Human Rhinovirus

Finding the root cause of bronchiolitis symptoms

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Human Rhinovirus

A new study shows that steroids might work for rhinovirus but not for respiratory syncytial virus.

Every winter, doctors’ offices and hospital emergency rooms fill with children who have bronchiolitis, an inflammation of the small airways in the lung. It’s responsible for about 130,000 admissions each year. Sometimes these young patients have symptoms reminiscent of a bad cold with a fever, cough and runny nose. Other times, bronchiolitis causes breathing troubles so severe that these children end up in the intensive care unit.

“The reality is that we don’t have anything to treat these patients aside from supportive care, such as intravenous fluids or respiratory support,” says Robert J. Freishtat, M.D., M.P.H., chief of emergency medicine at Children’s National Health System. “That’s really unacceptable because some kids get very, very sick.”

Several years ago, Dr. Freishtat says a clinical trial tested using steroids as a potential treatment for bronchiolitis. The thinking was that these drugs might reduce the inflammation that’s a hallmark of this condition. However, he says, the results weren’t a slam-dunk for steroids: The drugs didn’t seem to improve outcomes any better than a placebo.

But the trial had a critical flaw, he explains. Rather than having one homogenous cause, bronchiolitis is an umbrella term for a set of symptoms that can be caused by a number of different viruses. The most common ones are respiratory syncytial virus (RSV) and rhinovirus, the latter itself being an assortment of more than 100 different but related viruses. By treating bronchiolitis as a single disease, Dr. Freishtat says researchers might be ignoring the subtleties of each virus that influence whether a particular medication is useful.

“By treating all bronchiolitis patients with a single agent, we could be comparing apples with oranges,” he says. “The treatment may be completely different depending on the underlying cause.”

To test this idea, Dr. Freishtat and colleagues examined nasal secretions from 32 infants who had been hospitalized with bronchiolitis from 2011 to 2014 at 17 medical centers across the country that participate in a consortium called the 35th Multicenter Airway Research Collaboration. In half of these patients, lab tests confirmed that their bronchiolitis was caused by RSV; in the other half, the cause was rhinovirus.

From these nasal secretions, the researchers extracted nucleic acids called microRNAs. These molecules regulate the effects of different genes through a variety of different mechanisms, usually resulting in the effects of target genes being silenced. A single microRNA typically targets multiple genes by affecting messenger RNA, a molecule that’s key for producing proteins.

Comparing results between patients with RSV or rhinovirus, the researchers found 386 microRNAs that differed in concentration. Using bioinformatic software, they traced these microRNAs to thousands of messenger RNAs, looking for any interesting clues to important mechanisms of illness that might vary between the two viruses.

Their findings eventually turned up important differences between the two viruses in the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway, a protein cascade that’s intimately involved in the inflammatory response and is a target for many types of steroids. Rhinovirus appears to upregulate the expression of many members of this protein family, driving cells to make more of them, and downregulate inhibitors of this cascade. On the other hand, RSV didn’t seem to have much of an effect on this critical pathway.

To see if these effects translated into cells making more inflammatory molecules in this pathway, the researchers searched for various members of this protein cascade in the nasal secretions. They found an increase in two, known as RelA and NFkB2.

Based on these findings, published online Jan. 17, 2018, in Pediatric Research, steroids might work for rhinovirus but not for RSV, notes Dr. Freishtat the study’s senior author.

“We’re pretty close to saying that you’d need to conduct a clinical trial with respect to the virus, rather than the symptoms, to measure any effect from a given drug,” he says.

Future clinical trials might test the arsenal of currently available medicines to see if any has an effect on bronchiolitis caused by either of these two viruses. Further research into the mechanisms of each type of illness also might turn up new targets that researchers could develop new medicines to hit.

“Instead of determining the disease based on symptoms,” he says, “we can eventually treat the root cause.”

Study co-authors include Kohei Hasegawa, study lead author, and Carlos A. Camargo Jr., Massachusetts General Hospital; Marcos Pérez-Losada, The George Washington University School of Medicine and Health Sciences; Claire E. Hoptay, Samuel Epstein and Stephen J. Teach, M.D., M.P.H., Children’s National; Jonathan M. Mansbach, Boston Children’s Hospital; and Pedro A. Piedra, Baylor College of Medicine.

Omar-Ahmed

Child abuse prevention efforts should reach beyond parents

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Omar-Ahmed

The findings of a study performed by Omar Z. Ahmed, M.D., should prompt widening the net when attempting to prevent child abuse.

Non-accidental injuries of children by a parent are more common but are likely to be less severe than those caused by a parent’s male partner, a babysitter or a daycare worker, according to a Children’s National study presented during the 2017 American Academy of Pediatrics (AAP) national conference. Based on their findings, the researchers recommend that efforts to prevent child abuse be extended to these additional types of caregivers.

The study performed by Omar Z. Ahmed, M.D., retrospectively reviewed the records of children admitted from 2013 to 2015 to evaluate and treat non-accidental trauma and identified 225 cases of child abuse. The 150 cases for which the perpetrator was identified were included in their analyses. The research team performed multivariate analyses to determine the association between the gender of the alleged perpetrator, the perpetrator’s relationship to the child and the severity of the child’s injuries.

“Among the 150 children hospitalized after suffering non-accidental trauma during the study period, 68.4 percent were injured by a parent; 14 percent were injured by a stepparent, boyfriend or girlfriend; 9.7 percent were injured by a daycare staff member or babysitter; and 4.6 percent were injured by a relative,” says Dr. Ahmed, a research fellow in Children’s Division of Trauma and Burn Surgery. “By far, parents were more likely to be perpetrators of the confirmed or suspected child abuse. However, children injured by a parent’s partner – a group that was overwhelmingly male – were more likely to be more severely injured, to experience severe head injuries and were more likely to require intubation compared with children who were abused by a parent.”

The research team says that the findings should prompt widening the net when attempting to prevent child abuse.

“It confirmed a lot of what we already knew and what was suspected,” Dr. Ahmed says. ”By taking the research a step further – characterizing the severity of injuries and treatments provided within the hospital – we identified caregiver types who are associated with severe child abuse. It gives parents a warning as to what to look out for when children are cared for by other people in the child’s life.”

A next step for the research group: Pre-emptive approaches to target the caregiver groups more likely to place children at risk of injury, he adds. These strategies could include educating caregivers, teaching coping mechanisms and modeling behavior for a wider group of individuals caring for young children, such as how to manage children appropriately when things get difficult, rather than letting anger take over.

“Parents rely on daycare, babysitters and significant others to provide child care while they work; it is not realistic to expect that to change. But we can target these groups for behavior modification in order to decrease the risk of children being injured,” Dr. Ahmed adds.

group of teenagers sitting on a wall

Better PID management for adolescents in the ED

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group of teenagers sitting on a wall

Since adolescents account for half of all new sexually transmitted infection (STI) diagnoses, increasing screening rates for STIs in the emergency department could have a tremendous impact.

Emergency departments at U.S. children’s hospitals had low rates of complying with recommended HIV and syphilis screening for at-risk adolescents, though larger hospitals  were more likely to provide such evidence-based care, according to a study led by Monika Goyal, M.D., M.S.C.E., director of research in the Division of Emergency Medicine at Children’s National Health System.

Presented during the 2017 American Academy of Pediatrics (AAP) national conference, the study also found low compliance with CDC recommendations for antibiotic treatment of adolescents diagnosed with pelvic inflammatory disease (PID), a complication of undiagnosed or undertreated sexually transmitted infection that can signal heightened risk for syphilis or HIV.

“Adolescents account for half of all new sexually transmitted infections (STIs) and often view the emergency department (ED) as the primary place to receive health care. If we are able to increase screening rates for sexually transmitted infections in the ED setting, we could have a tremendous impact on the STI epidemic,” Dr. Goyal says.

Although gonorrhea and chlamydia are implicated in most cases of PID, The Centers for Disease Control and Prevention (CDC) recommend that all women diagnosed with PID be screened for HIV and also recommends syphilis screening for all people at high risk for infection. The research team conducted a cross-sectional study using a database that captures details from 48 children’s hospitals to determine how often the CDC’s recommendations are carried out within the nation’s EDs.

The research team combed through records from 2010 to 2015 to identify all ED visits by adolescent women younger than 21 and found 10,698 PID diagnoses. The girls’ mean age was 16.7. Nearly 54 percent were non-Latino black, and 37.8 percent ultimately were hospitalized.

“It is encouraging that testing for other sexually transmitted infections, such as gonorrhea and chlamydia, occurred for more than 80 percent of patients diagnosed with PID. Unfortunately, just 27.7 percent of these young women underwent syphilis screening, and only 22 percent were screened for HIV,” Dr. Goyal says.

premature baby in hospital incubator

Improving neonatal intubation training to boost clinical competency

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premature baby in hospital incubator

A research team from Children’s National Health System outlined gaps between current simulation training and clinical competency among pediatric residents and then shared recommendations to address them.

Redesigning the mannequins used in medical simulation training could improve residents’ readiness for clinical practice. Presenting at the 2017 American Academy of Pediatrics (AAP) national conference, a research team from Children’s National Health System outlined gaps between current simulation training and clinical competency among pediatric residents and then shared recommendations to address them.

The team noted that the transfer of skill from simulations to clinical encounters does not occur readily. They identified a number of differences between working with a training mannequin and caring for an actual infant: The mannequin’s tongue and head do not move naturally, no fluid lubricates its mouth and throat and, when tilting the head to insert the endotracheal tube, the mannequin’s neck does not flex realistically.

“Current mannequins lack physical and functional fidelity and those shortcomings take a toll on competency as pediatric residents transition from practice simulation sessions to the actual clinic,” says Children’s National Neonatologist Lamia Soghier, M.D., lead author of the poster presented during AAP. “Our work tried to tease out the most important differences between simulating neonatal intubation and actual clinical practice in order to ensure the next generation of mannequins and practice sessions translate to improved clinical competency.”

The study team conducted in-depth interviews with 32 members of the clinical staff, including attending neonatologists and second- and third-year fellows, asking about critical differences in environment, equipment and context as they participated in practice intubations as well as actual intubations in the clinic.

Four key themes emerged, Dr. Soghier and co-authors say:

  • Mannequins’ vocal cords are marked clearly in white, a give-away for trainees tasked with correctly identifying the anatomical feature. In addition, the mannequins are so stiff they need more force when practicing how to position them properly. In the NICU, using that much force could result in trauma.
  • Because current equipment does not simulate color change with a Pedi-Cap – a non-toxic chemical that changes color in response to exhaled carbon dioxide – trainees can develop poor habits.
  • Training scenarios need to be designed with the learner in mind offering an opportunity to master tasks in a step-by-step fashion, to practice appropriate sedation techniques and for beginners to learn first before being timed.
  • There is a marked mismatch between the feel of a simulated training and the electric urgency of performing the same procedure in the clinic, eroding trainees’ ability to adjust to wildcards in the clinic in real time.

“We carefully design our sessions to provide trainees with the suite of skills they will need to perform well in clinic. Still, there is more we can do inside the hospital and in designing the next generation of mannequins to lead to optimal clinical outcomes,” Dr. Soghier adds. “As a whole, mannequins need to more closely resemble an actual newborn, with flexible vocal cord design in natural colors. The mannequin’s neck should flex with more degrees of freedom. The model’s skin and joints also need to be more flexible, and its head and neck need to move more naturally.”

pill bottles and pills

White children more likely to receive unnecessary antibiotics in ED

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Although antibiotics can turn the tide for a variety of illnesses, they are ineffective against those caused by viruses. Despite this well-known fact, doctors often prescribe antibiotics for viral illnesses.

Infections now considered relatively easy to treat, including some forms of diarrhea and pneumonia, were the leading cause of death throughout the developed world until the 20th century. Then, scientists developed what eventually turned into a miracle cure: Antibiotics that could kill or thwart the growth of a broad array of bacterial species.

Although antibiotics can turn the tide for a variety of illnesses, they are ineffective against those caused by viruses. Despite this well-known fact, doctors often prescribe antibiotics for viral illnesses. Taking these drugs unnecessarily can fuel antibiotic resistance, giving rise to bacteria that don’t respond to the drugs that kept them in check in the past.

A new multicenter study shows how prevalent this scenario can be in hospitals’ Emergency Departments. This research, led by Monika K. Goyal, M.D., M.S.C.E., director of research in the Division of Emergency Medicine at Children’s National Health System, shows that non-Latino white children seeking treatment for viral infections in the Emergency Department (ED) are about twice as likely to receive an antibiotic unnecessarily compared with non-Latino black children or Latino children.

These findings, published online Sept. 5, 2017 in Pediatrics, echo similar racial and ethnic differences in treating acute respiratory tract infections in the primary care setting.

“It is encouraging that just 2.6 percent of children treated in pediatric EDs across the nation received antibiotics for viral acute respiratory tract infections since antibiotics are ineffective in treating viral infections,” Dr. Goyal says. “However, it is troubling to see such persistent racial and ethnic differences in how medications are prescribed, in this case in the ED. In addition to providing the best evidence-based care, we also strive to provide equitable care to all patients.”

Acute respiratory tract infections are among the most common reasons children are rushed to the ED for treatment, Dr. Goyal and co-authors write. Overprescribing antibiotics is also rampant for this viral ailment, with antibiotics erroneously prescribed for 13 percent to 75 percent of pediatric patients.

In the retrospective cohort study, the research team pored over deidentified electronic health data for the 2013 calendar year from seven geographically diverse pediatric EDs, capturing 39,445 encounters for these infections that met the study’s inclusion criteria. The patients’ mean age was 3.3 years old. Some 4.3 percent of non-Latino white patients received oral, intravenous or intramuscular antibiotics in the ED or upon discharge, compared with 2.6 percent of Latino patients and 1.9 percent of non-Latino black patients.

“A number of studies have demonstrated disparities with regards to how children of different ethnicities and races are treated in our nation’s pediatric EDs, including frequency of computed tomography scans for minor head trauma, laboratory and radiology tests and pain management. Unfortunately, today’s results provide further evidence of racial and ethnic differences in providing health care in the ED setting,” Dr. Goyal says. “Although, in this case, minority children received evidence-based care, more study is needed to explain why differences in care exist at all.”

At a time of growing antibiotic resistance, the study authors underscored the imperative to decrease excess antibiotic use in kids. Since the 1940s, the nation has relied on antibiotics to contend with diseases such as strep throat. Yet, according to the Centers for Disease Control and Prevention, at least 2 million people in the United States are infected with antibiotic-resistant bacteria each year.

According to the study authors, future research should explore the reasons that underlie racial and ethnic differences in antibiotic prescribing, including ED clinicians eager to appease anxious parents as well as implicit clinical bias. Dr. Goyal recently received a National Institutes of Health grant to further study racial and ethnic differences in how children seeking treatment at hospital EDs are managed.

“It may come down to factors as simple as providers or parents believing that ‘more is better,’ despite the clear public health risks of prescribing children antibiotics unnecessarily,” Dr. Goyal adds. “In this case, an intervention that educates parents and providers about appropriate antibiotic use could help the pediatric patients we care for today as well as in the future.”

Sabah IqbShilpa Patel, Monika Goyal

Stronger firearm laws reduce ED visits

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Sabah Iqbl, Shilpa Patel, Monika Goyal

Children’s National researchers Sabah F. Iqbal, M.D., Shilpa J. Patel, M.D., and Monika K. Goyal, M.D., M.S.C.E., found that regions of the United States with the strictest gun laws also have fewer emergency department visits for pediatric firearm-related injuries.

A new study by researchers from Children’s National Health System find that regions of the United States with the strictest gun laws also have the fewest emergency department visits for pediatric firearm-related injuries. The work is among the few studies to evaluate the association between local laws and firearm-related injury to children and youth. The results, presented at the 2017 annual meeting of the Pediatric Academic Societies, could inform policies at the state and regional levels.

“Our results suggest an association between regional gun laws and firearm-related injuries in children,” says Monika K. Goyal, M.D., M.S.C.E., director of research within Children’s Division of Emergency Medicine and senior author of the poster. “Regions with stricter gun laws had lower incidence rates of firearm-related emergency department visits by children.”

Firearm-related injuries are a leading cause of death and disability among children and adolescents in the United States. It is well established that states with more restrictive gun laws have fewer firearm-related fatalities. However, it has been unclear how these laws affect the rates of firearm-related injuries among children.

To investigate this question, Children’s National researchers gathered data from the Nationwide Emergency Department Sample (NEDS), a set of hospital-based emergency department databases created by the federal Agency for Healthcare Research and Quality to aggregate data about emergency department visits across the country. The researchers matched NEDS data from 2009 to 2013 in patients 21 and younger with state-level Brady Gun Law Scores, a measure of the strength of firearm laws, in four geographic regions: The Midwest, Northeast, South and West.

The researchers found that during this five-year study period, there were 111,839 emergency department visits for pediatric firearm-related injuries nationwide, an average of 22,368 per year. The mean age of patients was 18 years, and the vast majority was male. Just over one-third were publicly insured. About 30 percent of these recorded injuries resulted in hospital admission, and about 6 percent resulted in death.

Overall, firearm-related visits to emergency departments remained consistent over time at a rate of 65 per every 100,000 visits until 2013, when they decreased slightly to 51 per 100,000 visits. However, these rates varied significantly by geographic region. The Northeast had the lowest rate at 40 per 100,000 visits. This was followed by the Midwest, West and South at 62, 68 and 71 per 100,000 visits, respectively.

These numbers roughly matched the Brady Gun Law Scores for each region. The Northeast had the highest Brady score at 45, followed by 8, 9 and 9 for the South, West and Midwest.

These findings, the study authors say, suggest that stricter gun laws might lead to fewer fatalities as well as fewer gun-related injuries among children. Future studies about the role of regional gun culture and its impact on firearm legislation at the regional level, they say, is an important next step in advocating for changes to firearm legislation and reducing pediatric firearm-related injuries.

“Future research work should seek to elucidate the association of specific gun laws with the incidence rates of pediatric firearm-related injuries,” says Shilpa Patel, M.D., M.P.H., an assistant professor of pediatrics and emergency medicine at Children’s National and co-author of the poster. “This work also could evaluate how regional differences — such as social gun culture, gun ownership and other factors — contribute to the significant regional variation in firearm legislation.”

The American Academy of Pediatrics, an organization of 66,000 pediatricians, has repeatedly advocated for stricter gun laws, violence prevention programs, research for gun violence prevention and public health surveillance, physician counseling to patients on the health hazards of firearms and mental health access to address exposure to violence.

Cardiac Intensive Care Unit

Michael Bell to head Division of Critical Care

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Cardiac Intensive Care Unit

Michael J. Bell, M.D., will join Children’s National as Chief of the Division of Critical Care Medicine, in April 2017.

Dr. Bell is a nationally known expert in the field of pediatric neurocritical care, and established the pediatric neurocritical care program at the Children’s Hospital of UPMC in Pittsburgh.

He is a founding member of the Pediatric Neurocritical Care Research Group, an international consortia of 40 institutions dedicated to advancing clinical research for children with critical neurological illnesses. Prior to joining the University of Pittsburgh, Dr. Bell served on the faculty at Children’s National and simultaneously conducted research on the impact of inflammation on the developing brain at the National Institute of Neurological Disorders and Stroke (NINDS), within the laboratory of the Chief of the NINDS Stroke Branch.

Dr. Bell also leads the largest study to date evaluating the impact of interventions on the outcomes of infants and children with severe traumatic brain injury (TBI) and analyzing findings to improve clinical practice across the world. The Approaches and Decisions for Acute Pediatric Traumatic Brain Injury (ADAPT) Trial, funded by NINDS, has enrolled 1,000 children through 50 clinical sites across eight countries and compiled an unmatched database, which will be used to develop new guidelines for clinical care and research on TBIs. Dr. Bell is currently working on expanding the scope and continuing the trial for at least the next 5 years.

In his time at Children’s National, he played a critical role in building one of the first clinical pediatric neuro-critical care consult services in the country, which established common protocols between Children’s Divisions of Critical Care Medicine, Neurology, and Neurosurgery aimed at improving clinical care of children with brain injuries. Dr. Bell’s current research interests include: barriers to implementation of traumatic brain injury guidelines, the effect of hypothermia on various brain injuries and applications for neurological markers in a clinical setting.

The Children’s National Division of Critical Care Medicine is a national leader in the care of critically ill and injured infants and children, with clinical outcomes and safety measures among the best in the country across the pediatric, cardiac, and neuro critical care units.

Dr. Kurt Newman and HHS Secretary Price

Kurt Newman: prioritize children in health care

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Dr. Kurt Newman and HHS Secretary Price

Children’s National President and CEO Dr. Kurt Newman welcomed Secretary of Health and Human Services Tom Price to the hospital for his first official visit as a member of the Cabinet.

On February 14, Children’s National President and CEO Dr. Kurt Newman met with Secretary of Health and Human Services Tom Price at Children’s National. As part of his first official visit as a member of the Cabinet Dr. Price, who is an orthopaedic surgeon by training, toured our clinics and engaged in open dialogue with patients and families, clinicians, and members of the Children’s National leadership team.

The visit highlighted the excellence of Children’s National care providers and the essential role pediatric hospitals play in helping kids grow up stronger. It was also an opportunity to ensure that children’s health needs are top of mind for a leader who will be central to shaping policies that affect millions of America’s kids.

In their conversations, Dr. Newman emphasized the need for continued investment and dedicated health care infrastructure to support specialized care and research for children – an approach he outlined in detail this week in an op-ed in the Washington Post.

Dr. Newman intends to continue engaging directly with policy leaders and speaking up for children during this pivotal period for the nation’s health care system.

Learn more about advocacy efforts at Children’s National.