Allergy & Immunology

Sphingolipid-to-steroid ratios provide a high-performance 5-year asthma exacerbation risk biomarker

Across three asthma cohorts, sequential metabolomics linked specific sphingolipid-to-steroid serum ratios to future 5-year exacerbation risk. A predictive model using 21 such ratios achieved AUC 0.90 in discovery and 0.89 in replication, outperforming current clinical measures. Associations were highly significant in discovery and replication datasets, suggesting a robust and reproducible signal. These data support translation of targeted sphingolipid-steroid assays into practical tools for longer-term exacerbation risk stratification. 1

Biologics remain effective in severe asthma patients who would be ineligible for pivotal RCTs

This UK registry study analyzed 1421 adults with severe asthma on biologics for at least one year. Composite response required at least 50% reduction in exacerbations or maintenance oral corticosteroid dose. Noninferiority of response was shown for all trial eligibility themes except medication adherence. Patients failing adherence criteria had markedly lower odds of response, whereas low baseline symptom burden predicted higher odds. Findings support biologic use in a broad severe asthma population while underscoring the importance of optimizing adherence. 2

Early-life loss of SCFA-producing microbiota epigenetically programs HSPCs toward atopy

Neonatal antibiotics that deplete short-chain fatty acid–producing gut bacteria reprogrammed hematopoietic stem and progenitor cells in mice. Bone marrow from exposed donors induced elevated serum IgE, increased IgE-bound basophils, and worsened papain-induced allergic lung inflammation in recipients. SCFA-producer depletion impaired recovery from chemotherapy-induced myelosuppression and increased long-term HSPC DNA damage in an antibiotic-specific manner. H3K27 ChIP-seq demonstrated altered histone acetylation in HSPCs, supporting an SCFA-mediated epigenetic mechanism. These findings causally link early-life microbiota composition to durable allergic susceptibility and hematopoietic resilience. 3

A parallel “two-tailed” workup streamlines real-world hypereosinophilic syndrome diagnosis

In 247 referred patients with hypereosinophilia, a two-tailed strategy simultaneously assessed etiology and organ damage. One hundred sixty-eight were excluded due to secondary causes or lack of sustained hypereosinophilia, leaving 79 with hypereosinophilic syndrome. Reactive, overlap, lymphocytic, myeloid, and idiopathic subtypes were all identified, with most patients having at least two organs involved. Lung, skin, bowel, peripheral nerves, and heart were commonly affected, and diagnosis was typically achieved in about four months. No deaths occurred, suggesting that structured parallel evaluation may reduce misclassification, shorten delay, and facilitate timely targeted therapy. 4