This Week in Allergy & Immunology — Sep 6, 2026

Welcome to This Week in Allergy & Immunology. This week we're covering 10 notable papers spanning biologic therapy for type 2 airway disease, biomarkers that predict who responds to treatment, and the practical business of drug and food challenge testing in the allergy clinic. Let's dive in.

We'll start with biologics and type 2 airway inflammation, where the most clinically consequential paper this week comes from the Journal of Allergy and Clinical Immunology. Bourdin and colleagues report a double-blind phase 2 trial of dupilumab in allergic bronchopulmonary aspergillosis, a condition for which we currently have no approved targeted therapy [1]. Sixty-two patients aged twelve and over with asthma meeting clinical criteria for ABPA were randomised to dupilumab or placebo for 24 to 52 weeks, and about 37 percent of participants were on chronic systemic corticosteroids at entry. At 24 weeks, pre-bronchodilator FEV1 improved by roughly 200 millilitres more with dupilumab than with placebo, and that difference was statistically significant. Severe respiratory exacerbations fell by about 55 percent, though I want to be precise here: that exacerbation reduction did not reach statistical significance, and the authors report it as a nominal comparison. The finding most likely to change your clinic day is the steroid result. Among dupilumab recipients who needed systemic corticosteroids at baseline, just over seventy percent were off them by week 24, compared with roughly one in seven on placebo. Safety was consistent with what we already know about dupilumab. This is a phase 2 signal, not a licensing dataset, but for a disease we have historically managed with prolonged prednisone and antifungals, it is a meaningful one.

Staying with type 2 disease, the Journal of Allergy and Clinical Immunology also publishes a review by Corren and colleagues on what a decade of thymic stromal lymphopoietin inhibition has taught us [9]. TSLP sits upstream at the epithelial barrier, driving both type 2 and non-type 2 inflammation, and the review walks through the trial evidence across asthma, chronic rhinosinusitis with nasal polyps, chronic obstructive pulmonary disease, allergic rhinitis, atopic dermatitis and chronic spontaneous urticaria. Tezepelumab remains the only approved anti-TSLP agent, but the authors list roughly a dozen further TSLP-targeting molecules in clinical development — which tells you the competitive landscape in upstream epithelial cytokine blockade is about to get considerably more crowded. Alongside that, Annals of Allergy, Asthma and Immunology reports a pooled subgroup analysis of the ReOpen1 and ReOpen2 trials of the exhalation delivery system with fluticasone in chronic rhinosinusitis [4]. Across 547 patients, symptom scores, SNOT-22 and global impression of change all improved with active treatment compared with the placebo delivery system, and critically the benefit held regardless of whether patients had asthma, environmental allergy, or blood eosinophils above or below 300 cells per microlitre. There was no meaningful treatment-by-subgroup interaction. The practical message is that you do not need to endotype a chronic rhinosinusitis patient before offering this topical option — though the authors themselves note the limitations of a subgroup analysis.

That brings us to the theme of biomarkers that stratify who will respond, where Annals of Allergy, Asthma and Immunology publishes a study that could reshape how we think about chronic spontaneous urticaria. Marcelino and colleagues, in the multicentre INCA study across five Portuguese centres, measured complement fractions in 159 patients with chronic spontaneous urticaria [2]. Serum C5 showed a clean bimodal distribution, splitting the cohort into two biologically distinct groups. Patients with low or normal C5 had higher total IgE, fewer autoantibodies, limited complement activation — and an 89 percent response rate to standard-dose omalizumab. Patients with high C5 had elevated C3 and C5a, more autoimmune thyroid disease, more IgG and IgE autoantibodies, and only a 36 percent response rate. That is a striking separation, and it maps onto the autoallergic versus autoimmune endotypes we've been describing conceptually for years. This is cross-sectional data and needs prospective validation before you order C5 on every urticaria patient, but if it holds, a simple serum complement level could tell you in advance which patients are likely to need dose escalation or an alternative agent rather than a long trial of standard-dose omalizumab.

In Allergy, Khaitov and colleagues report early clinical data on a recombinant birch pollen vaccine, GNR-127, built from Bet v 1-derived peptides fused to a hepatitis B PreS carrier protein [7]. After an open-label dose-finding stage, 132 patients were randomised to placebo or one of two doses, given as up to five monthly pre-seasonal subcutaneous injections. The combined symptom-medication score fell in a dose-dependent way, with about a 24 percent reduction over placebo at the 80 microgram dose, and that was the only dose reaching statistical significance. It came with a robust immunological signature: a roughly twenty-fold rise in Bet v 1-specific IgG, blunting of the seasonal IgE boost, and reduced basophil sensitivity. Safety was acceptable. This is a phase 2 result pointing toward a phase 3 trial, but a five-injection pre-seasonal course is an appealing prospect compared with three years of conventional immunotherapy.

Our third theme is the practical work of challenge testing, and here three papers converge on the same question: how do we do this more safely and more efficiently? From International Archives of Allergy and Immunology, Rojas Perez-Ezquerra and colleagues propose PENFAST-A, a modification of the PENFAST penicillin allergy decision rule adapted for allergist-led settings [3]. In a retrospective tertiary-centre cohort, the modified score raised sensitivity from about 82 percent to about 95 percent and pushed the negative predictive value above 97 percent, at the cost of specificity dropping to around 44 percent. The headline safety point is that no patient scoring below 2 on PENFAST-A had a confirmed beta-lactam allergy. In a specialist clinic, where the case mix is enriched for unusual low-risk phenotypes, that trade — catching more true allergies at the price of sending more patients to formal testing — is probably the right one.

The same journal publishes a real-world cohort from Ramirez Villamizar and colleagues applying the new EAACI/ENDA 2024 risk stratification retrospectively to 161 patients who all underwent an identical placebo-free, two-step, equal-dose drug provocation protocol [5]. Overall about eleven percent of challenges were positive, but positivity tracked the risk categories sharply: around five to nine percent in the low and intermediate groups, versus about 62 percent in the high-risk group. Most striking, among patients reclassified as high risk purely because of isolated early urticaria or angioedema, seven of eight had a positive challenge. Two patients — a bit over one percent — developed anaphylaxis, both after the first dose, which is an argument for keeping that first step small and supervised. And from the same journal, Yoshida and colleagues examined wheat oral food challenges in 337 Japanese children with omega-5 gliadin-specific IgE below 3.5 [6]. Just under a quarter of challenges were positive, and interestingly that rate was essentially identical whether wheat-specific IgE was high or low — suggesting omega-5 gliadin is doing the discriminating work. Anaphylaxis occurred in six cases, about two percent, none requiring intramuscular adrenaline. At low doses, under about 52 milligrams of wheat protein, more than nine in ten children tolerated the challenge, supporting a low starting dose as a safety measure.

Two mechanistic and preventive papers round out the week. In the Journal of Allergy and Clinical Immunology, Zhang and colleagues profiled oral short-chain fatty acids, the oral microbiome, and blood transcriptomes in 56 children randomised to peanut oral immunotherapy or avoidance [8]. Every child in the OIT arm achieved desensitisation, against fewer than one in five in the avoidance arm. Oral propionate rose with immunotherapy but not avoidance, stayed elevated in those with sustained unresponsiveness, correlated with propionate-producing oral bacteria such as Prevotella and Veillonella, and correlated inversely with blood expression of IL-4 and IL-13 signalling. It is hypothesis-generating, but it proposes a plausible bridge between the mouth and systemic immune regulation. And in Allergy, Smeekens and colleagues review the external exposome in food allergy [10], covering allergen exposure in household dust, farm and microbial exposures, air pollution, synthetic chemicals and ultra-processed foods — a useful framing for the prevention conversations we increasingly have with new parents.

If you only have time for one paper this week, make it the dupilumab trial in allergic bronchopulmonary aspergillosis [1]. It is the first randomised evidence for a targeted biologic in a disease with no approved therapy, and the corticosteroid-sparing result addresses the single biggest source of harm in these patients.

Here are the key takeaways from this week in Allergy and Immunology. First, dupilumab improved lung function and got most steroid-dependent ABPA patients off systemic corticosteroids in a phase 2 trial, though the exacerbation reduction was not statistically significant. Second, serum C5 may split chronic spontaneous urticaria into a group that responds well to standard-dose omalizumab and one that largely does not — watch for prospective validation. Third, the exhalation delivery system with fluticasone worked in chronic rhinosinusitis regardless of asthma, allergy or eosinophil status, so endotyping is not a prerequisite. Fourth, in drug provocation testing, isolated early urticaria or angioedema is a genuinely high-risk history, and anaphylaxis when it occurs tends to happen on the first dose — start low. And fifth, in children with low omega-5 gliadin-specific IgE, wheat challenges are reasonably safe, and a low starting dose makes them safer still.

That's your roundup for This Week in Allergy & Immunology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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