At CHEST’s Sunday afternoon session, Advances in Non-T2 Asthma, experts pondered the semi-vague definition of non-T2 asthma, its current treatments, and potential targets for new therapies. 

According to research published in 2024 in the European Respiratory Journal, heterogeneous phenotypes of asthma include type 2 (T2) and non-T2 asthma. In fact, 30-50% of patients present with non-allergic, non-eosinophilic, non-T2 asthma.

Advances in non-type 2 severe asthma: from molecular insights to novel treatment strategies. European Respiratory Journal

“[This is] an incredibly important topic in the study of chronic respiratory disease,” Sunita Sharma, MD, said during the session. She also shared research on the epidemiology of non-T2 Asthma, clarifying the distinctions between T2 inflammation and non-T2 neutrophilic inflammation.

Some distinguishing features? T2 patients are generally corticosteroid sensitive, while non-T2 are corticosteroid insensitive. In non-T2, cytokines IL-6, 8, 17, and 1β may play a role. Other pathways may also contribute to non-T2, she said, including neutrophil extracellular traps, airway dysbiosis, nitric oxide signaling, and more.

Biomarkers associated with non-T2 include: 

• Blood eosinophils (>150-300 cells μl), IgE (>100 IU/ml) Specific IgE (present with exposure to antigen causing symptoms) Fraction of exhaled nitric oxide, or FeNO (>35 ppb in 5-12 years and 50 ppb in people over 12).

• In low-T2 asthma, specific IgE is undetectable, and FeNO is <20 and <25, respectively.

To dive into the topic further, Adrish then introduced the room to a “patient” called Jane: She was 49, with a history of asthma. She smokes, has a BMI of 34, and has other health conditions.

“Most of the clinicians in this room have probably seen some version of Jane,” he said. The room nodded in agreement. Participants were then asked whether or not Jane has non-T2 asthma—and the overall answer was, “maybe.” While biomarkers like IgE and FeNO, and specific IgE can help determine a patient’s status, it that’s not a catch-all. What everyone did agree on is the fact that “Jane” should quit smoking, lose weight, and seek pulmonary rehabilitation—something the research supports for many patients. 

Treating non-T2 asthma: Now and tomorrow

Dr. Akuthota discussed some of the effective and not-so-effective treatments for non-T2. Inhaled corticosteroids are less effective in non-T2, while long-acting muscarinic antagonists (LAMAs) and azithromycin are more effective, he said. Also available for non-T2 patients? Tezepelumab, a biologic for patients with poorly controlled moderate to severe asthma regardless of whether they are T2 or non-T2.

“There’s room for a lot of advances to be made,” Dr. Akuthota added. “One place some thought is put into is the JAK inhibitor. We see this in rheumatological disease but it is a potential players in asthma as well,” he says. Other explorations include tyrosine kinase inhibitors (for low-T2), among others. 

“Don't lose hope. There are things we may see in the future,” Dr. Akuthoka said, leaving the session on a hopeful note.