (iNO) among pediatric patients has increased since 2005 and, during a 10-year time period, mortality rates dropped modestly as the therapeutic approach was applied to a broader range of health ailments, according to an observational analysis presented Feb. 26, 2018, during the 47th Critical Care Congress.

iNO, a colorless odorless gas, is used to treat hypoxic respiratory failure in infants born full-term and near term and also has become an important therapy for acute respiratory distress syndrome and pulmonary hypertension in newborns.

Jonathan Chan, M.D., a Children’s National Health System critical care fellow, analyzed de-identified data from patient visits from January 2005 to December 2015 at 47 children’s hospitals around the nation. Dr. Chan included 18,343 patients in the analysis. Among the findings:

  • As a group, the children had an overall mortality rate of 22.7 percent. The mortality rate dropped from 29.1 percent in 2005 to 21.2 percent in 2015.
  • The median adjusted cost per admission was an estimated $158,740 ($5,846 per patient day).

“This large observational study indicates that the use of iNO grew from 2005 to 2015,” Dr. Chan says. “While hospital stays grew longer during the study period, we saw a decrease in mortality of 0.01 percent per year.”

The highest number of admissions with iNO use included:

Dr. Chan notes that because this is a retrospective observational analysis, the study’s findings should be interpreted as exploratory.

“Off-label use of iNO continues to increase among pediatric patients. And an increasing proportion of admissions are for specialty areas other than neonatal care,” he adds. “Increasing off-label use of iNO is associated with decreased mortality. But it also is associated with an increased length of stay, higher hospital costs and more units of iNO administered.”

47th Critical Care Congress presentation

Monday, Feb. 26, 2018

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.