Allergy & Immunology

Blood eosinophils and FeNO show diagnosis- and subtype-specific links to exacerbations in asthma and COPD

In the multicountry NOVELTY cohort, higher baseline blood eosinophils were associated with increased all-exacerbation risk in physician-diagnosed asthma and trended similarly in COPD. In asthma, combined assessment of higher eosinophils and FeNO further increased exacerbation risk, particularly for oral corticosteroid–treated episodes. In COPD, higher eosinophils and lower FeNO were independently associated with higher exacerbation risk, contrasting with patterns seen in asthma. Higher FeNO predicted more oral corticosteroid–treated exacerbations in asthma and asthma+COPD but fewer total exacerbations in COPD. Interpretation is limited by physician-assigned diagnoses, background inhaled corticosteroids, and recall of prior exacerbations. 1

Gut dysbiosis–TMAO axis drives Th2 skewing and worsens atopic dermatitis

In mice, intestinal epithelial TLR4 deficiency reshaped the microbiome, reduced Akkermansia, enriched CutC+ bacteria, and exacerbated experimental atopic dermatitis. This dysbiosis increased choline-to-trimethylamine conversion and circulating TMAO, which promoted Th2 differentiation via PPP5–PPARγ signaling in CD4+ T cells. CD4+ T cell–specific PPARγ deletion abolished TMAO-driven skin pathology, functionally linking this metabolite pathway to disease expression. Patients with atopic dermatitis had higher plasma TMAO correlating with disease severity and IgE, and higher dietary choline intake associated with increased AD risk in UK Biobank. These data support targeting diet–microbiome–metabolite axes as a potential adjunctive approach in atopic dermatitis, pending interventional confirmation. 2

PD-1 agonist JNJ-3 depletes PD-1high T cells but lacks clear efficacy in moderate–severe atopic dermatitis

In this phase 2a trial, adults with moderate–severe atopic dermatitis were randomized 2:1 to subcutaneous JNJ-3 or placebo for 12 weeks. EASI-75 responses and percentage EASI improvement were numerically higher with JNJ-3 but did not reach statistical significance versus placebo. Similar modest numerical benefits were seen for EASI-50 and SCORAD, indicating limited clinical impact as monotherapy. JNJ-3 induced rapid, sustained, reversible depletion of PD-1–expressing T cells, particularly PD-1high CD4+ cells, confirming pharmacodynamic engagement. Adverse event rates were comparable between groups, suggesting an acceptable safety profile despite underwhelming efficacy. 4