Metabolomics Brings Precision Medicine for Severe Asthma

From discovery of a new type of asthma driver to assessing personalized risk with using inhaled corticosteroids, metabolomics research brings precision medicine approaches for severe asthma

An international study has led to a new metabolomic discovery that could improve precision medicine treatments for severe asthma. This study takes us to Australia and Sweden where researchers have identified a possible asthma driver that can be detected using a simple urine test.

Even though more than 260 million people worldwide live with asthma, according to the World Health Organization, identifying asthma when it is severe can be complicated. Treatments are often unsuccessful before asthma is recognized. Additionally, severe asthma is difficult to treat because of the knowledge gap in what causes it. These are some of the factors spurring scientists to test new approaches to asthma research, clinical laboratory testing, and treatment.

The recent research, led by senior lecturer Stacey Reinke, PhD, at Edith Cowan University in Australia, and Craig Wheelock, PhD, Associate Professor of Biochemistry at Karolinska Institutet in Sweden, was published in the European Respiratory Journal. As part of the U-BIOPRED study, the work identified a specific class of metabolite, called carnitine. What’s new about this study is that researchers found carnitine to be significantly lower in patients with severe forms of asthma.

Stacey Reinke, PhD (left), and Craig Wheelock, PhD (right), are studying carnitine as a possible driver of severe asthma. (Photos: Edith Cowan University, Karolinska Institutet)

Urinary Metabolome for Understanding Asthma Triggers and Controls

“To identify and develop new treatment options, we first need to better understand the underlying mechanisms of the disease,” Reinke explained in an Edith Cowan University statement. “In this case, we were able to use the urinary metabolome of asthmatics to identify fundamental differences in energy metabolism that may represent a target for new interventions in asthma control.

“Any biochemical changes in the lungs can enter the blood stream, and then be excreted through the urine,” Reinke said. One of the key benefits of this new research is the ability to easily test how asthma is affecting the lungs.

Metabolomics involves the study of small molecules that have metabolic roles. This study measured carnitine which is important to immune health and generating energy. The researchers found that in patients with severe asthma, specifically, carnitine levels were abnormally low. This provided a method of distinguishing severe asthma from mild to moderate asthma. Additionally, the finding provides precision medicine researchers with a new piece of the puzzle as to what may cause severe asthma.

Metabolomics for Evaluating Personalized Risk in Asthma Treatments

The study into carnitine is not the first time that metabolomics has provided asthma clinicians and researchers with valuable insights. In March 2022, a precision medicine study used metabolomics to evaluate the personalized risk of certain asthma treatments. In this example, researchers from Brigham and Women’s Hospital and the University of Cambridge evaluated how people with asthma were affected by inhaled corticosteroids, a class of medications commonly used to treat asthma.

Using a metabolomic approach, the researchers found that people with certain genetic variants could be more at risk for adrenal suppression when using corticosteroids, according to an article published in the American Journal of Managed Care (AJMC). Adrenal suppression is harmful because it interferes with the production of certain hormones and their important functions.

The related article, published in Nature, raised the question of whether a metabolomic analysis should be performed on each asthma patient before using corticosteroids to see if there is a risk of suppression of normal adrenal function. Research into the implications of these new findings is ongoing but highlights the important role that metabolomics is playing in the development of precision medicine treatments for asthma.

Improving Analysis of Metabolites

In 2015, metabolomics was characterized as an emerging field. To advance the field, the Common Fund Metabolomics Program was initiated in 2012 by the National Institutes of Health (NIH). The program was meant to increase the national capacity for metabolomics and to catalyze research by creating new tools, infrastructure, and data to fuel the field of study. A major goal of the metabolomics program is to discover new ways to diagnose diseases by improving the analysis of metabolites, which are molecules produced from chemical reactions that occur in cells.

Healthcare leaders can anticipate that metabolomics will play an increasingly important role in diagnosing and treating asthma, as testing metabolites offers a convenient alternative to more complicated lung tests. The precision medicine applications of metabolomics will enable more personalized treatment that improves the effectiveness of interventions.

—Caleb Williams