Type-2-low severe asthma endotypes for new treatments: the new asthma frontier.
Level 5 - mechanism / opinion, no new human data
Narrative review of molecular endotypes and potential therapeutic targets without new primary data or systematic review methodology.
PubMed 37185823 · doi:10.1097/ACI.0000000000000899
What was done
This is a narrative review examining molecular endotyping and therapeutic avenues for Type-2 (T2)-low severe asthma (clinically identified by low blood eosinophil counts). The authors review findings from transcriptomic and proteomic profiling of sputum samples from the U-BIOPRED cohort and evaluate why prior targeted therapies for non-eosinophilic asthma failed.
What was found
The abstract reports no numerical values or effect estimates. It qualitatively describes specific molecular clusters in T2-low asthma: a neutrophilic-predominant cluster marked by inflammasome activation, interferon, and tumour necrosis factor expression; a paucigranulocytic cluster linked to oxidative phosphorylation and senescence pathways; and phenotypes driven by IL-6 trans-signalling, IL-17, and IL-22 pathways linked to neutrophilic or mixed granulocytic inflammation. It notes that prior trials of antineutrophilic therapies failed because enrollment was not guided by these molecular phenotypes.
Why it matters
Patients with T2-low severe asthma lack effective targeted treatments. Identifying precise molecular endotypes provides a rationale for testing existing biologic agents approved for other autoimmune disorders in enriched patient subsets.
Limits
The abstract provides no quantitative data, sample sizes, or effect sizes. As a narrative review, it presents mechanistic and biomarker associations primarily derived from a single cohort (U-BIOPRED), which require prospective validation in independent cohorts before clinical adoption.
Cited by
- supports There are approximately seven or eight distinct subtypes of asthma, with variations including eosinophil-predominant or neutrophil-predominant profiles.