Pulmonology & Lung Surgery

asthma inhaler

New study links T cells and airway muscle in obese children with asthma

asthma inhaler

The study found that T cells from obese children with asthma adhere more to the airway muscle than T cells from lean children with asthma.

Obesity-related asthma is a distinct type of asthma that is increasing among children due to an increase in obesity. It is associated with high disease burden that is not responsive to currently available asthma therapies. Researchers from Children’s National are leading the way with the first study of its kind to show a link between T cells and airway muscle. This unique work represents an important step forward in understanding pediatric obesity-related asthma and has the potential to inform the development of new treatments.

What’s been the hold-up in the field?

Researchers do not understand the mechanisms that underlie obesity-related asthma. This lack of knowledge directly affects the ability to find medications that are effective against this disease.

How does this work move the field forward?

The study found that T cells from obese children with asthma adhere more to the airway muscle than T cells from lean children with asthma. This adhesion of T cells to airway muscle causes the muscle to be more contractile. This is the first study to link immune cells in obese children with asthma with airway-specific changes.

How will this work benefit patients?

The study has identified a mechanism where immune cells react with airway muscle. As part of this, few proteins will be studied further to see if they can be targets for medications specifically for obesity-related asthma.

How is Children’s National leading in this space?

Children’s National is leading in this space by initiating a first of its kind study to show the link between the T cells and airway muscle.

Authors on the study from Children’s National Hospital include: Deepa Rastogi, M.D., M.S., Changsuek Yon, Ph.D., and David A. Thompson.

You can read the full study, Crosstalk Between CD4+ T Cells and Airway Smooth Muscle in Pediatric Obesity-related Asthma, in the American Journal of Respiratory and Critical Care Medicine.

Abstract Happy 2022 New Year greeting card with light bulb

The best of 2022 from Innovation District

Abstract Happy 2022 New Year greeting card with light bulbA clinical trial testing a new drug to increase growth in children with short stature. The first ever high-intensity focused ultrasound procedure on a pediatric patient with neurofibromatosis. A low dose gene therapy vector that restores the ability of injured muscle fibers to repair. These were among the most popular articles we published on Innovation District in 2022. Read on for our full top 10 list.

1. Vosoritide shows promise for children with certain genetic growth disorders

Preliminary results from a phase II clinical trial at Children’s National Hospital showed that a new drug, vosoritide, can increase growth in children with certain growth disorders. This was the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature.
(2 min. read)

2. Children’s National uses HIFU to perform first ever non-invasive brain tumor procedure

Children’s National Hospital successfully performed the first ever high-intensity focused ultrasound (HIFU) non-invasive procedure on a pediatric patient with neurofibromatosis. This was the youngest patient to undergo HIFU treatment in the world.
(3 min. read)

3. Gene therapy offers potential long-term treatment for limb-girdle muscular dystrophy 2B

Using a single injection of a low dose gene therapy vector, researchers at Children’s National restored the ability of injured muscle fibers to repair in a way that reduced muscle degeneration and enhanced the functioning of the diseased muscle.
(3 min. read)

4. Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National, was selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children.
(4 min. read)

5. New telehealth command center redefines hospital care

Children’s National opened a new telehealth command center that uses cutting-edge technology to keep continuous watch over children with critical heart disease. The center offers improved collaborative communication to better help predict and prevent major events, like cardiac arrest.
(2 min. read)

6. Monika Goyal, M.D., recognized as the first endowed chair of Women in Science and Health

Children’s National named Monika Goyal, M.D., M.S.C.E., associate chief of Emergency Medicine, as the first endowed chair of Women in Science and Health (WISH) for her outstanding contributions in biomedical research.
(2 min. read)

7. Brain tumor team performs first ever LIFU procedure on pediatric DIPG patient

A team at Children’s National performed the first treatment with sonodynamic therapy utilizing low intensity focused ultrasound (LIFU) and 5-aminolevulinic acid (5-ALA) medication on a pediatric patient. The treatment was done noninvasively through an intact skull.
(3 min. read)

8. COVID-19’s impact on pregnant women and their babies

In an editorial, Roberta L. DeBiasi, M.D., M.S., provided a comprehensive review of what is known about the harmful effects of SARS-CoV-2 infection in pregnant women themselves, the effects on their newborns, the negative impact on the placenta and what still is unknown amid the rapidly evolving field.
(2 min. read)

9. Staged surgical hybrid strategy changes outcome for baby born with HLHS

Doctors at Children’s National used a staged, hybrid cardiac surgical strategy to care for a patient who was born with hypoplastic left heart syndrome (HLHS) at 28-weeks-old. Hybrid heart procedures blend traditional surgery and a minimally invasive interventional, or catheter-based, procedure.
(4 min. read)

10. 2022: Pediatric colorectal and pelvic reconstructive surgery today

In a review article in Seminars in Pediatric Surgery, Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National, discussed the history of pediatric colorectal and pelvic reconstructive surgery and described the key advances that have improved patients’ lives.
(11 min. read)

Baby on ventilator

Autonomic markers of extubation readiness in premature infants

Baby on ventilator

Premature infants often require a breathing tube and mechanical ventilation as a mainstay in their therapy. It can be difficult to predict when these patients are ready to come off the ventilator (extubate).

Premature infants often require a breathing tube and mechanical ventilation as a mainstay in their therapy. It can be difficult to predict when these patients are ready to come off the ventilator (extubate). In a study from Pediatric Research, experts from Children’s National Hospital describe a model to predict the success of extubation using markers of autonomic tone (rest and digest versus fight or flight response). This study was led by Suma Hoffman, M.D., neonatologist and co-authored by Adré J. du Plessis, M.B.Ch.B., M.P.H., division chief of Prenatal Pediatrics Institute, Sarah Schlatterer, M.D., prenatal and neonatal neurologist, and Rathinaswamy B. Govindan, Ph.D.

The team deployed a study of 89 infants less than 28 weeks. Heart rate variability (HRV) metrics 24 hours prior to extubation were compared for those with and without extubation success within 72 hours. Receiver-operating curve analysis was conducted to determine the predictive ability of each metric and a predictive model was created.

Conclusions show that extubation success is associated with HRV. The authors demonstrate an autonomic imbalance with low sympathetic and elevated parasympathetic tone in those who failed. α1, a marker of sympathetic tone, was noted to be the best predictor of extubation success especially when incorporated into a clinical model.

Learn more about the study in Pediatric Research.

lung ct scan

With COVID-19, artificial intelligence performs well to study diseased lungs

lung ct scan

New research shows that artificial intelligence can be rapidly designed to study the lung images of COVID-19 patients.

Artificial intelligence can be rapidly designed to study the lung images of COVID-19 patients, opening the door to the development of platforms that can provide more timely and patient-specific medical interventions during outbreaks, according to research published this month in Medical Image Analysis.

The findings come as part of a global test of AI’s power, called the COVID-19 Lung CT Lesion Segmentation Challenge 2020. More than 2,000 international teams came together to train the power of machine learning and imaging on COVID-19, led by researchers at Children’s National Hospital, AI tech giant NVIDIA and the National Institutes of Health (NIH).

The bottom line

Many of the competing AI platforms were successfully trained to analyze lung lesions in COVID-19 patients and measure acute issues including lung thickening, effusions and other clinical findings. Ten leaders were named in the competition, which ran between November and December 2020. The datasets included patients with a range of ages and disease severity.

Yet work remains before AI could be implemented in a clinical setting. The AI models performed comparably to radiologists when analyzing data similar to what the algorithms had already encountered. However, the AI was less valuable when trained on fresh data from other sources during the testing phase, indicating that systems may need to study larger and more diverse data sets to meet their full potential. This is a challenge with AI that has been noted by others too.

What they’re saying

“These are the first steps in learning how we can quickly and accurately train AI for clinical use,” said Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, who led the Grand Challenge Initiative. “The global interest in COVID-19 gave us a groundbreaking opportunity to address a health crisis, and multidisciplinary teams can now focus that interest and energy on developing better tools and methods.”

Holger Roth, senior applied research scientist at NVIDIA, said the challenge gave researchers around the world a shared platform for developing and evaluating AI algorithms to quickly detect and quantify COVID lesions from lung CT images. “These models help researchers visualize and measure COVID-specific lesions of infected patients and can facilitate timelier and patient-specific medical interventions to better treat COVID,” he said.

Moving the field forward

The organizers see great potential for clinical use. In areas with limited resources, AI could help triage patients, guide the use of therapeutics or provide diagnoses when expensive testing is unavailable. AI-defined standardization in clinical trials could also uniformly measure the effects of the countermeasures used against the disease.

Linguraru and his colleagues recommend more challenges, like the lung segmentation challenge, to develop AI applications in biomedical spaces that can test the functionality of these platforms and harness their potential. Open-source AI algorithms and public curated data, such as those offered through the COVID-19 Lung CT Lesion Segmentation Challenge 2020, are valuable resources for the scientific and clinical communities to work together on advancing healthcare.

“The optimal treatment of COVID-19 and other diseases hinges on the ability of clinicians to understand disease throughout populations – in both adults and children,” Linguraru said. “We are making significant progress with AI, but we must walk before we can run.”

Child using inhaler for asthma

Monoclonal antibody reduces asthma exacerbations in urban youth: Q&A with Stephen Teach, M.D.

Child using inhaler for asthmaNew research found that mepolizumab, a monoclonal antibody, decreased asthma flare-ups by 27% in Black and Hispanic children and adolescents who have a severe form of asthma, are prone to asthma attacks, and live in low-income urban neighborhoods.

Stephen Teach, M.D., principal investigator of the IMPACT DC asthma program and co-author of the NIAID-funded Inner City Asthma Consortium-conducted study, offers insight on the importance of this work and what it means for the future of pediatric asthma care at Children’s National Hospital.

What has been the hold-up in this field and how does this work move the field forward?

Urban, Black, and Hispanic children with asthma continue to suffer a disproportionate share of asthma-related morbidity. These findings show that innovative, phenotype-specific therapies are necessary to address their needs.

The study’s investigators were able to document a significant treatment effect in a particularly at-risk population and demonstrated specific gene pathways that were downregulated by treatment with mepolizumab.

What did you find that excites you about this work?

The exciting part of the Inner-City Asthma Consortium’s work has always been that it not only studies whether or not phenotype-driven interventions improve outcomes in high-risk kids, but how those interventions work from a fundamental mechanistic perspective. Those insights drive the science, and the potential clinical applications, forward in an iterative fashion.

How is Children’s National leading in this space?

Investigators from Children’s National continue to be national leaders in developing and testing innovative interventions to address the national disparities in pediatric asthma care and outcomes.

The study, published in the journal The Lancet was co-authored by William Sheehan, M.D., allergist.

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

boy using asthma inhaler

Social determinants of health and asthma morbidity in youth

boy using asthma inhaler

Researchers believe these findings can help develop localized interventions that can improve pediatric asthma in affected communities.

In a study published in the journal Pediatrics, researchers from Children’s National Hospital found that census-tract measures of decreased educational attainment and increased violent crime were associated with increased census-tract rates of pediatric asthma morbidity.

“Knowing these adverse measures of social determinants are associated with increased asthma-related emergency department and hospitalization at-risk rates, may be an opportunity to inform community-based interventions to reduce pediatric asthma morbidity,” says Jordan Tyris, a hospitalist and lead author of the study.

Researchers evaluated data from 15,492 children with asthma, ages 2-17, living in Washington, D.C., from January 2018 to December 2019. The team discovered that living in areas with greater violent crime and less educational achievement were associated with higher rates of hospitalizations and emergency department visits for asthma, in comparison to other social determinants.

The study authors suggest that there may be complex reasons behind this data, noting that violent crime can reflect toxic stress, less education can be associated with less knowledge about health and medicine and that children in these communities may be less likely to have primary care doctors. Researchers believe these findings can help develop localized interventions that can improve pediatric asthma in affected communities and that more research is needed on the drivers of asthma related sickness, including toxic stress, structural racism and access to medical care.

Other study authors include Anand Gourishankar, M.D., Nikita Kachroo AE-C, Stephen Teach, M.D., Kavita Parikh, M.D., all of Children’s National Hospital and Maranda C. Ward, Ed.D., MPH, of George Washington School of Medicine and Health Sciences.

US News Badges

Children’s National named to U.S. News & World Report’s Best Children’s Hospitals Honor Roll

US News BadgesChildren’s National Hospital in Washington, D.C., was ranked No. 5 nationally in the U.S. News & World Report 2022-23 Best Children’s Hospitals annual rankings. This marks the sixth straight year Children’s National has made the 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 sixth year in a row.

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

“In any year, it would take an incredible team to earn a number 5 in the nation ranking. This year, our team performed at the very highest levels, all while facing incredible challenges, including the ongoing pandemic, national workforce shortages and enormous stress,” said Kurt Newman, M.D., president and chief executive officer of Children’s National. “I could not be prouder of every member of our organization who maintained a commitment to our mission. Through their resilience, Children’s National continued to provide outstanding care families.”

“Choosing the right hospital for a sick child is a critical decision for many parents,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings spotlight hospitals that excel in specialized care.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals and recognizes the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News.

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.

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

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

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.