This week in Allergy & Immunology

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Welcome to This Week in Allergy & Immunology. This week we're covering 10 notable papers spanning airway disease from asthma to nasal polyps, early-life atopy and eosinophilic disease, and immunodeficiency and immunogenetics. Let's dive in.

We start with asthma and its relatives, where several papers ask who is being left behind by standard care. In the Journal of Allergy and Clinical Immunology, Bari and colleagues ran a post-hoc analysis of the RECONSTRUCT study. They took corticosteroid-free adults with asthma and hyperresponsiveness to mannitol and gave them six weeks of high-dose inhaled budesonide, 1600 micrograms daily, with bronchoscopy before and after [1]. Indirect hyperresponsiveness usually melts away with inhaled steroids, yet about a quarter of patients, 11 of 46, still had it at six weeks. Those incomplete responders started with more severe hyperresponsiveness, higher exhaled nitric oxide, more blood and sputum eosinophils, and a denser population of chymase-positive airway mast cells. After treatment they still carried more eosinophils. The authors read this as a signal of type 2 inflammation that inhaled steroids alone do not fully suppress. The sample is small and the analysis exploratory, so it points toward a candidate subgroup for closer follow-up rather than a validated test.

The randomized evidence this week comes from Agarwal and colleagues in The Journal of Allergy and Clinical Immunology: In Practice. Their single-centre, open-label trial randomized 178 adults with newly diagnosed allergic bronchopulmonary aspergillosis to 16 weeks of deflazacort or prednisolone [2]. On the primary outcome deflazacort worked as hoped. Weight gain at eight weeks was about two percentage points lower, roughly three percent versus five percent. Response at eight weeks was similar in both arms, over ninety-five percent. The trade-off came later. The fall in total IgE was smaller with deflazacort, and exacerbations within one year more than doubled, about eighteen percent versus eight percent. A composite of early failure or first exacerbation leaned against deflazacort but did not reach statistical significance. The authors call for dose-ranging studies rather than endorsing a switch. As it stands, the trial suggests that a metabolic advantage may cost some disease control.

Two papers widen the lens to the patient's circumstances. Schatz and colleagues, also in In Practice, surveyed 3,787 adults whose asthma looked mild by healthcare use [3]. More than half of participants reported at least one health-related social need, such as food or housing insecurity. About a quarter of participants screened positive for depression or anxiety. Depression raised the risk of very poorly controlled asthma by roughly half. One social need was linked to very poor control, and two or more were linked to emergency or urgent care visits. Anxiety on its own was not independently associated with either outcome. The worst outcomes clustered in people with both social needs and mood symptoms. This is cross-sectional and self-reported, so it shows association rather than cause. Still, it suggests that low utilization does not mean low risk. A systematic review in Current Allergy and Asthma Reports by Chen and colleagues makes a similar point about older adults [4]. Asthma prevalence in this age group is rising, but the disease remains underdiagnosed and undertreated. The review cites atypical presentation, overlap with COPD, comorbidity, poor inhaler technique and uneven access to biologics, and calls for age-adapted diagnostic protocols.

The upper airway gets a pair of complementary reviews on when and how to escalate chronic rhinosinusitis, both in The Journal of Allergy and Clinical Immunology: In Practice. Desrosiers and colleagues argue that sinus surgery and biologics are mechanistically distinct rather than interchangeable [5]. Surgery is a local intervention that removes inflammatory burden and allows the epithelium to recover. Biologics suppress type 2 inflammation systemically. They conclude that current evidence supports surgery as the cost-effective first step after intranasal steroids fail, with biologics for refractory disease or selected high-risk phenotypes. Pirola and Hopkins look at what should come before either option [6]. Intranasal steroids and saline remain the foundation of treatment. Repeated courses of systemic steroids carry serious cumulative harm. They find that the evidence for long-term macrolides is inconsistent, especially in type 2 disease, and that it should not be a universal hurdle before escalation. In their view, antihistamines and immunotherapy belong only where allergy is clinically relevant, not where there is sensitization alone. Both reviews reflect expert synthesis rather than new trial data. The surgery-first framing, in particular, may be debated by clinicians who favour earlier biologics in heavily comorbid patients.

Turning to children, two papers address early-life atopy and eosinophilic disease. In Pediatric Allergy and Immunology, Cremin and colleagues report the five-year blinded follow-up of the STOP-AD trial [7]. High-risk newborns were randomized within four days of birth to twice-daily whole-body emollient for eight weeks or to routine skin care. At five years, 177 children were assessed. Atopic dermatitis was present in about twelve percent of the emollient group and twenty-four percent of controls, roughly half the prevalence. Children who did develop eczema had milder disease. The authors are candid about the limits. The primary result only just reached statistical significance, and when missing data were imputed the effect was similar in size but no longer statistically significant. Attrition and a single-centre design leave real uncertainty. Emollient prevention trials have been inconsistent overall, so this result keeps the question open rather than settling it.

In the Journal of Allergy and Clinical Immunology, Kellerman and colleagues examined persistent pain in pediatric eosinophilic esophagitis [8]. Among 1,097 patients at Cincinnati Children's Hospital, they used natural language processing to find the roughly four percent with clinically significant persistent pain. They then compared these children with matched patients who had no pain. Eosinophil counts and dysphagia were similar between the groups, but the children with pain were older at presentation, at about thirteen years versus eight. They also had more comorbidities, more polytherapy and more treatment changes, and their endoscopy burden grew over time. Esophageal biopsies showed lower ALOX15 expression, particularly in children in remission. The authors propose a candidate pain endotype. It comes from retrospective, single-centre data, so it is a hypothesis to test rather than a classification ready for use.

Our final theme is immunodeficiency and immunogenetics. In the Journal of Allergy and Clinical Immunology, Haerynck and colleagues present European Society for Immunodeficiencies consensus vaccination guidelines aligned with the 2024 international classification of inborn errors of immunity [9]. The panel states that non-live vaccines are safe across all of these disorders, although protection varies with the underlying defect. Live attenuated vaccines are contraindicated in many subtypes, but individual assessment may allow exceptions. Influenza and pneumococcal vaccination are strongly recommended. New guidance covers tick-borne encephalitis, SARS-CoV-2, treatment-specific scenarios and travel. This is expert consensus, with agreement defined as at least three quarters of the panel, but its subtype-level detail fills a practical gap. Also in that journal, Boquett and colleagues linked high-resolution HLA typing to self-reported health histories in 70,724 registry donors [10]. They found 48 associations, including fourteen novel ones, many of them involving allergic and infectious conditions that are often missing from health records. The most striking was HLA-DRB1 star 04 colon 01, which was linked to almost four times the odds of a self-reported cefaclor reaction label. Several of the novel associations replicated in the All of Us cohort. Because the reactions are self-reported and unverified, the authors frame this as pharmacogenomic groundwork that needs clinical and functional validation.

If you only have time for one paper this week, make it the deflazacort trial in allergic bronchopulmonary aspergillosis [2]. It is a rare randomized head-to-head steroid comparison in this disease, and it shows that sparing weight may come at the price of more exacerbations. That reopens the question of how to balance steroid toxicity against durable control.

That's your roundup for This Week in Allergy & Immunology. The full transcript and references are available on the episode page. See you next week.

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