RESUMO
Background: The use of biologic agents for severe asthma has transformed management, decreasing asthma exacerbations, improving lung function, reducing corticosteroid use, and decreasing hospitalizations. However, numerous financial and logistic barriers have complicated the implementation of biologic agents, including long wait times to see specialists and insurance coverage. Observations: A retrospective chart review was performed for 15 patients enrolled in this severe allergy clinic at the Washington DC Veterans Affairs Medical Center over 30 months. Outcomes examined included emergency department visits, hospitalizations, intensive care unit (ICU) stays, forced expiratory volume (FEV1), and steroid use. The average use of steroids decreased from 4.2 to 0.6 tapers per year following the initiation of biologics. There was an average 10% improvement in FEV1 after starting a biologic. Thirteen percent of patients (n = 2) had an emergency department visit for an asthma exacerbation since starting a biologic agent, 0.6% of patients (n = 1) had a hospital admission for an asthma exacerbation, and no patients had an ICU stay. Conclusions: Biologic agents have significantly improved outcomes for patients with severe asthma. The model of a combined allergy/pulmonology clinic can be particularly efficacious in the treatment of severe asthma, as it reduces the need for multiple appointments with different specialties, reduces wait time before starting a biologic agent, and offers the perspective of 2 specialists.
RESUMO
Repetitive exposure of Rag1-/- mice to the Alternaria allergen extract generated a form of memory that elicited an asthma-like response upon a subthreshold recall challenge 3-15 wk later. This memory was associated with lung ICOS+ST2+ ILC2s. Genetic, pharmacologic, and antibody-mediated inhibition and adoptive transfer established an essential role for ILC2s in memory-driven asthma. ATAC-seq demonstrated a distinct epigenetic landscape of memory ILC2s and identified Bach2 and AP1 (JunD and Fosl2) motifs as major drivers of altered gene accessibility. scRNA-seq, gene knockout, and signaling studies suggest that repetitive allergenic stress induces a gene repression program involving Nr4a2, Zeb1, Bach2, and JunD and a preparedness program involving Fhl2, FosB, Stat6, Srebf2, and MPP7 in memory ILC2s. A mutually regulated balance between these two programs establishes and maintains memory. The preparedness program (e.g., Fhl2) can be activated with a subthreshold cognate stimulation, which down-regulates repressors and activates effector pathways to elicit the memory-driven phenotype.