American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2025
Type 1 Immune Responses Related to Viral Infection Influence Corticosteroid Response in Asthma.
Rationale: Corticosteroid-responsive type 2 (T2) inflammation underlies the T2-high asthma endotype. However, we hypothesized that type 1 (T1) inflammation, possibly related to viral infection, may also influence corticosteroid response. Objectives: To determine the frequency and within-patient variability of T1-high, T2-high, and T1/T2-high asthma endotypes and whether virally influenced T1-high disease influences corticosteroid response in asthma. ⋯ Corticosteroid treatment strongly suppressed T2 but poorly suppressed T1 gene expression, and corticosteroid-associated improvements in FEV1 occurred only in patients with T1-low/T2-high disease and not in patients with T1-high/T2-high disease. Viral metagenomic analyses uncovered that 24% of asthma sputum samples tested positive for a respiratory virus, and high viral carriage was associated with 14-fold increased risk of T1-high disease. Conclusions: Airway T1 immune responses are relatively common in asthma, are largely corticosteroid resistant, and are associated with subclinical viral infection.