In addition to our regular CRI Activities Update, this month’s Research Focus highlights collaborative work from the team led by Michelle Hernandez, MD, Associate Professor of Pediatrics, UNC Children’s, Associate Medical Director, N.C. Children’s Allergy & Asthma Center.

Activities Update: This month we formed the Pediatric Scholars Program (PSP), a new pediatric Junior Faculty working group. Dr. Smitherman initiated the PSP to fulfill junior faculty requests to have scholarly activity with more senior faculty and content experts, educate members about campus resources that might benefit their scholastic work, and promote junior faculty professional development. The format will be akin to the Pay-it-Forward, Move-it-Forward program, with a monthly luncheon to review a junior faculty member’s project. Melissa Bauserman, MD MPH, has graciously volunteered to kick off our first meeting on Sept. 11 at noon in Bondurant G074.

Also this past month, Toni Darville, MD, presented on behalf of the CRI at the annual School of Medicine (SOM) Research Retreat. She discussed our objectives to increase interactions among Department of Pediatric (DOP) research faculty and UNC researchers outside the DOP who are focused on pediatric diseases, accelerate funding and research output, and advance the health of children in NC and beyond. Launching the CRI in the coming months is timely for several reasons. UNC DOP and SOM have a solid foundation of pediatric disease researchers to move forwarded with collaborative efforts. Next year, CRI administrative support staff and some of our basic science pediatric researchers will move to the renovated Mary Ellen Jones building, creating a centralized physical hub for the CRI. Space for recruitment of additional investigators will be available and the NC Children’s Hospital has identified the CRI as a primary fundraising focus. We will be the first CRI to serve the families of North Carolina.

Finally, a reminder that the Corporate and Foundation Relations team wants to learn about our research endeavors and assist in formation or enhancement of relationships with foundations and industry to generate additional pediatric research funds. If you have not done so already, please let us know before Sept 15 if you want to be part of this conversation.

Research Focus of the MonthTo inform each other of the research interactions in pediatrics, and in the spirit of CRI’s mission to promote collaboration, each CRI update will continue to highlight different investigators’ collaborative efforts. Below is a summary on the collaborative research from the team led by Michelle Hernandez, MD, Associate Professor of Pediatrics, UNC Children’s, Associate Medical Director, N.C. Children’s Allergy & Asthma Center.

Michelle Hernandez, MD

The Hernandez Lab is a prime example of the advances that can be made in pediatric research when collaboration among UNC Children’s researchers and clinicians is infused into a team’s working structure. Dr. Hernandez and her team have embarked on a multi-pronged effort to find anti-inflammatory treatments that work quickly and effectively to treat acute asthma exacerbations.

Asthma is an increasingly common chronic illness with staggering costs. The Asthma and Allergy Foundation of America estimates that annual asthma-related health care costs total about $56 billion, and more than half of the overall asthma-related costs were attributed to inpatient hospitalization. There is an even greater cost to children with asthma – one of the leading chronic diseases of childhood, asthma contributes to more than 10.5 million missed school days for children ages 5-17 every year. Allergen exposure and viral infection are among the most common triggers for asthma exacerbations.

Currently, there is an urgent need for anti-inflammatory treatments that work quickly and effectively in acute asthma exacerbations. While corticosteroids are the mainstay for treating the inflammatory component of asthma exacerbations, regardless of the trigger, they have an initial lag period of four to six hours or more for therapeutic effect. That lag time limits their benefit in the acute setting. There is also concern about immune and growth suppression, and corticosteroids are often ineffective in treating the neutrophilic component of airway inflammation seen with viral infection and allergen-induced airway inflammation. There is also a notable lack of effective mucolytic treatments for asthma, even though mucus plugging is a hallmark of severe and fatal asthma exacerbations.

Dr. Hernandez’s team has worked across UNC Health Care and with other area researchers to help identify human models of innate immune activation in order to target inflammatory triggers and reduce asthma exacerbations, help asthma patients better manage their chronic illness, and train the next generation of asthma researchers. In doing so, Dr. Hernandez and her team have developed well-characterized models of innate immune activation by using inhaled endotoxin (lipopolysaccharide), ozone, and allergen challenge to induce neutrophilic airway inflammation, airway hyperreactivity, and mucus production in human volunteers with asthma. Using these well-characterized models, they have targeted inflammatory responses from a variety of agents in early phase clinical studies and have found promise for non-corticosteroid agents in alleviating features of asthma exacerbations.

In 2015, Dr. Hernandez, along with David Peden, MD, in the Center for Environmental Medicine, Asthma, & Lung Biology (CEMALB) and Haibo Zhou, PhD, in the Department of Biostatistics at the Gillings School of Public Health, published a NIH study that examined the safety of the IL-1 receptor antagonist (IL-1RA), anakinra, to suppress acute innate immune system neutrophil responses to endotoxin challenge. The collaborative study found that anakinra significantly reduced airway neutrophilia and reduced LPS-induced markers of inflammation (IL-1b, IL-6, IL-8) compared to placebo. These findings make anakinra a potential therapeutic candidate for treating asthma with neutrophil predominance.

Dr. Hernandez’s team is also working with the U.S. Environmental Protection Agency, and with N.C. State University’s Advanced Self-Powered Systems of Integrated Sensors and Technologies (ASSIST) center to develop mobile health-focused technology and tools that help asthma patients manage their care and reduce asthma exacerbations. Currently, the group is field-testing an innovative hand-held VitalFlo spirometer and wearable sensors that can detect changes in air pollution and transmit data to a cell phone and data center. In addition, her collaboration with Delesha Carpenter, PhD, MSPH, in the UNC Eshelman School of Pharmacy, led to the development of mobile health (mHealth) interventions centered on user preferences to create technology-based interventions for youth with asthma.

Dr. Hernandez’s lab is also looking ahead to train the next generation of researchers to address ongoing challenges in treating and curing asthma in children. Allison Burbank, MD, Assistant Professor of Pediatrics, is examining how obesity impacts the efficacy of mainstay asthma therapies, while Amika Sood, MD, Allergy Immunology Fellow, is leading research to create models of rhinovirus infection, a common trigger for asthma exacerbations, to develop therapies that target virally induced airway inflammation without disrupting anti-viral function. Drs. Burbank, Peden, and Hernandez recently published a proof-of-concept study in the Journal of Allergy Asthma, and Immunology on the effects of a 2-week treatment with the anti-inflammatory/antioxidant, gamma tocopherol (a vitamin E isoform), in patients with mild asthma. This isoform of Vitamin E is the one most commonly found from dietary sources, such as nuts. When compared to control, supplementation with gamma tocopherol reduced inflammatory markers of asthma (ie, sputum eosinophils and mucins) and acute airway response to inhaled LPS. Also, the results observed with gamma tocopherol treatment were similar to that previously published with inhaled fluticasone propionate. Implications from these findings are that airway inflammation and mucous production/clearance resulting from asthma may respond to treatment with gamma tocopherol through non-steroid-related therapies; further largescale studies are warranted on the efficacy and long-term safety of gamma tocopherol in the treatment of patients with more severe asthma.

For more information on Dr. Hernandez’s team’s research, read more about their study of the IL-1 receptor anakinra to suppress asthma with neutrophil predominance.

Links to publications:

https://www.ncbi.nlm.nih.gov/pubmed/28736267

https://www.ncbi.nlm.nih.gov/pubmed/?term=25195169