Bridgette L. Jones, MD, MSCR
Marion Merrell Dow Endowed Chair in Pediatric Clinical Pharmacology; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Education Associate Professor of Pediatrics, University of Kansas School of Medicine
Full BiographyQ&A with Dr. Bridgette Jones
Recently, Bridgette Jones, MD, MSCR, Allergy, Asthma, and Immunology and Pediatric Clinical Pharmacology, received a five-year, $2.4 million R01 grant from the National Institutes of Health for research on predicting treatment response in children with asthma titled, “A Histamine Pharmacodynamic Biomarker to Guide Treatment in Pediatric Asthma.”
Here, Dr. Jones shares more about this important grant, and what she hopes to accomplish.
What prompted you to research this topic?
There is a critical need for tools that predict treatment response for asthma therapies in children. Children who require daily asthma treatment with a controller medication, such as an inhaled steroid, are defined as having persistent asthma. Approximately 60% of children with asthma in the U.S. have persistent disease.
Variability in treatment response to standard guideline-supported medications (e.g., inhaled steroids, leukotriene modifiers, monoclonal antibodies) exists among children with persistent asthma. Currently utilized clinical markers, such as markers in the blood or lung, do not predict treatment response well or require invasive procedures that are not feasible to conduct widely in children with asthma.
Why are clinical markers, such as markers in the blood or lung, not good predictors of treatment response?
We really don’t have great objective biomarkers or tools to tell us when we’re supposed to use specific medicines in treating asthma. A lot of medicines, such as biologic therapies or monoclonal antibody therapies, are broadly recommended for patients who have an “allergic phenotype.” However, identification of this phenotype is not consistently defined. Some may use eosinophil count; some may use IgE levels; or some patients may have a general diagnosis of allergies. Sometimes that information may predict who could benefit from those medicines, but many times they do not. There is a need for more specific objective biomarkers to better direct treatments.
For my study, I’m looking at antihistamines, an older and commonly used group of medications that we know have benefit in patients with allergies and likely in those with allergic asthma. However, antihistamines are not part of standard asthma therapies because they haven’t been studied using objective biomarkers to truly identify which patients may receive the most benefit from them as part of their standard asthma regimen.
What is the HILD tool and how is it thought to predict treatment response?
The novel part of our study is using histamine response as a biomarker to predict the patient’s response with HILD, or histamine iontophoresis with laser Doppler, a non-invasive technique where we administer a histamine gel to the superficial skin of the arm, then measure blood flow response at the site using a small laser ultrasound probe.
The probe measures dynamic changes in blood flow, including an increase that can occur with a histamine challenge. This is a much more objective way to gauge histamine response compared to traditional allergy testing, or a skin prick test, where the patient’s skin is scratched with a small device that applies histamine to the skin and it is absorbed, causing a wheal-and-flare response (raised red area) that is measured manually with a ruler-type device. In comparison, HILD allows a fixed dose of histamine to be applied, in addition to obtaining a dynamic and more accurate measurement of response and overall reduces variability from human error or differences in application and measurement.
Will this research help solve a current problem or better patient outcomes?
It’s not possible to provide the most effective treatments for all asthma patients without tools that are able to better define asthma phenotypes and predict which medications may work best before a patient tries them. Our research hypothesizes that HILD can predict response to an antihistamine treatment in children with allergic asthma.
In addition, the study will determine if HILD, combined with clinical markers in the blood and lungs, can provide an even better prediction of who responds to antihistamines for treatment of allergic-type asthma.
Has this topic, including differences in asthma pathophysiology and treatment response between African-American and Caucasian children, been studied before?
We know that the underlying drivers and resultant pathophysiology of asthma is often different between African American/Black children and White children. These differences likely occur due to structural and systemic racism and inequities which disproportionately impact the overall health of Black children. This study will not only characterize the differences in observed phenotype between Black and White children, but also will identify if there are actual differences in how Black and White children respond to antihistamine treatments due to these differing asthma phenotypes.
Previously, there have been studies showing that African-American/Black children are more likely to have an allergic phenotype, and they are more likely to have severe disease. Another recent study showed that Black children overall had a superior response to inhaled corticosteroids. In a Letter to the Editor published in the New England Journal of Medicine Jan. 23, 2020, from myself and Susamita Kesh, MD, we wrote in response to this study that historically there has been an overall lack of inclusion of Black and Hispanic participants in asthma-related clinical trials. In our search of ClinicalTrials.gov, we found that though Black and Hispanic children suffer disproportionately from asthma, they are poorly represented or not represented at all in clinical trials of monoclonal antibody therapies for asthma. Owing to the lack of racial and ethnic diversity in clinical trials involving patients with asthma, these data are not fully informative to support effective treatment guidelines for all children. Our goal for this research is to include these patients, ultimately better informing treatment decisions related to asthma and antihistamines.
How is the study designed?
Antihistamines are standard therapies for allergies and commonly used, so we know a lot about them. They’re generally safe and inexpensive, so if we could identify which patients would benefit from just adding a simple antihistamine to their medication regimen, that could go a long way toward improving outcomes and the overall impact of asthma.
This study will enroll African-American/Black and White children who have uncontrolled allergic asthma. These patients will already be on inhaled steroids for their asthma, and they will proceed to a clinical trial of an antihistamine added to their standard asthma therapy. We will look at whether their asthma is improved with the addition of the antihistamine and we will use HILD combined with clinical markers in the blood and lungs to see if we can provide an even better prediction of who responds to antihistamines for treatment of allergic-type asthma.
How will learnings from this research help patients? What could it mean for them?
My goal is to really understand why kids have asthma, why some kids do poorly, or some kids have really bad asthma that we can’t get under control, no matter what therapies we put them on. We need to try to develop a way to guide treatment to decrease the risk of medications that aren’t as effective for certain kids. This is especially true when you think of a growing, developing child. For me, that really is the ultimate goal—to get a patient to the best therapy as fast as possible without exposing them to treatments that don’t work for them.
How could this data help change how physicians treat their patients with persistent asthma?
Asthma impacts quality of life for our patients and their families. It’s not just that the patient is having an asthma flare-up, but it prevents kids from going to school, playing sports, and makes them miserable. Parents have to miss work or find child care for other children so they can take their child with asthma to the emergency room or to doctor appointments. Asthma impacts the quality of life of many people. If we could identify the best treatments for kids utilizing reliable biomarkers, and avoid this trial and error period with medications, that would help guide physicians to the right treatment for their patient, not only improving clinical outcomes, but also quality of life for patients and their families.
Is Children’s Mercy one of several sites involved in this study?
This is a single-site study that will be conducted only at Children’s Mercy. We will recruit 300 children from the Kansas City area to participate in this study over a four-to-five-year time frame.