Type 1 Immune Responses Related to Viral Infection Influence Corticosteroid Response in Asthma

Area of Science:

• Immunology
• Pulmonology
• Genetics

Background:

• Corticosteroid-responsive type 2 (T2) inflammation defines the T2-high asthma endotype.
• Type 1 (T1) inflammation, potentially linked to viral infections, may also affect corticosteroid response in asthma.

Purpose of the Study:

• To determine the prevalence and variability of T1-high, T2-high, and T1/T2-high asthma endotypes.
• To investigate if virally influenced T1-high asthma impacts corticosteroid responsiveness.

Main Methods:

• Analysis of sputum gene expression and viral metagenomics in Severe Asthma Research Program-3 (SARP-3) participants.
• Profiling patients based on T1 and T2 gene network expression to assess endotype-specific corticosteroid response and viral association.

Main Results:

• 22% of asthma patients exhibited high T1 gene expression, 35% high T2, and 8.5% both.
• T2-high asthma showed worse outcomes than T1-high; T1-high/T2-high patients had the most severe disease.
• Corticosteroids suppressed T2 but not T1 gene expression, with FEV1 improvement only in T1-low/T2-high patients.
• Viral detection in 24% of samples correlated with a 14-fold increased risk of T1-high disease.

Conclusions:

• Airway T1 immune responses are prevalent in asthma and largely resistant to corticosteroids.
• T1-high asthma is associated with subclinical viral infections.
• Asthma endotyping based on T1/T2 inflammation is crucial for understanding corticosteroid response and disease severity.