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illustration of lungs with virus

Segmenting viral bronchiolitis patients to better predict clinical outcomes

illustration of lungs with virus

By evaluating viral bronchiolitis patients at first presentation and categorizing them based on clinical phenotype, the researchers were able to better predict outcomes and disease progression patterns.

Researchers from Children’s National Hospital have recently published a pilot study of children with viral bronchiolitis. By evaluating viral bronchiolitis patients at first presentation and categorizing them based on clinical phenotype, the researchers were able to better predict outcomes and disease progression patterns. Nasal airway cytokine levels were also measured to assess the underlying airway immunobiology of different clinical phenotypes. The researchers believe this novel subdivision of viral bronchiolitis patients based on a robust combination of clinical and molecular assessment can help lead to more individualized care and better patient outcomes.

Viral bronchiolitis is broadly used to group together infants with first-time severe viral respiratory infection, which is the most common cause of early life sick visits and hospitalizations worldwide. However, viral respiratory infections can vary significantly in clinical manifestations, which has raised concern among experts that the use of viral bronchiolitis as a catchall term may be compromising patient care. Children’s National researchers hypothesized that a novel segmentation technique of viral bronchiolitis patients by phenotype at first episode could provide better outcome prediction. In addition, lung X-rays and nasal cytokine profiles could help illuminate the underlying airway disease processes that drive the phenotypical differences observed at bedside.

The study examined 50 children ≤ 2 years old, including 41 patients admitted at Children’s National with PCR-confirmed viral respiratory infection and 9 controls. Researchers examined clinical features at presentation by reviewing each patient’s electronic medical record. Key parameters served as the basis for patient segmentation into three phenotypical groups: hypoxemia, wheezing and mild phenotypes. Patients in the hypoxia group (n = 16) were characterized by their need for supplemental oxygen; patients in the wheezing phenotype (n = 16) were distinguished by wheezing or subcostal retractions and patients in the mild phenotype (n = 9) displayed persistent respiratory symptoms but not hypoxia, wheezing or subcostal retractions. Chest x-rays further revealed that patients in the hypoxia phenotype displayed significantly more lung opacities than the other phenotypes.

As hypothesized, the three phenotype groups displayed distinct clinically relevant outcomes. Patients in the hypoxia group had more severe clinical symptoms at presentation and were significantly more likely to require prolonged hospitalization and pediatric intensive care unit (PICU) settings for treatment. Patients in the wheezing phenotype had shorter hospital stays but were significantly more likely to make a respiratory sick visit after initial discharge, with 69% coming back to the hospital with the same symptoms. Patients in the mild phenotype had the shortest hospital stays and did not require transfer to the PICU.

Nasal cytokine profiles were also assessed for all study subjects. Controls had lower cytokine levels than patients, with no significant difference between phenotype groups. However, wheezing patients with ≥1 recurrent respiratory sick visit had higher nasal levels of type 2 cytokines IL-13 and IL-4, consistent with the pathobiology of allergic asthma. This result adds support for the potential of initial sub-setting in guiding timely intervention.

The researchers hope that the strong results of their pilot study will guide clinicians to revise current practices regarding viral bronchiolitis and personalize care of viral respiratory illnesses from first presentation in order to improve outcomes. Study author and Children’s National pulmonologist Maria Arroyo, M.D., says, “if we can prevent these patients from coming [back] to the hospital just by doing a clinical evaluation the first time that they present with [viral respiratory infection]…that would be very impactful.”

The associated article, “Phenotypical Sub-setting of the First Episode of Severe Viral Respiratory Infection Based on Clinical Assessment and Underlying Airway Disease: A Pilot Study,” was published April 2, 2020 in Frontiers in Pediatrics. Notable authors include Maria Arroyo, M.D., Kyle Salka, M.S., and Gustavo Nino, M.D., M.S.H.S., D.A.B.S.M.

electronic cigarette dispenser with different flavors of nicotine

Extreme difficulty breathing and swallowing linked to teen’s vaping?

electronic cigarette dispenser with different flavors of nicotine

After a teen was transferred to Children’s National Hospital suffering from severe difficulty breathing and swallowing, a multidisciplinary team continued the detective work and surmises that vaping was to blame for her unusual symptoms.

A teenage girl with no hint of prior asthma or respiratory illness began to feel hoarseness in her throat and a feeling that she needed to clear her throat frequently. Within a few weeks, her hoarseness and throat-clearing worsened with early morning voice loss and feeling as if food were lodged in her throat. She started having trouble swallowing and began to avoid food all together.

Her pediatrician prescribed loratadine for suspected allergies to no avail. Days later, an urgent care center prescribed a three-day course of prednisone. For a few days, she felt a little better, but went back to feeling like she was breathing “through a straw.” After going to an emergency room with acute respiratory distress and severe difficulty swallowing, staff tried intravenous dexamethasone, ampicillin/sulbactam, and inhaled racemic epinephrine and arranged for transfer.

When she arrived at Children’s National Hospital, a multidisciplinary team continued the detective work with additional testing, imaging and bloodwork.

Examining her throat confirmed moderate swelling and a partially obstructed airway draped with thick chartreuse-colored mucus. The teen had no history of an autoimmune disorder, no international travel and no exposure to animals. She had no fever and had received all her scheduled immunizations.

“With epiglottitis – an inflammation of the flap found at the base of the tongue that prevents food from entering the trachea – our first concern is that an underlying infection is to blame,” says Michael Jason Bozzella, D.O., MS, a third-year infectious diseases fellow and lead author of the case report published Feb. 5, 2020, in Pediatrics. “We tested her specimens in a number of ways for a host of respiratory pathogens, including human rhino/enterovirus, respiratory syncytial virus, influenza, Epstein-Barr virus, Streptococcus and more. All negative. We also looked for more atypical infections with bacteria, like Arcanobacterium, Mycoplasma and Gonorrhea. Those were all negative as well,” Dr. Bozzella adds.

She slowly improved during a seven-day initial hospital stay, though soon returned for another six-day hospital stay after it again became excruciatingly painful for her to swallow.

Every throat culture and biopsy result showed no evidence of fungal, bacterial or viral infection, acid-fast bacilli or other malignancy. But in speaking with doctors, the teen had admitted to using candy-and fruit-flavored e-cigarettes three to five times with her friends over the two months preceding her symptoms. The last time she vaped was two weeks before her unusual symptoms began.

According to the Centers for Disease Control and Prevention, 2,668 people in the U.S. have been hospitalized for e-cigarette or vaping product use-associated lung injury, as of Jan. 14, 2020. The Children’s National case report’s authors say the increasing use of vaping products by teenagers highlights the potential for unknown health risks to continue to grow.

“This teenager’s use of e-cigarettes is the most plausible reason for this subacute epiglottitis diagnosis, a condition that can become life-threatening,” says Kathleen Ferrer, M.D., a hospitalist at Children’s National and the case report’s senior author. “This unusual case adds to a growing list of toxic effects attributable to vaping. While we normally investigate infectious triggers, like Streptococci, Staphylococci and Haemophilus, we and other health care providers should also consider e-cigarettes as we evaluate oro-respiratory complaints.”

In addition to Drs. Bozzella and Ferrer, Children’s National case report co-authors include Matthew Allen Magyar, M.D., a hospitalist; and Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases.

Michael Tsifansky

Lung transplant expert Michael Tsifansky, M.D., F.A.A.P., joins Children’s

Michael Tsifansky

Earlier this year Michael Tsifansky, M.D., F.A.A.P., joined Children’s National Hospital as an attending physician in the Cardiac Intensive Care Unit and in the Division of Pulmonology and Sleep Medicine. He brings to Children’s National a unique mix of expertise in critical care and pulmonary medicine. That passion for these two subspecialties has also made him one of the country’s leading experts in lung transplant procedures and the recovery from them.

Dr. Tsifansky shared more information about caring for patients with complex lung diseases, especially those with end-stage lung disease. He outlines the patient population for pediatric lung transplants and the arduous process patients endure while waiting for a transplant, undergoing this major procedure, and then recovering from it.

What types of patients undergo lung transplant surgeries?

Lung transplantation in children is indicated when the following criteria are met:

  • End-stage lung disease
  • No reasonable alternative to the established diagnosis
  • No medical or surgical alternative to the current course of treatment
  • No other organ failure
  • Stable social environment

Could you describe the surgery process?

Pediatric lung transplantation may be performed on cardiopulmonary bypass, on extracorporeal membrane oxygenation (ECMO) or off extracorporeal cardiopulmonary support (ECS). The donor’s lungs are kept chilled prior to transplantation and should be transplanted within six to eight hours after removal from the donor. The donor’s main-stem bronchi and pulmonary arteries are connected to those of the recipient, and the donor’s pulmonary venous drainage is connected to the recipient’s left atrium using the donor’s left atrial roof tissue. This procedure typically takes six to eight hours.

Could you describe the recovery process?

Typically, pediatric lung transplant recipients are extubated and encouraged to sit up four to six hours after the transplant procedure and walk soon afterward. It is important that they be out of bed and moving as soon as possible, and our colleague from Rehabilitation Services (physical and occupational therapists and rehabilitation physicians) will be working with the children toward these goals. After transplantation, pediatric patients will be given discharge instructions with individualized guidelines for a healthy lifestyle. Patients should return to near-normal life approximately three to six months after transplantation.

How long does the recovery process take?

The patient will remain hospitalized for 11-14 days following surgery for acute rehab, titration of antirejection meds and initial healing.

You’ve mentioned that it’s important for transplant patients to get moving as part of recovery. When can a patient begin walking again?

Lung recipients will be assisted into a chair soon after the transplant. Within the first 24-36 hours, the patient is encouraged to take short walks, increasing the distance each day. A physical therapist will work with the patient during their hospitalization to meet their goals. We also encourage patients to exercise on the treadmill regularly while hospitalized. By the time the patient is ready to go home, he or she will be able to easily move around by themselves and do most of their care without assistance. They feel so much better than before transplant and have so much energy that we almost always have to gently limit their activity for a short while to allow their chest incision to heal properly.

What do you see as the next step in pulmonary care for end stage lung disease at Children’s National Hospital?

The development of a pediatric-specific lung transplant and respiratory failure program is the natural extension of the hospital’s cystic fibrosis program, heart transplant program and programs in pulmonary hypertension, bronchopulmonary dysplasia and extracorporeal membrane oxygenation for respiratory failure.

At present, there is no local option for a pediatric-specific program that can perform the transplant and provide the necessary comprehensive wrap-around services for patients in infancy up to age 18. As a top children’s hospital, Children’s National is uniquely positioned to provide the highest level of pediatric-specific care to this patient population and allow patients and their families to spend more time at home while undergoing this and other lifesaving treatments.

Dr. Tsifansky hopes to launch a comprehensive pediatric lung transplant and respiratory failure program at Children’s National in the very near future. Stay tuned for future developments from this area.

Steven Hardy

Steven Hardy, Ph.D., awarded prestigious NIH grant for sickle cell research, career development

Steven Hardy

Steven Hardy, Ph.D., a pediatric psychologist in the Center for Cancer and Blood Disorders at Children’s National, has been awarded a K23 Mentored Patient-Oriented Research Career Development Award by the National Heart, Lung, and Blood Institute (NHLBI) in recognition of his progress toward a productive, independent clinical research career. National Institutes of Health (NIH) Mentored Career Development Awards are designed to provide early career investigators with the time and support needed to focus on research and develop new research capabilities that will propel them to lead innovative studies in the future.

Dr. Hardy, who has worked at Children’s National since 2013, specializes in the emotional, behavioral and cognitive aspects of children’s health, with a particular emphasis on evaluating and treating psychological difficulties among children with cancer or sickle cell disease. With the K23 award, he will receive nearly $700,000 over a five-year period, which will provide him with an intensive, supervised, patient-oriented research experience. The grant will support Dr. Hardy’s time to conduct research, allow him to attend additional trainings to enhance research skills, and fund a research project titled “Trajectory of Cognitive Functioning in Youth with Sickle Cell Disease without Cerebral Infarction.”

Many children with sickle cell disease (SCD) also have intellectual challenges which stem from two primary pathways – stroke and other disease-related central nervous system effects. While stroke is a major complication of SCD, the majority of children with SCD have no evidence of stroke but may still exhibit cognitive functioning challenges related to their disease. Such cognitive difficulties have practical implications for the 100,000 individuals in the SCD, as 20-40% of youth with SCD repeat a grade in school and fewer than half of adults with SCD are employed. Dr. Hardy’s project will focus on understanding the scope and trajectory of cognitive difficulties in children with SCD without evidence of stroke, as well as the mechanisms that precipitate disease-related cognitive decline. The study will characterize temporal relationships between biomarkers of SCD severity and changes in cognitive functioning to inform future development of risk stratification algorithms to predict cognitive decline. Armed with the ability to predict cognitive decline, families will have additional information to weigh when making decisions and providers will be better able to intervene and tailor treatment.

Nikki Gillum Posnack

What are the health effects of plastics?

Nikki Gillum Posnack

Nikki Posnack, Ph.D., assistant professor at the Children’s National Heart Institute, is an early-stage investigator examining the impact plastic chemical exposure has on the developing hearts of newborns and young children.

For newborns or children in the pediatric intensive care unit, plastic tubing is part of daily life. It delivers life-sustaining blood transfusions, liquid nutrition and air to breathe. But small amounts of the chemicals in the plastic of this tubing and other medical devices can leak into the patient’s bloodstream. The potential effects of these chemicals on the developing hearts of newborns and very young children are not well understood.

One researcher, Nikki Posnack, Ph.D., an assistant professor at the Children’s National Heart Institute, aims to change that and shares her early insights, funded by the National Center for Advancing Translation Science (NCATS), in an NCATS news feature.

“While plastics have revolutionized the medical field, we know chemicals in plastics leach into the body and may have unintended effects,” Posnack said. “The heart is sensitive to toxins, so we want to look at the effect of these plastics on the most sensitive patient population: kids who are recovering from heart surgery and already prone to cardiac complications.”