Journal of Allergy and Clinical Immunology-In Practice最新文献

Eosinophilic lung diseases (ELDs) represent a heterogeneous group of airway and parenchymal disorders unified by eosinophilic inflammation but distinguished by diverse clinical features, mechanisms of persistence, and variable therapeutic responses. Traditional diagnostic tools, including blood eosinophil counts, bronchoalveolar lavage, sputum cytology, and exhaled nitric oxide, predict the eosinophilic/T2 burden of the disease but often fail to distinguish IL-5-dependent from IL-5-independent pathways, overlook compartment-specific inflammation, and inadequately predict or monitor response to targeted biologics. The inconsistent efficacy of IL-5/IL-5R-directed monoclonal antibodies despite normalization of blood eosinophils across the ELD spectrum (robust clinical response in eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome, partial in asthma and largely absent in chronic obstructive pulmonary disease) underscores the limitations of current biomarkers and the need for refined precision endotyping. To address these gaps, emerging biomarker platforms move beyond eosinophil enumeration to define upstream drivers, activation states, tissue localization, and immune pathways sustaining persistent eosinophilia. These advances include noninvasive tools such as lateral-flow devices for assaying eosinophil peroxidase (eosinophil activity biomarker), breathomics and volatile organic compound profiling, cytokine-level inflammatory mapping, and composite biomarker models integrating airway, blood, and molecular signatures. In parallel, functional imaging modalities, including hyperpolarized gas magnetic resonance imaging, phase-resolved functional lung magnetic resonance imaging, and quantitative computed tomography, provide noninvasive, high-resolution visualization of regional ventilation, perfusion, and inflammation. This enables clinicians to look into the lungs and offer powerful stand-alone or complementary biomarker capability. Collectively, these innovations mark a shift toward mechanistically-informed, tissue-specific, multimodal biomarker strategies that refine diagnosis, improve therapeutic selection, and enhance monitoring across the ELD spectrum, advancing the promise of precision medicine.

Oral immunotherapy (OIT) is effective for inducing desensitization to food allergens and continues to be investigated in many clinical trials, either alone or in combination with adjunct therapies. However, adverse events (AEs) such as gastrointestinal (GI) symptoms are common during OIT. These symptoms can pose a considerable management challenge for investigators adhering to clinical trial protocols with strict study windows where extended dosing interruptions are not feasible. GI symptom management practices in the previous clinical trials have usually been left to the discretion of each study site, resulting in a wide heterogeneity of management practices that could lead to substantial variability between sites. In the Omalizumab as a Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy (OIT) in Food Allergic Children and Adults (OUtMATCH) randomized controlled clinical trial (NCT03881696) assessing omalizumab and multiallergen OIT, a critical need for a unified approach for managing GI AEs was identified. To address this need, a subcommittee comprising investigators, both allergists and gastroenterologists, within and outside of the Consortium of Food Allergy Research, developed a working definition for persistent GI AEs during OIT along with a management plan to be used within the ongoing OUtMATCH trial. We present here the definition and management plan, along with illustrative case-based scenarios encountered during the trial. Implementing a management plan for GI AEs during OIT clinical trials has the potential to create standardization, enhance symptom monitoring, improve outcome classification, allow for stratification of AEs related to GI symptoms, and improve safety outcomes for study participants.

Background: Early recognition of inborn errors of immunity (IEI), formerly primary immunodeficiencies, is crucial, yet the diagnostic accuracy of widely promoted clinical "warning signs" in children is uncertain.

Objective: To assess the diagnostic accuracy of clinical warning signs and established criteria for identifying paediatric IEI.

Methods: We searched MEDLINE and EMBASE (inception-May 2024) for studies reporting sensitivity and specificity of individual or combined warning signs in children (0-18 years) with suspected IEI. The reference standard was physician-confirmed IEI. Data were synthesised descriptively and, where appropriate, using bivariate random-effects models. Risk of bias was assessed with QUADAS-2.

Results: Twelve studies (∼7,000 participants, eight countries) met inclusion criteria. Diagnostic performance was highly heterogeneous, and pooled estimates are exploratory. Overall, most individual warning signs showed high specificity but low sensitivity; family history of IEI and signs such as persistent thrush, deep-seated abscesses and failure to thrive were generally highly specific but insensitive. Infection-based signs such as recurrent pneumonia or need for intravenous antibiotics provided a more balanced but still imperfect profile. Combinations of signs, including the Jeffrey Modell Foundation (JMF) threshold of ≥2 warning signs, improved sensitivity in some settings but with variable specificity, and up to one third of children with IEI did not meet any JMF warning-sign criteria.

Conclusions: Traditional warning signs have good rule-in but poor rule-out value for paediatric IEI. Reliance on these signs alone risks delayed or missed diagnoses, particularly for non-infectious IEI phenotypes. Context-specific criteria and decision-support tools are needed to better capture the breadth of IEI presentations and support timely referral.