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UPMC Children’s Pediatric Pulmonary Medicine Team Co-Authors Important Commentary on Needed Research for T2-Low Asthma in The Lancet Respiratory Medicine

February 29, 2024

UPMC Children’s Hospital of Pittsburgh Division of Pediatric Pulmonary Medicine faculty recently published and important commentary on "Type 2-Low Asthma In School-Aged Children: Unacknowledged And Understudied.” The commentary was published in the December 2023 issue of The Lancet Respiratory Medicine.

Co-authoring the perspective from UPMC Children’s was first author, Pooja E. Mishra, MD, who is currently a pediatric pulmonary medicine fellow at UPMC Children’s and the University of Pittsburgh School of Medicine, and UPMC Children’s Pediatric Pulmonary Medicine division chief, Juan C. Celedón, MD, DrPh, ATSF.

Joining Drs. Mishra and Celedón on the paper were Erik Melén, MD, from the Karolinksa Institute and Sachs’ Children and Youth Hospital in Stockholm Sweden, and Gerard H. Koppelman, MD, from the University of Groningen and Beatrix Children’s Hospital in The Netherlands.

Highlighting the Understudied Phenotype

As Drs. Mishra, Celedón, and colleagues discuss, asthma in school-aged children is far from a monolithic condition; it is a disease comprised of a variety of phenotypes and endotypes, each with its own set of characteristics, disease trajectory, causative factors, and treatment approaches.

One of these asthma subtypes, "Type 2 or T2-low" asthma, comprises two endotypes (“T17-high asthma” and “T2-low/T17-low asthma”) and has historically been “unacknowledged and understudied.” The thrust of the commentary advocates for a heightened research focus on this form of asthma given its often difficult to treat nature.

“T2-low asthma is likely to be more frequent than previously thought in school-aged children. Recognizing this is important, since T2-low asthma often has more severe trajectories in patients,” says Dr. Celedón.

What is T2-Low Asthma and Why It Matters?

T2-low asthma in children is typically characterized by lower levels of Type 2 inflammation, which is commonly associated with eosinophilic and allergic inflammatory pathways. Unlike T2-high asthma, which is often linked to reactions to things like pollen and can respond well to corticosteroid therapy, T2-low asthma does not show elevated levels of markers of T2-high inflammation and is challenging to treat because standard of care therapies like corticosteroids are often ineffective or provide suboptimal control of symptoms or disease exacerbations.

“It’s fundamentally a different disease,” says Dr. Celedón. “We can’t treat T2-low asthma the same as other types of asthma, nor can we or should we study the disease at the pathophysiological level in the same ways as we do T2-high asthma.”

The causes of T2-low asthma are likely multifaceted, involving a mix of genetic, environmental, and immunological factors. Due to its unique characteristics, T2-low asthma should require alternative management strategies.

Call to Action for Enhanced Research

The commentary by Drs. Mishra, Celedón and colleagues offers a strong call to action for the asthma research and clinical care communities. As they discuss, more concerted efforts are essential for advancing the understanding of T2-low asthma, finding useful biomarkers of the disease, and developing novel therapeutics that can work to reduce disease symptoms and severity.

Read the Commentary

Mishra PE, Melén E, Koppelman GH, Celedón JC. T2-Low Asthma in School-Aged Children: Unacknowledged and Understudied. Lancet Respir Med. 2023 Dec; 11(12): 1044-1045.