Pulmonology & Lung Surgery

emergency signs

Social risk interventions significantly reduce asthma-related ED visits

emergency signs

In a systematic review and meta-analysis published in JAMA Pediatrics, researchers at Children’s National Hospital found that interventions focused on health, environment and community were associated with the greatest reduction in asthma-related emergency department visits and hospitalizations among children.

In a systematic review and meta-analysis published in JAMA Pediatrics, researchers at Children’s National Hospital found that interventions focused on health, environment and community were associated with the greatest reduction in asthma-related emergency department visits and hospitalizations among children. The findings suggest that addressing social risks may be a crucial component of pediatric asthma care to improve health outcomes.

“There are persistent and striking disparities in asthma outcomes among children,” said Jordan Tyris, M.D., hospitalist fellow at Children’s National and lead author. “Understanding how to address these is of utmost importance.”

“Literature on the spectrum of social factors, including social needs, social risks and social determinants, has increased recently across many aspects of health care,” adds Dr. Tyris. “But much of this literature has focused on adults with chronic conditions, for example diabetes or high blood pressure.”

The study authors searched PubMed, Scopus, PsychINFO, SocINDEX and CINAHL from January 2008 to June 2021 for U.S.-based studies evaluating the associations of interventions addressing one or more social risks with asthma-related emergency department visits and hospitalizations among children. The systematic review included 38 of the original 641 identified articles (6%), and the meta-analysis included 19 articles (3%). Overall, participation in social risk–based interventions, particularly those that addressed health literacy, home environmental conditions and peer support were associated with significantly reduced risks for asthma-related emergency department visits and hospitalizations among children.

You can read the full study, “Social Risk Interventions and Health Care Utilization for Pediatric Asthma: A Systematic Review and Meta-analysis” in JAMA Pediatrics.

boy using a nebulizer

Algorithm for antibiotic use benefits patient care in cystic fibrosis

boy using a nebulizer

Despite national consensus guidelines for antibiotic treatment for pulmonary exacerbations in people with CF, prior research and systematic reviews have repeatedly demonstrated a longstanding lack of sufficient evidence for empiric antibiotic therapy recommendations, leading to a significant variation in how antibiotics are prescribed across CF care centers in the United States.

In a recent quality improvement project, researchers from Children’s National Hospital found that antimicrobial stewardship initiatives are beneficial in standardizing care and fostering positive working relationships between cystic fibrosis (CF) pulmonologists, infectious disease physicians and pharmacists.

Antimicrobial stewardship is a systematic effort to change prescribing attitudes that can provide benefit for people with CF. The objective of this effort was to decrease unwarranted use of broad-spectrum antibiotics for children and adolescents with CF. Through initiation of the empiric antibiotic algorithm, researchers found that the proportion of pulmonary exacerbations with antibiotic use consistent with the algorithm increased from 46.2% to 79.5%.

“This work will provide people with CF the expectation of a more consistent approach in their care, as well as the benefits of care from a multidisciplinary team of experts,” said Andrea Hahn, M.D., an infectious diseases specialist at Children’s National and co-author. “Implementing antimicrobial stewardship in the context of care to persons with CF provides benefit in this complex patient population.”

Despite national consensus guidelines for antibiotic treatment for pulmonary exacerbations in people with CF, prior research and systematic reviews have repeatedly demonstrated a longstanding lack of sufficient evidence for empiric antibiotic therapy recommendations, leading to a significant variation in how antibiotics are prescribed across CF care centers in the United States.

The researchers found that implementing antimicrobial stewardship when caring for people with CF provides benefit in this complex patient population.

“We would encourage other CF centers to explore their own trends in practice to determine whether a similar intervention may be both feasible and beneficial in the treatment of pulmonary exacerbations in persons with CF,” said Dr. Hahn.

computer circuit board

Integrating clinical parameters with lung imaging to predict respiratory outcomes in premature babies

computer circuit board

The team will develop an objective framework to predict the risk and assess the severity of respiratory disease in premature babies using non-invasive low-radiation X-ray imaging biomarkers and clinical parameters from the patient bedside.

Children’s National Hospital received a $1.7M award from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) to develop computational tools that integrate continuous clinical parameters with lung imaging to predict respiratory outcomes for babies born severely premature in newborn intensive care unit (NICU) settings.

The multi-disciplinary team of internationally recognized experts in quantitative imaging, machine learning and neonatal respiratory research believes they can improve clinical practice. To get there, they will develop an objective framework to predict the risk and assess the severity of respiratory disease in premature babies using non-invasive low-radiation X-ray imaging biomarkers and clinical parameters from the patient bedside.

“This computational tool will assist clinicians in making critical decisions about the course of therapy and other necessary follow-ups,” said Gustavo Nino, M.D., M.S.H.S., D’A.B.S.M., principal investigator in the Center for Genetic Medicine at Children’s National. “An objective informed decision about the severity of lung disease in prematurity will result in fewer rehospitalizations, better long-term outcomes and life-saving benefits.”

Prematurity is the largest single cause of death in children under five in the world. Lower respiratory tract infections (LRTI) are the top cause of hospitalization and mortality in premature infants. Clinical tools to predict the risk and assess the severity of LRTI in premature babies are needed to allow early interventions that can decrease the high morbidity and mortality in this patient group.

“Our new technology will provide clinicians an accurate, fast and comprehensive summary of the respiratory status of premature babies,” said Dr. Nino. “The data analysis along with the software technology will help determine if a premature baby seen in the NICU can be safely discharged or will require further monitoring and treatment.”

Predictive analytics could help in many ways. For example, there are instances where newborns in the NICU are on the right path with no risks in the future, but there are babies who will come back with severe infections.

“In the first scenario, if we can predict earlier that they’re fine, this could reduce the number of chest X-rays and extra tests, so we assess that this child can be safely sent home,” said Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National. “On the other hand, for kids that may come back to the hospital in the near future, we could predict earlier that they are not that well by looking at images and other continuous measurements such as supplemental oxygen.”

This approach, in essence, is a collection of continuous data from the NICU, which is very complex itself because it needs to be collected every day and fed into a machine learning model that digests the data to identify risk patterns for the health of the lung.

“If we find that there is still a risk, it does not necessarily mean that the child has to stay in the NICU any longer, but they might continue treatment, and we will have to define how this integrates into the clinical management of these patients,” said Linguraru. “If there is something in the data that we can put our finger on, we will know which kids require timely attention, hopefully reducing future adverse situations with potential comorbidities and financial burdens.”

insulin pump

Diabetes technology use in the cystic fibrosis community

insulin pump

Although diabetes technologies are associated with improvements in glycemic control and health-related quality of life among people with type 1 diabetes (T1D), the use and perceptions of continuous glucose monitors (CGM) and insulin pumps within the cystic fibrosis (CF) community have not been well documented.

In a recent study published in Diabetes Technology & Therapeutics, Brynn Marks, M.D., MS-HPEd, and co-authors, found that compared to T1D, rates of sustained diabetes technology use in the cystic fibrosis-related diabetes (CFRD) community are low, despite perceived benefits. The authors conclude that better insurance coverage to mitigate cost, better patient education and confirmation that these technologies improve health and patient-reported outcomes may increase uptake.

Read the full article in Diabetes Technology & Therapeutics.

smiling baby sleeping

Link between early lower respiratory tract infections and obstructive sleep apnea

smiling baby sleeping

For the first time, researchers at Children’s National Hospital have identified the association between early LRTI and the development of OSA in children.

Several birth cohorts have defined the pivotal role of early lower respiratory tract infections (LRTI) in the inception of pediatric respiratory conditions. However, the association between early LRTI and the development of obstructive sleep apnea (OSA) in children had not previously been made.

Now, for the first time, researchers at Children’s National Hospital have identified the association between early LRTI and the development of OSA in children, according to a study published in the journal SLEEP.

“These results suggest that respiratory syncytial virus LRTI may contribute to the pathophysiology of OSA in children,” said Gustavo Nino, M.D., director of sleep medicine at Children’s National.

The study also demonstrated that children with a history of severe respiratory syncytial virus (RSV) bronchiolitis during early infancy had more than double the odds of developing OSA during the first five years of life independently of other risk factors.

“The results suggest that RSV LRTI may contribute to the pathophysiology of OSA in children, raising concern for the possibility that primary prevention strategies can hinder the initial establishment of OSA following early viral LRTIs,” said Dr. Nino. “Primary prevention of OSA in children would have a dramatic effect in reducing the increasing incidence of this condition and in preventing its detrimental effects on childhood health and beyond.”

The novel findings also raise the possibility that anticipatory strategies and interventions can be developed to identify and prevent the initial establishment of OSA following viral respiratory infections during early infancy. This could provide a dramatic effect in reducing the increasing incidence of this condition and its multiple detrimental effects on childhood health and beyond.

“Our study offers a new paradigm for investigating mechanisms implicated in the early pathogenesis of OSA in the pediatric population,” said Dr. Nino.

Marishka Brown, Ph.D., director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), agreed.

“The findings from this study suggest that viral lower respiratory tract infections could predispose to the development of sleep-disordered breathing in later childhood,” Brown said. “More research to determine how these infections affect airway function could lead to a better understanding of how sleep apnea develops in pediatric patients.”

This study includes funding support from the NIH, including the NHLBI.

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

x-ray of child's chest with COVID

Chest X-rays help distinguish COVID-19 from other types of viral respiratory infections

x-ray of child's chest with COVID

COVID-19 in a 9-month infant demonstrating a GGO/consolidation pattern.

Increased infections of COVID-19 and other respiratory viruses in kids are filling up children’s hospitals, pushing them to critical occupancy nationwide. As schools open, the community spread of viral infections has become more common, and the rapid differentiation of pediatric COVID-19 from other viruses is — more than ever — relevant to pediatric clinicians.

“Pediatric cases have increased exponentially and currently represent over 15% of the total cases, and about 26% of the new infections in the U.S. Chest imaging is a powerful tool for determining their status.” said Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital.

In a new peer-reviewed study, researchers from Children’s National found novel and clinically relevant data regarding the specific lung imaging patterns of pediatric COVID-19 on chest radiographs (CXR), their relationship to clinical outcomes and the possible differences from infections caused by other respiratory viruses in children.

“While most studies have focused on clinical manifestations and lung imaging of COVID-19 in adults, this study is the first to define specific patterns of clinical disease and imaging signatures in CXR in different age groups of children infected with COVID-19,” said Gustavo Nino, M.D., director of sleep medicine at Children’s National.

Lung imaging has become critically important for the early identification and treatment of pediatric patients affected by COVID-19 and may play an important role in distinguishing COVID-19 infection from viral bronchiolitis.

“The old perception that COVID-19 only affects older patients is no longer true,” said Dr. Nino. “Pediatric intensive care units and emergency departments are overwhelmed with COVID-19 cases, and now hospitals are admitting more children with COVID-19 than ever.”

As next steps, Nino et al. will develop pediatric-centered technology for early identification, risk stratification, and outcome prediction of COVID-19 in children, similar to what the scientific community has done for adults.

RSV infected infant cells

$2.13M grant accelerates treatments for kids with Down syndrome experiencing respiratory viruses

RSV infected infant cells

Children’s National Hospital received a combined $2.13 million award from the National Institutes of Health’s (NIH) National Heart, Lung and Blood Institute to better understand the mechanisms of severe viral respiratory infections in patients with Down syndrome and to develop new diagnostic tools and innovative precision medicine approaches for this vulnerable population.

“We have a unique opportunity to discover novel targets that can treat severe viral respiratory infections, including SARS-CoV-2,” said Gustavo Nino, M.D., M.S.H.S., D’A.B.S.M., principal investigator in the Center for Genetic Medicine at Children’s National. “Part of the award will help us accelerate the development of these novel approaches to prevent severe respiratory infections caused by SARS-CoV-2 and other viruses like respiratory syncytial virus infection (RSV) in children and adults with Down syndrome.”

Lower respiratory tract infections are a leading cause of hospitalization and death in children with Down syndrome. Those children have a nine times higher risk for hospitalization and mortality due to respiratory viruses that cause lower respiratory tract infections.

Chromosome 21, which is an extra chromosome copy found in patients with Down syndrome, encodes four of the six known interferon receptors, leading to hyperactivation of interferon response in Down syndrome. With the central role of interferons focused on antiviral defense, it remains puzzling how interferon hyperactivation contributes to severe viral lower respiratory tract infections in children with Down syndrome. This is an area that the researchers will explore to better manage and treat viral lower respiratory tract infections in these patients, with the support of NIH’s INCLUDE initiative. INCLUDE provides institutions with grants to help clinical research and therapeutics to understand and diminish risk factors that influence the overall health, longevity, and quality of life for people with Down syndrome related to respiratory viruses.

“While many of the other studies focus on intellectual and other disabilities, we are exploring a novel viral respiratory infectious disease mechanism and are doing so by working directly with patients and patient-derived samples,” said Jyoti Jaiswal, M.Sc., Ph.D., senior investigator in the Center for Genetic Medicine Research at Children’s National.

Children with Down syndrome have historically been excluded in research related to airway antiviral immunity, which is a focus of this human-based transformative study to improve the health and survival of patients with Down syndrome. There is a critical need for studies that define targetable molecular and cellular mechanisms to address dysregulated antiviral responses in this patient population.

“The clinical expertise at Children’s National in studying Down syndrome and the work of our team in caring for these patients with respiratory and sleep disorders positions us well to pursue this work,” said Jaiswal. “This is further supplemented by our initial studies that have identified a novel mechanism of impaired airway antiviral responses in these patients.”

Congresswoman Eleanor Holmes Norton (D-DC) also celebrated Children’s National and its NIH research funding benefitting people with Down syndrome.

“I am pleased to congratulate Dr. Nino and staff on being the recipients of the National Heart, Lung, & Blood Institute grant. You were chosen from a competitive group of applicants and should be proud of this notable achievement,” said Norton in a letter. “By receiving this grant, you have demonstrated outstanding promise in your field. It is my hope that this grant will enable you to better the local and global community.”

Bear Institute PACK logo

Winners of the first annual Bear Institute PACK Event

Bear Institute PACK logo

On August 26, 2021, the Bear Institute, along with Children’s National Hospital and Cerner Corporation, hosted the first annual Bear Institute PACK (Pediatric Accelerator Challenge for Kids). Bear Institute PACK is a start-up competition aimed to address the gap in digital health innovation funding dedicated to children.

“Children are a unique population that requires different health solutions than those designed for adults, which address their unique needs,” says Dr. Lu de Souza, Vice President and Chief Medical Officer, Cerner Corporation. “With Bear Institute PACK, we hope to increase focus and delivery of digital health innovations for kids. Bear Institute PACK brings together the pediatric health care community, including pediatric health care providers and hospital administrators from across the country to identify top start-up digital applications that best serve children.”

This year’s start-up participants competed across four innovation tracks, including rare disease, telemedicine, remote patient monitoring and patient education. Student teams competed in a separate student track. Bear Institute PACK consists of three rounds of judging: an initial review of applications from the Bear Institute PACK team, judging from participating pediatric healthcare providers and administrators and review from an expert panel of judges during finalist start-ups’ live pitches.

The start-ups competed for a rich prize pool, including cash prizes totaling over $100,000, on-site pilots and software development support. Winners were selected in each of the event’s four innovation tracks, as well as an additional two student team winners. This year winners are:

  • In the rare disease track, first place winner, Bloom Standard, Inc., with its solution Automated Ultrasound Wrap that screen infants and children for serious lung and cardiac conditions, and second place winner, Mira Medical LLC, with its solution Bear Growth: A Three-Dimensional Pediatric Growth Modeling App.
  • In the telehealth track, Keriton, Inc., with its solution Keriton Kare, a healthcare SaaS platform built to improve outcomes for neonatal and pediatric patients.
  • In the remote patient monitoring track, Sonavi Labs, with its solution Feelix, a platform that features proprietary hardware embedded with clinically validated diagnostic software capable of detecting respiratory diseases.
  • In the patient education track, Smileyscope, with its comprehensive virtual reality (VR) platform to help support patients with procedural pain management, drug-free anxiety care, education, and guided relaxation.
  • Student team first place winner, CASP Technologies, with its solution Operation Serenity, which allows pediatric patients to prepare for and understand their simulated surgery to reduce anxiety and second place winner, Ankle Rehab, with its solution Foot Joystick for Children with Cerebral Palsy meant to improve mobility.

More information on this year’s winners can be found on the Bear Institute PACK website.

“This year’s Bear Institute PACK had a lot of start-ups and student team participants with very impressive innovation solutions for kids. Selecting a single winner in each innovation track was a tough decision, and it was encouraging to see all the work being done to bring these solutions to market,” says Matt MacVey, Vice President and Chief Information Officer, Children’s National Hospital. “Thank you to everyone who participated and helped make the inaugural Bear Institute PACK a success! We hope to make next year even bigger as we continue to strive to close the gap in funding for children’s digital health innovation.”

More information on next year’s event will be forthcoming on the Bear Institute PACK website.

pill bottles and pills

Impact of anaerobic antibacterial spectrum on cystic fibrosis

Researchers from Children’s National Hospital found that broad spectrum antianaerobic therapy had greater and longer lasting effects on the lung microbiome of persons with cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the chloride ion channel encoding CF transmembrane conductance regulator gene, leading to multiple morbidities and early mortality. In a new clinical study, researchers from Children’s National Hospital found that broad spectrum antianaerobic therapy had greater and longer lasting effects on the lung microbiome of persons with CF.

They found this difference when comparing the microbiology and clinical outcomes in children with CF who were treated with “broad” or “narrow” antianaerobic antibiotics for exacerbations of their disease. While there are many factors that determine whether “narrow” or “broad” spectrum antibiotics are used, the data showed that the recovery of pulmonary function was similar between those groups.

“The findings prove that most providers are following best practices when treating patients with cystic fibrosis using the narrowest spectrum of antibiotics possible, and reserving broad spectrum agents for more advanced disease when culture data shows more resistant bacteria,” says  Michael Bozzella, the study’s lead author.

The study, published in the Pediatric Infectious Disease Journal, analyzed how the spectrum of antibiotics prescribed to patients with cystic fibrosis impacts the population of bacteria in their lungs how it ties back to lung function.

“Research like this improves antibiotic and antimicrobial stewardship,” said Bozzella. “When speaking with families and patients with cystic fibrosis, providers can be more aware of the relationship between lung microbiome, disease state, and antibiotics and create more holistic treatment plans.”

Dr. Bozzella did this research as a fellow at Children’s National and he’s now an Infectious Disease Attending Physician at Children’s Hospital Colorado. Additional authors from Children’s National include: Andrea Hahn, M.D., M.S., Hollis Chaney, M.D.Iman Sami Zakhari, M.D.Anastassios Koumbourlis, M.D., M.P.H. and Robert Freishtat, M.D., M.P.H.

coronavirus

Children’s National Hospital and NIAID launch large study on long-term impacts of COVID-19 and MIS-C on kids

coronavirus

Up to 2,000 children and young adults will be enrolled in a study from Children’s National Hospital in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) that will examine the long-term effects of COVID-19 and multisystem inflammatory syndrome in children (MIS-C) after these patients have recovered from a COVID-19 infection.

This $40 million multi-year study will provide important information about quality of life and social impact, in addition to a better understanding of the long-term physical impact of the virus, including effects on the heart and lung. The researchers hope to detail the role of genetics and the immune response to COVID-19, so-called “long COVID” and MIS-C, including the duration of immune responses from SARS-CoV-2, the virus that causes COVID-19. It is fully funded by a subcontract with the NIH-funded Frederick National Laboratory for Cancer Research operated by Leidos Biomedical Research, Inc.

“We don’t know the unique long-term impact of COVID-19 or MIS-C on children so this study will provide us with a critical missing piece of the puzzle,” says Roberta DeBiasi, M.D., M.S., chief of the Division of Pediatric Infectious Diseases at Children’s National and lead researcher for this study. “I am hopeful that the insights from this enormous effort will help us improve treatment of both COVID-19 and MIS-C in the pediatric population both nationally and around the world.”

Over the past year, more than 3.6 million children have tested positive for SARS-CoV-2 and over 2,800 cases of MIS-C have been reported throughout the U.S. While the vast majority of children with primary SARS-CoV-2 infection may have mild or no symptoms, some develop severe illness and may require hospitalization, including life support measures. In rare cases, some children who have previously been infected or exposed to someone with SARS-CoV-2 have developed MIS-C, a serious condition that may be associated with the virus. MIS-C symptoms can include fever, abdominal pain, bloodshot eyes, trouble breathing, rash, vomiting, diarrhea and neck pain, and can progress to shock with low blood pressure and insufficient cardiac function. Long COVID is a wide range of symptoms that can last or appear weeks or even months after being infected with the virus that causes COVID-19.

The study is designed to enroll at least 1,000 children and young adults under 21 years of age who have a confirmed history of symptomatic or asymptomatic SARS-CoV-2 infection or MIS-C. Participants who enroll within 12 weeks of an acute infection will attend study visits every three months for the first six months and then every six months for three years. Participants who enroll more than 12 weeks after acute infection will attend study visits every six months for three years. The study will also enroll up to 1,000 household contacts to serve as a control group, and up to 2,000 parents or guardians (one parent per participant) will complete targeted questionnaires.

“The large number of patients who will be enrolled in this study should provide us with a truly comprehensive understanding of how the virus may continue to impact some patients long after the infection has subsided,” says Dr. DeBiasi.

The study primarily aims to determine incidence and prevalence of, and risk factors for, certain long-term medical conditions among children who have MIS-C or a previous SARS-CoV-2 infection. The study will also evaluate the health-related quality of life and social impacts for participants and establish a biorepository that can be used to study the roles of host genetics, immune response and other possible factors influencing long-term outcomes.

Children’s National was one of the first U.S. institutions to report that children can become very ill from SARS-CoV-2 infection, despite early reports that children were not seriously impacted. In studies published in the Journal of Pediatrics in May of 2020 and June of 2021, Children’s National researchers found that about 25% of symptomatic COVID patients who sought care at our institution required hospitalization. Of those hospitalized, about 25% required life support measures, and the remaining 75% required standard hospitalization. Of patients with MIS-C, 52% were critically ill.

Study sites include Children’s National Hospital inpatient and outpatient clinics in the Washington, D.C. area, and the NIH Clinical Center in Bethesda, Maryland.

Those interested in participating should submit this form. You will then be contacted by a study team member to review the study details and determine whether you are eligible to participate.

You can find more information about the study here.

little boy at doctor

Demographic, clinical and biomarker features of MIS-C

little boy at doctor

In a new observational study, researchers provide insight into key features distinguishing MIS-C patients to provide a more realistic picture of the burden of disease in the pediatric population and aid with the early detection of disease and treatment for optimal outcomes.

Multisystem Inflammatory Syndrome in Children (MIS-C) significantly affected more Black and Latino children than white children, with Black children at the highest risk, according to a new observational study of 124 pediatric patients treated at Children’s National Hospital in Washington, D.C. Researchers also found cardiac complications, including systolic myocardial dysfunction and valvular regurgitation, were more common in MIS-C patients who were critically ill. Of the 124 patients, 63 were ultimately diagnosed with MIS-C and were compared with 61 patients deemed controls who presented with similar symptoms but ultimately had an alternative diagnosis.

In the study, published in The Journal of Pediatrics, researchers provide insight into key features distinguishing MIS-C patients to provide a more realistic picture of the burden of disease in the pediatric population and aid with the early detection of disease and treatment for optimal outcomes. The COVID-linked syndrome has affected nearly 4,000 children in the United States in the past year. Early reports showed severe illness, substantial variation in treatment and mortality associated with MIS-C. However, this study demonstrated that with early recognition and standardized treatment, short-term mortality can be nearly eliminated.

“Data like this will be critical for the development of clinical trials around the long-term implications of MIS-C,” says Dr. Roberta DeBiasi, M.D., lead author and chief of the Division of Pediatric Infectious Diseases at Children’s National. “Our study sheds light on the demographic, clinical and biomarker features of this disease, as well as viral load and viral sequencing.”

Of the 63 children with MIS-C, 52% were critically ill, and additional subtypes of MIS-C were identified including those with and without still detectable virus, those with and without features meeting criteria for Kawasaki Disease, and those with and without detectable cardiac abnormalities. While median age (7.25 years) and sex were similar between the MIS-C cohort and control group, Black (46%) and Latino (35%) children were overrepresented in the MIS-C group, especially those who required critical care. Heart complications were also more frequent in children who became critically ill with MIS-C (55% vs. 28%). Findings also showed MIS-C patients demonstrated a distinct cytokine signature, with significantly higher levels of certain cytokines than those of controls. This may help in the understanding of what drives the disease and which potential treatments may be most effective.

In reviewing viral load and antibody biomarkers, researchers found MIS-C cases with detectable virus had a lower viral load than in primary SARS-CoV-2 infection cases, but similar to MIS-C controls who had alternative diagnoses, but who also had detectable virus. A larger proportion of patients with MIS-C had detectable SARS-CoV-2 antibodies than controls. This is consistent with current thinking that MIS-C occurs a few weeks after a primary COVID-19 infection as part of an overzealous immune response.

Viral sequencing was also performed in the MIS-C cohort and compared to cases of primary COVID-19 infection in the Children’s National geographic population. 88% of the samples analyzed fell into the GH clade consistent with the high frequency of the GH clade circulating earlier in the pandemic in the U.S. and Canada, and first observed in France.

“The fact that there were no notable sequencing differences between our MIS-C and primary COVID cohorts suggests that variations in host genetics and/or immune response are more likely primary determinants of how MIS-C presents itself, rather than virus-specific factors,” says Dr. DeBiasi. “As we’ve seen new variants continue to emerge, it will be important to study their effect on the frequency and severity of MIS-C.”

Researchers are still looking for consensus on the most efficacious treatments for MIS-C. In a recent editorial in the New England Journal of Medicine, Dr. DeBiasi calls for well-characterized large prospective cohort studies at single centers, and systematic and long-term follow-up for cardiac and non-cardiac outcomes in children with MIS-C. Data from these studies will be a crucial determinant of the best set of treatment guidelines for immunotherapies to treat MIS-C.

US News badges

For fifth year in a row, Children’s National Hospital nationally ranked a top 10 children’s hospital

US News badges

Children’s National Hospital in Washington, D.C., was ranked in the top 10 nationally in the U.S. News & World Report 2021-22 Best Children’s Hospitals annual rankings. This marks the fifth straight year Children’s National has made the Honor Roll list, which ranks the top 10 children’s hospitals nationwide. In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fifth year in a row.

For the eleventh straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“It is always spectacular to be named one of the nation’s best children’s hospitals, but this year more than ever,” says Kurt Newman, M.D., president and CEO of Children’s National. “Every member of our organization helped us achieve this level of excellence, and they did it while sacrificing so much in order to help our country respond to and recover from the COVID-19 pandemic.”

“When choosing a hospital for a sick child, many parents want specialized expertise, convenience and caring medical professionals,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings have always highlighted hospitals that excel in specialized care. As the pandemic continues to affect travel, finding high-quality care close to home has never been more important.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

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

Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:

The other three specialties ranked among the top 50 were cardiology and heart surgerygastroenterology and gastro-intestinal surgery, and urology.

mother helping child with inhaler

Beta-lactam and microbial diversity in cystic fibrosis

mother helping child with inhaler

The study, published in the Journal of Investigative Medicine, examined the hypotheses that beta-lactam antibiotic PK and PD is associated with changes in richness and alpha diversity following treatment of a pulmonary exacerbations and determined associations between antibiotic PK, PD, antibiotic resistance and lung function.

Cystic fibrosis (CF) is a chronic lung disease that affects more than 30,000 people in the United States and 70,000 people worldwide. While this chronic disease is characterized by acute pulmonary exacerbations that are frequently treated with antibiotics, the impact of antibiotics on airway microbial diversity remains a critical knowledge gap.

A new study led by researchers at Children’s National Hospital found that beta-lactam antibiotic pharmacokinetic (PK) and pharmacodynamic (PD) target attainment during treatment is associated with suppressed recovery of microbial diversity, following a pulmonary exacerbation in children and adolescents with CF.

“By laying the groundwork for understanding how antibiotic PK may influence microbial diversity following pulmonary exacerbation, we hope to identify improved ways to guide antibiotic therapy in persons with CF,” says Andrea Hahn, M.D., M.S., an infectious diseases specialist at Children’s National and lead author of the study.

The study, published in the Journal of Investigative Medicine, examined the hypotheses that beta-lactam antibiotic PK and PD is associated with changes in richness and alpha diversity following treatment of a pulmonary exacerbations and determined associations between antibiotic PK, PD, antibiotic resistance and lung function.

“Beta-lactam antibiotics are frequently used to treat pulmonary exacerbations in persons with CF, yet are not routinely optimized,” says Dr. Hahn. “This study demonstrates the importance of beta-lactam PK’s on changes within the airway microbiome and provides context for care providers regarding the potential long-term impacts of antibiotic use in persons with CF, to ensure that we are optimizing therapy with each pulmonary exacerbation.”

Additional authors from Children’s National include: Aszia Burrell, Hollis Chaney, M.D.Iman Sami Zakhari, M.D.Anastassios Koumbourlis, M.D., M.P.H. and Robert Freishtat, M.D., M.P.H.

Children’s National Pulmonary Medicine Rockville

Spotlight on Samuel Rosenberg, M.D.

Children’s National Pulmonary Medicine Rockville

Dr. Rosenberg will be seeing patients at Children’s National Pulmonary Medicine Rockville (above) and Children’s National Frederick.

Samuel Rosenberg, M.D., a Maryland native, has been practicing medicine in the Washington, D.C., area since he completed his post-graduate medical training in 1991. For the last 27 years, he has served Montgomery County, Frederick County and the surrounding communities through his private practice in pediatric pulmonology. Now, he has joined the Children’s National Hospital team as a member of our pulmonology faculty.

Growing up, Dr. Rosenberg always knew that his life goal was to help people. Given that he also had a natural affinity for science, medicine seemed to be a perfect fit. After completing a combined internal medicine and pediatrics residency program, Dr. Rosenberg found his calling in pediatrics. “I quickly realized that pediatrics was far more rewarding from a personal perspective,” he recalls. “I also became fascinated with diseases of the pulmonary system during my residency and chose to pursue pediatric pulmonology as a career.”

After completing his medical training, Dr. Rosenberg became a staff pediatric pulmonologist at Inova Children’s Hospital for three years before starting his own solo private practice. After spending 27 years in that practice, he has chosen to join the team at Children’s National. “I wanted to be associated with and have access to a diverse and top-notch health care team for my patients and my practice,” he explains. “I would also like to participate in teaching students and trainees, something that has always been of interest to me.”

In his many years as a pediatric pulmonologist, Dr. Rosenberg has found that serving patients and families remains the most rewarding aspect of his work. “My biggest accomplishment is helping children, and at the same time, enjoying my work. I have many patients who have been in my practice since infancy. They have placed their trust in me over the years, and I appreciate that trust so much,” he explains. “I treasure my relationships with my patients and families. Improving their quality of life has always been my primary focus.”

In his new role with Children’s National, Dr. Rosenberg will continue to provide quality care to his patients and families. “I am committed to continuing to practice medicine at the highest level, while at the same time preserving a comfortable child and family-friendly environment,” he says. He will be seeing patients at Children’s National Pulmonary Medicine Rockville and Children’s National Frederick.

girl with asthma inhaler

Children’s National becomes part of CAUSE Network

girl with asthma inhaler

Seven clinical sites in six different cities will join forces to perform mechanistic and translational studies examining the basic immunology of pediatric asthma among urban, under-resourced and largely minority children and adolescents.

The National Institute of Allergy and Infectious Diseases (NIAID) allocated $10 million in funding to establish the Childhood Asthma in the Urban Setting (CAUSE) network. The NIAID plans to increase this number by $70 million over seven years to support the network. Children’s National Hospital will be part of the new research network, which is a 7-year consortium comprising of seven clinical sites in six different cities that will join forces to perform mechanistic and translational studies examining the basic immunology of pediatric asthma among urban, under-resourced and largely minority children and adolescents.

Children’s National is the home of Improving Pediatric Asthma Care in the District of Columbia (IMPACT DC). The program focuses on research, care and advocacy to decrease asthma morbidity experienced by at-risk youth in the region while serving as a model program for the nation. NIAID gave an initial $3 million to IMPACT DC to conduct its own pilot study of anti-IgE therapy to prevent asthma exacerbations. Additional support for this and other studies will come from subcontracts from the CAUSE Coordinating Center at the University of Wisconsin in Madison.

“This new award allows IMPACT DC to remain part of one of the nation’s most prestigious pediatric asthma research consortia,” said Stephen Teach, M.D, M.P.H., chair for the Department of Pediatrics at George Washington University School of Medicine and Health Sciences. “It will allow us to both pursue an independent research agenda while collaborating with similar academic centers nationwide.”

Pediatric asthma is the most common chronic disease in children, and it is estimated that about 6.1 million children under 18 years suffer from this condition. It disproportionately affects urban, minority and under-resourced children and adolescents.

“It is essential to develop an understanding of the basic immunology of the disease and therapeutic options to ameliorating these disparities,” said Dr. Teach.

CAUSE researchers will explore the mechanisms of immune tolerance to allergens, the role of early environmental exposures in the pathogenesis of asthma, the pathogenesis and mechanisms of non-atopic asthma, the role of the respiratory epithelium in asthma and more.

The CAUSE network comprises of seven clinical research centers, including Children’s National led by principal investigator, Dr. Teach, and the following research centers:

  • Boston Children’s Hospital. Principal investigators: Wanda Phipatanakul, M.D., and Talal Chatila, M.D.
  • Cincinnati Children’s Hospital Medical Center. Principal investigator: Gurjit Khurana Hershey, M.D., Ph.D.
  • Columbia University Health Sciences, New York. Principal investigator: Meyer Kattan, M.D.
  • Icahn School of Medicine at Mount Sinai, New York. Principal investigators: Paula Busse, M.D., Supinda Bunyavanich, M.D., and Juan Wisnivesky, M.D.
  • Lurie Children’s Hospital of Chicago. Principal investigators: Rajesh Kumar, M.D., and Jacqueline Pongracic, M.D.
  • University of Colorado Denver. Principal investigator: Andrew Liu, M.D.
Francis Collins

Francis S. Collins, M.D., Ph.D. from NIH: The future of genomic medicine and research funding opportunities

Kurt Newman and Francis Collins

Genomic medicine, diversity, equity and inclusion (DEI), a world post-COVID-19 and pediatric research funding were among the topics discussed during the “Special Fireside Chat” keynote lecture at the 2021 Children’s National Hospital Research, Education and Innovation Week.

Francis S. Collins, M.D., Ph.D., director at the National Institutes of Health (NIH), is well known for his landmark discoveries of disease genes and his leadership of the international Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book.

The President and CEO of Children’s National, Kurt Newman, M.D., joined Dr. Collins during the “Special Fireside Chat” keynote lecture. Dr. Newman posed several health care-related questions to Dr. Collins over the course of 30 minutes. Dr. Collins’s responses shed light on what it takes to advance various research fields focused on improving child health and develop frameworks that advocate for DEI in order to foster a more just society.

Q: You have been involved with genomic medicine since its inception. You discovered the gene causing cystic fibrosis and led the Human Genome project. What do you see as the future of genomic medicine, especially as it relates to improving child health?

A: Thank you for the question, Kurt. First, I wanted to say congratulations on your 150th anniversary. Children’s National Hospital has been such a critical component for pediatric research and care in the Washington, D.C., area, and at the national and international levels. We at the NIH consider it a great privilege to be your partner in many of the things that we can and are doing together.

Genomic medicine has certainly come a long way. The word genomics was invented in 1980, so we have not been at this for that long. Yet, the success of the Human Genome Project and the access to cost-effective tools for rapid DNA sequencing have made many things possible. It took a lot of effort, time and money to discover the gene that causes cystic fibrosis. Kurt, if you look at what we did, while it was rewarding, it was a challenging problem that occupied the hearts of the scientific community in 1980. Now, a graduate student at Children’s National that has access to DNA samples, a thermal cycler, a DNA sequencer and the internet could do in about a week what it took us a decade and with 50 people.

We have been able to rocket forward as far as identifying the genetic causes of 6,500 diseases, where we know precisely the molecular glitch responsible for those conditions. While most of those are rare diseases, it leads to the opportunity for immediate diagnosis, which used to be a long and troubled journey.

DNA sequencing has increasingly become an essential tool in newborns, especially when trying to sort out puzzling diagnosis for specific syndromes or phenotypes that are not immediately clear. Additionally, DNA sequencing significantly impacted clinical care in cancer because it made it possible to look at the mutations driving the malignancy and its genetic information that can lead to interventions. This approach is going forward in the next few years in ways that we can see now. Although I am a little reluctant to make predictions because I have to be careful about that, it may be possible to obtain complete genome sequences that can be yours for life and place them into the medical record to make predictions about future risks and choices about appropriate drugs. This path costs less than any imaging tests.

Q: The racial justice movement that was brought back to the forefront this past year has, once again, reaffirmed that this country has so much more work to do in order to end systemic racism. You have been at the forefront of promoting diversity, equity and inclusion in research and at the NIH. What do you and the NIH plan to do further DEI efforts in research and in general so that we can be a more just and equitable society?

A: I appreciate you raising this, Kurt. Diversity, equity and inclusion (DEI) is an issue where everyone should be spending a lot of time, energy and passion. You are right. 2020 will be remembered for COVID-19. I also think it will be remembered for the things that occurred around the killing of George Floyd, and the recognition of the very foundation that is still infected by this terribly difficult circumstance of structural racism. I convened a group of about 75 deep thinkers about these issues, many of them are people of color from across the NIH’s different areas of activities. I asked the group to come forward with a bold set of proposals. This effort is how the program UNITE came together to work hard on this, which is now making recommendations that I intend to follow. We are determined to close that gap and pursue additional programs that will allow us to be more successful in recruiting and retaining minority groups, for example. We need to do something with our health disparity and research portfolio as well to ensure that we are not just looking around the edges of the causes for racial inequities. We are digging deeper into what the structural racism underpinnings are and what we can do about it. I am particularly interested in supporting research projects that test intervention and not just catalog the factors involved. We have been, at times, accused and maybe rightly so of being more academic about this, and, less kindly, we have been accused of admiring the problem of health disparities as opposed to acting on it. We are ready to act.

Q: COVID has affected us all in so many ways. Could you tell us what this past year has been like for you? Also, how is the NIH preparing for a soon-to-be post-COVID pandemic?

A: This is the time to contemplate the lessons learned as everyone knows that the last worst pandemic happened over a century ago. One thing that maybe will vex us going forward, which we already started to invest in a big way, is this whole long COVID syndrome, also referred to post-acute sequelae, to understand precisely the consequences and mechanisms like Multisystem Inflammatory Syndrome in Children (MIS-C). Before moving to the next pandemic, we must think about how we will help understand those who suffer from long COVID syndrome. As far as the broader lessons learn, Kurt, we must expect that there will be other pandemics because humans are interacting more with animals, so zoonosis is likely to emerge. We need to have a clear sense of preparation for the next one. For instance, we are working on this right now, but we need to have a stronger effort to develop small molecules of anti-viral drugs aimed at the major viral classes, so we do not have to start from scratch. We also need clinical trial networks warm all the time, ready to go and to learn how valuable public partnerships can be to get things done in a hurry.

Editor’s Note: The responses in this Q+A have been modified to fit the word count.

Andrea Hahn

Pediatric Research names Andrea Hahn, M.D., M.S., early career investigator

Andrea Hahn

“I am honored to be recognized by Pediatric Research and the Society of Pediatric Research (SPR) at large,” said Dr. Hahn. “SPR is an amazing organization filled with excellent scientists, and to be highlighted by them for my work is truly affirming.”

For her work on the impact of bacterial functional and metabolic activity on acute episodes of cystic fibrosis, the journal Pediatric Research recognized Andrea Hahn, M.D., M.S., as Pediatric Research’s Early Career Investigator.

Cystic fibrosis is an autosomal recessive genetic disease, affecting more than 70,000 people worldwide. The condition’s morbidity and mortality are recurrent and result in a progressive decline of lung function.

“I am honored to be recognized by Pediatric Research and the Society of Pediatric Research (SPR) at large,” said Dr. Hahn. “SPR is an amazing organization filled with excellent scientists, and to be highlighted by them for my work is truly affirming.”

The exact mechanisms of the bacteria that chronically infect the airway triggering acute cystic fibrosis episodes, also known as pulmonary exacerbations, remain unclear. Dr. Hahn’s research is one of the few to explore this gap and found an association with long-chain fatty acid production in cystic fibrosis inflammation.

“As a physician-scientist, there are many competing priorities between developing and executing good science — including writing manuscripts and grants — and providing excellent patient care both directly and through hospital-wide quality improvement initiatives,” said Dr. Hahn. “It is often easier to have successes and feel both effective and appreciated on the clinical side. This recognition of my scientific contributions to the medical community is motivating me to continue pushing forward despite the setbacks that often come up on the research side.”

The exposure to many programs and institutions gave Dr. Hahn the foundation to create a research program at Children’s National that helps decipher the complexities of antibiotic treatment and how it changes the airway microbiome of people with cystic fibrosis. The program also explores the impacts of antibiotic resistance and beta-lactam pharmacokinetics/pharmacodynamics (PK/PD) — the oldest class of antibiotics used to treat infections.

Dr. Hahn believes that the people and environment at Children’s National Hospital allowed her to grow and thrive as a physician-scientist.

“I was initially funded through an internal K12 mechanism, which was followed up by Foundation support, which was only possible because of the strong mentorship teams I have been able to build here at Children’s National,” said Dr. Hahn. “My division chief has also been very supportive, providing me with both protected time as well as additional resources to build my research lab.”

She is particularly appreciative of Robert Freishtat, M.D., M.P.H, senior investigator at the Center for Genetic Medicine Research, and Mary Callaghan Rose (1943-2016).

“Robert Freishtat has been a great advocate for me, and I am indebted to him for my success thus far in my career,” said Dr. Hahn. “Likewise, I want to specifically recognize Mary Rose. She was a great scientist at Children’s National until her death in 2016. She gave me the initial opportunity and support to begin a career studying cystic fibrosis, and she is missed dearly.”

You can learn more about Dr. Hahn’s research in this Pediatric Research article.

girl with cystic fibrosis getting breathing treatment

The role of long-chain fatty acids in cystic fibrosis inflammation

girl with cystic fibrosis getting breathing treatment

A recent study sheds light on the microbiologic triggers for lung inflammation and pulmonary exacerbations in cystic fibrosis.

Cystic fibrosis is an autosomal recessive disease that affects more than 70,000 people worldwide and results in a progressive decline of lung function. Patients with cystic fibrosis experience intermittent episodes of acute worsening of symptoms, commonly referred to as pulmonary exacerbations. While Staphylococcus aureus and Pseudomonas aeruginosa are thought to contribute to both lung inflammation and pulmonary exacerbations, the microbiologic trigger for these events remains unknown. Andrea Hahn, M.D., M.S., and her colleagues at Children’s National Hospital recently shed light on this matter by studying the changes in bacterial metabolic pathways associated with clinical status and intravenous (IV) antibiotic exposure in cystic fibrosis patients.

The researchers found increased levels of long-chain fatty acids (LCFAs) after IV antibiotic treatment in patients with cystic fibrosis. LCFAs have previously been associated with increased lung inflammation in asthma, but this is the first report of LCFAs in the airway of people with cystic fibrosis. This research indicates that bacterial production of LCFAs may be a contributor to inflammation in people with cystic fibrosis and suggests that future studies should evaluate LCFAs as predictors of pulmonary exacerbations.

Additional authors from Children’s National include: Hollis Chaney, M.D., Iman Sami Zakhari, M.D., Anastassios Koumbourlis, M.D., M.P.H. and Robert Freishtat, M.D., M.P.H.

Read the full study in Pediatric Research.

illustration of lungs with coronavirus inside

Pediatric asthma exacerbations during the COVID-19 pandemic

illustration of lungs with coronavirus inside

The authors found that in 2020, the District of Columbia did not experience the typical “September asthma epidemic” of exacerbations seen in past years.

In the United States, pediatric asthma exacerbations typically peak in the fall due to seasonal factors such as increased spread of common respiratory viruses, increased exposure to indoor aeroallergens, changing outdoor aeroallergen exposures and colder weather. In early 2020, measures enacted to reduce spread of the coronavirus (COVID-19) — such as social distancing, quarantines and school closures — also reduced pediatric respiratory illnesses and asthma morbidity. Children’s National Hospital immunologist and allergist William J. Sheehan, M.D., and colleagues sought to determine if these measures also affected the 2020 fall seasonal asthma exacerbation peak in Washington, D.C.

The authors found that in 2020, the District of Columbia did not experience the typical “September asthma epidemic” of exacerbations seen in past years. Emergency department visits, hospitalizations and intensive care unit admissions for asthma during the 2020 fall season were significantly reduced compared to previous years.

The authors conclude that, “this is likely due to social distancing, quarantines and school closures enacted during the pandemic. This is a small silver lining in a very difficult year. As 2021 brings optimism for gradual improvements of the pandemic, careful monitoring is necessary to recognize and prepare for childhood asthma morbidity to return to pre-pandemic levels.”

Additional study authors include: Shilpa J. Patel, M.D., M.P.H., Rachel H.F. Margolis, Ph.D., Eduardo R. Fox, M.D., Deborah Q. Shelef, M.P.H., Nikita Kachroo, B.S., Dinesh Pillai, M.D. and Stephen J. Teach, M.D., M.P.H.

Read the full study in the Journal of Allergy and Clinical Immunology: In Practice.

Asthma-Related Healthcare Utilization by Month

Asthma-Related Healthcare Utilization by Month (2016-2020). Asthma-related emergency department (ED) visits, hospitalizations and pediatric intensive care unit (PICU) admissions over time by month between 2016 and 2020. The p-values are for comparisons of mean monthly numbers for fall seasons of 2016-2019 to fall season of 2020. Image courtesy of the Journal of Allergy and Clinical Immunology: In Practice.

girl with down syndrome sleeping

Characteristics of central breathing abnormalities in children with trisomy 21

girl with down syndrome sleeping

Trisomy 21 (TS21), also known as Down syndrome, is the most common genetic syndrome in the United States. Many children with TS21 have a higher prevalence of sleep-related breathing disorders including central sleep apnea. While the mechanisms of central sleep apnea in TS21 are not completely understood, children with Down syndrome have multiple factors that make them more susceptible to developing central breathing abnormalities, including nervous system impairment, hypothyroidism and hypotonia.

In a recent multi-institutional study published in the journal Pediatric Pulmonology, Gustavo Nino, M.D., MSHS, D’ABSM, director of sleep medicine at Children’s National Hospital, and colleagues investigated the clinical features of central breathing abnormalities in TS21 across different pediatric age groups. The researchers also conducted analyses to look at the effects of biological sex and concomitant obstructive sleep apnea in children with central breathing abnormalities.

The authors conclude that “central breathing abnormalities are common in TS21 among young children (≤2 years of age) and in females older than 2 years of age,” and that “central apnea is often associated with concomitant obstructive sleep apnea and/or hypoxemia in children with TS21.”

Read the full study in Pediatric Pulmonology.