Pulmonology & Lung Surgery

baby with with bronchopulmonary dysplasia

A team approach to complex bronchopulmonary dysplasia

“By the time a baby is diagnosed with bronchopulmonary dysplasia, families have already had a long journey with prematurity in the neonatal intensive care unit (NICU),” says Hallie Morris, M.D., neonatologist and lead of the Complex Bronchopulmonary Dysplasia (BPD) Program at Children’s National Hospital. “To be able to have a team that is focused on the holistic health of their child in the context of this diagnosis makes a world of difference to these families.”

The big picture

Some premature infants with BPD experience more severe respiratory disease with comorbidities associated with their underlying disease processes, but also factors related to their lengthened intensive care unit (ICU) stay. This includes delayed development with neurodevelopmental impairment, ICU delirium, pulmonary hypertension, airway disease, gastroesophageal reflux disease, feeding difficulties, retinopathy of prematurity and more.

The Complex BPD Program at Children’s National encompasses a group of specialists dedicated to improving the care of infants with BPD and other chronic lung disease of infancy. BPD places extreme demands on families. Education is a critical component for families and our team works to make sure they are well informed, have realistic expectations and understand their care plan.

What they’re saying

  • “Our program is unique in that it has the ability to follow the patient for several months in the NICU as well as after discharge,” says Maria Arroyo, M.D., pulmonologist and co-lead of the Complex BPD Program at Children’s National. “This includes a subacute facility where some of our NICU patients transfer to for continued respiratory weaning and rehabilitation with parent education and outpatient visits once families are home.”
  • “Since this program was created, we have improved patient care and outcomes with this interdisciplinary approach,” says John Berger, M., medical director for the Pulmonary Hypertension Program at Children’s National. “We expect that with our consistent and personalized care, patients will continue have better overall outcomes, less readmissions and improved neurodevelopmental outcomes.

Learn more about the Complex BPD Program.

person pouring pills from bottle to hand

Therapeutic antibiotics associated with reductions in microbial diversity in CF

person pouring pills from bottle to hand

Researchers found that both insufficient beta-lactam pharmacokinetics (PK) and broad-spectrum antibiotics were associated with a greater decrease in species richness at the end of antibiotic therapy compared to pulmonary exacerbations onset.

There are more than 70,000 children and adults living with cystic fibrosis (CF) worldwide. Those with this progressive disease frequently suffer from recurrent episodes of lung infection and inflammation called pulmonary exacerbations.

In a new observational study led by Andrea Hahn, M.D., infectious diseases specialist at Children’s National Hospital, researchers found that both insufficient beta-lactam pharmacokinetics (PK) and broad-spectrum antibiotics were associated with a greater decrease in species richness at the end of antibiotic therapy compared to pulmonary exacerbations onset.

In prior studies evaluating the association between beta-lactam PK, insufficient beta-lactam PK was associated with reduced short-term decreases in microbial diversity compared to sufficient beta-lactam dosing. In this study researchers found that insufficient beta-lactam PK was associated with a greater short-term decrease in microbial diversity.

Dr. Hahn’s team also found that an increased presence of beta-lactam antibiotic resistance genes was associated with lower microbial diversity and lower lung function.

These studies suggest that community-level antibiotic resistance, rather than the resistance patterns of the most prevalent bacteria identified in cultures, may serve as a useful predictor of lung function recovery in individuals with cystic fibrosis (CF). This finding may aid clinicians in selecting the most effective antibiotics to treat pulmonary exacerbations in CF patients, thus enhancing their clinical outcomes.

Read the full study in Nature’s Scientific Reports.

Authors on the study from Children’s National Hospital include Andrea Hahn, M.D., M.S., Aszia Burrell, Hollis Chaney, M.D., Iman Sami-Zakhari, M.D., Anastassios Koumbourlis, M.D., M.P.H., and Robert J. Freishtat, M.D., M.P.H.

boy using spirometer

Hydroxyurea initiation improves spirometry results in children with sickle cell anemia

boy using spirometer

Hydroxyurea therapy may help preserve lung function over time in children with sickle cell anemia.

Children’s National researchers participated in a recent study suggesting that the use of hydroxyurea (HU) therapy in children with sickle cell anemia (SCA) may help preserve lung function over time.

Sickle cell disease is associated with various pulmonary complications, including reactive airways, acute chest syndrome (ACS), pulmonary fibrosis and pulmonary arterial hypertension, which can lead to increased morbidity and mortality. Lung function tends to decline over time in individuals with SCA, and a more irreversible restrictive pathology develops with age and increasing respiratory complications.

Hydroxyurea is a disease-modifying therapy that has been shown to lower the rates of several complications of SCD, such as ACS and painful vaso-occlusive crises. It also might help lessen the severity of airway hyperreactivity in children.

This study provides evidence that hydroxyurea therapy may have a positive impact on pulmonary function in children with SCA, which could be of interest to doctors treating this patient population. By slowing the decline in lung function, hydroxyurea therapy may help reduce the risk of pulmonary complications and improve the overall health outcomes of children with SCA.

You can read the full study, Spirometric Changes After Initiation of Hydroxyurea in Children With Sickle Cell Anemia, in the Journal of Pediatric Hematology/Oncology.

Authors on the study from Children’s National Hospital include Dinesh Pillai, M.D., Deepika Darbari, M.D., and Anastassios Koumbourlis, M.D., M.P.H.

girl looking at medicine bottle

Effect of antibiotics on microorganisms and lung function in children with CF

girl looking at medicine bottle

The study suggests that the use of antibiotics to treat PEx in children with CF may not be as harmful to the airway microbiome as previously believed.

Cystic fibrosis (CF) is a disease that affects many people, especially children. Pulmonary exacerbations (PEx) are common in people with CF and can cause a decline in lung function. These PEx are often treated with antibiotics, but little is known about how antibiotics affect the airway microbiome (the collection of microorganisms in the lungs) of people with CF over time.

Experts from Children’s National Hospital took part in a recent study which looked at how the airway microbiome and lung function of children with CF changed over the course of a year following an initial PEx. The study found that the diversity of the airway microbiome increased over the year despite a decrease in lung function associated with repeated PEx events requiring antibiotic therapy. This suggests that repeated treatment with antibiotics may not have a negative impact on the overall diversity of microorganisms in the lungs.

It is important for pediatricians to understand how antibiotics affect the airway microbiome in children with CF because it can help them make more informed decisions about treatment options. The findings of this study suggest that the use of antibiotics to treat PEx in children with CF may not be as detrimental to the airway microbiome as previously thought. This information can help pediatricians provide better care for children with CF and ultimately improve their overall health outcomes.

You can read the full study, Impact of Antibiotics on the Lung Microbiome and Lung Function in Children With Cystic Fibrosis 1 Year After Hospitalization for an Initial Pulmonary Exacerbation, in Open Forum Infectious Diseases.

Authors on the study from Children’s National Hospital include Zaina Inam, M.D., Aszia Burrell, Hollis Chaney, M.D., Iman Sami-Zakhari, M.D., Anastassios Koumbourlis, M.D., M.P.H., Robert J. Freishtat, M.D., M.P.H., and Andrea Hahn, M.D., M.S.

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 surgery, gastroenterology 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.