Frontiers in allergy最新文献

Consumption of an amino acid-based formula (AAF) with added synbiotics [short-chain oligofructose and long-chain inulin (scFOS/lcFOS, 9:1 ratio) and Bifidobacterium breve M-16V] (AAF-S) beneficially impacts the gut microbiome of infants with cow's milk allergy (CMA). We assessed the effect of consuming AAF with or without synbiotics by children with CMA for 12 months on their fecal (branched) short-chain fatty acids (SCFA/BCFA) concentrations, and on gut barrier and inflammation markers (Netherlands Trial Register NTR3725). Feces and saliva were collected from 161 children (≤13 months) with IgE-mediated CMA at baseline, 6 and 12 months after enrollment, and at 24 and 36 months follow-up. Fecal SCFA and BCFA were analyzed by gas chromatography, and gut barrier and inflammation markers were measured in saliva/feces by ELISA or ImmunoCAP. At 6 months, children receiving AAF-S had significantly lower fecal propionate, valerate and BCFA concentrations compared to children consuming AAF. The percentage of propionate from the total 6 SCFA/BCFA (acetate + butyrate + propionate + valerate + isobutyrate + isovalerate) was significantly lower, while the percentage of acetate from the total 6 SCFA/BCFA was significantly higher in the AAF-S group. There were no significant differences between groups in fecal concentrations of butyrate at 6 months, nor in SCFA or BCFA at baseline and after 12, 24 or 36 months. Intestinal inflammation and barrier markers did not differ between groups. Addition of synbiotics to AAF brings concentrations of key fecal microbial metabolites more in line with patterns observed in healthy breastfed infants. The effects on SCFA and BCFA concentrations were transient and only seen at 6 months.

Asthma is a heterogeneous condition influenced by multiple clinical and biological factors, and obesity has emerged as a major modifier that worsens symptoms and increases the risk of exacerbations. This review aimed to examine the mechanisms by which obesity contributes to reduced responsiveness to corticosteroids, which remain the cornerstone of guideline-based asthma management. We reviewed evidence from clinical and experimental studies describing how adipose tissue dysfunction, chronic low-grade inflammation, oxidative stress, and systemic comorbidities alter glucocorticoid receptor signalling and downstream pathways. Particular attention was given to immune mechanisms such as neutrophilic inflammation and interleukin-17 signalling, as well as metabolic disturbances including hyperleptinaemia and vitamin D deficiency. We also considered the role of lifestyle factors, such as physical inactivity and dietary patterns, in sustaining corticosteroid insensitivity. Based on these insights, we evaluated both established and emerging therapeutic strategies, including weight loss, structured exercise, dietary modification, and drug repurposing with agents such as metformin, low-dose theophylline, and glucagon-like peptide-1 receptor agonists. A comprehensive synthesis of these findings highlights the need for integrated lifestyle and pharmacological interventions, and provides a framework for the development of targeted treatments to improve outcomes in patients with obesity-associated, corticosteroid-insensitive asthma.

Background: Childhood asthma is common and associated with extensive racial, ethnic and socioeconomic healthcare inequities and health disparities. Approximately 50% of children with asthma are insured by Medicaid in the U.S. and states have increasingly implemented Accountable Care Organization (ACO) models in their Medicaid programs, but little is known about the effects of ACOs on pediatric asthma quality of care, utilization, and disparities. Seventeen new ACOs were implemented in Massachusetts in 2018. Delivery System Reform Incentive Payments were provided to ACOs that could be used to improve outcomes for chronic diseases, such as asthma, through quality measures, enhanced care coordination, and community health worker staffing. This qualitative study explored caregiver experiences with pediatric asthma care for their Medicaid-insured child following ACO implementation in Massachusetts.

Methods: Semi-structured virtual interviews were conducted with caregivers of Medicaid-insured children with asthma in Massachusetts between July 1-December 31, 2023. Purposive sampling aimed to include a range of participant and practice characteristics. The overarching theoretical framework was an adaptation of the Framework of Asthma Disparities, and data were analyzed using rapid qualitative analytic methods.

Results: Of the 26 participants, 96% were female; 23% identified as Black and 39% as Hispanic. Key themes included: (1) Perceived lack of changes in asthma care related to Medicaid ACO implementation; (2) Insurance coverage influences on asthma care; (3) Perceptions of asthma management in primary care; (4) Perceptions of asthma specialist care; (5) Influence of health related social needs on pediatric asthma care and outcomes; and (6) Suggestions for improving pediatric asthma care in Medicaid ACOs. Continuity of care, communication, and asthma education were prominent subthemes.

Conclusions: Medicaid ACOs efforts to transform care delivery through increased resources and improved infrastructure for care coordination and other aspects of care may not have had a substantial influence on asthma care for children in early years of implementation, addressing a gap in knowledge about mixed-age ACOs' effects on pediatric populations. Participants' perceptions of the importance of care continuity, specialty access, and education may warrant further exploration in general and in the context of Medicaid ACO effects on asthma care for children at high risk for asthma disparities.

Introduction: Workers in the shellfish industry face increased risks of allergy and asthma due to complex bioaerosol exposures in the workplace. This study aimed to assess whether combined exposure to the main components of these aerosols, specifically allergens and microbial agents, can potentiate inflammatory and allergic responses.

Methods: THP-1 monocytes and advanced human alveolar co-cultures model ALIsens® were exposed to shrimp tropomyosin (0.0049, 1.3 and 2.6 µg/mL), and components from Gram-positive bacteria; lipoteichoic acid (0.25-4 µg/mL), and fungi; zymosan (6.25-100 µg/mL), either alone or in combination. The effects on the gene expression and protein secretion of chemokines and cytokines were assessed by RT-qPCR and ELISA or Luminex.

Results: Combined exposure to tropomyosin and lipoteichoic acid resulted in increased CCL20, CCL2, TNF and IL8 expression and CCL20 and TNF protein secretion in THP-1 cells, when compared to individual exposure. Similarly, tropomyosin combined with zymosan elicited a response pattern, characterised by increased expression and secretion of chemokines and cytokines in most of the tested combinations. Furthermore, the increased secretion of CCL20 and expression of CCL2 following combined exposure to tropomyosin and lipoteichoic acid were confirmed in the alveolar co-culture model, while no effects in combination with zymosan were observed.

Conclusion: These findings suggest that microbial components in shellfish industry bioaerosols may enhance the immunological responses caused by inhaled allergens in an additive manner, highlighting the need to minimise microbial contamination in workplaces where allergen exposure is prevalent.

Background: Chronic Spontaneous Urticaria (CSU) and Atopic Dermatitis (AD) are both immune-mediated inflammatory skin disorders that often co-exist with other atopic conditions such as asthma and allergic rhinitis. Their shared immunopathological pathways raise the question of a possible interrelationship.

Objective: To evaluate the prevalence, clinical features, and immunological profiles of AD in patients with CSU and to explore implications for diagnosis and treatment.

Methods: 425 CSU patients treated in Northern Israel between 2021 and 2024, were retrospectively analyzed. Disease activity was assessed using the Urticaria Activity Score-7 (UAS7) and Investigators' Global Assessment (IGA) for AD. The prevalence of asthma, total serum IgE levels, and therapeutic responses were evaluated.

Results: Among the 425 CSU patients, 42 (10%) were also diagnosed with AD. Co-morbid patients had a higher frequency of asthma (40%) and high total IgE levels (67%) compared to CSU-only patients. A substantial subset of co-morbid cases required biologic treatments with Dupilumab, offering benefit in AD-dominant cases unresponsive to Omalizumab. Severe CSU was more prevalent in the CSU + AD group (though the prevalence was not statistically significant).

Conclusion: CSU and AD frequently co-exist, likely due to overlapping T-cell-mediated immunopathogenic mechanisms. High total IgE and asthma comorbidity may indicate an underlying AD component in CSU patients. Recognition of this overlap is essential for appropriate therapeutic decision-making, including potential escalation to biologic agents targeting T-cell cytokine pathways.

Introduction: Allergic rhinitis (AR) and atopic dermatitis (AD) frequently co-occur, yet their shared molecular mechanisms are poorly understood. We used an integrative bioinformatics approach to identify common diagnostic biomarkers and mechanistic links between them.

Methods: Transcriptomic datasets from AR and AD patients were analyzed to identify overlapping differentially expressed genes (DEGs). Hub genes were subsequently identified using protein-protein interaction (PPI) networks and random forest modeling, followed by functional enrichment and immune infiltration analyses.

Results: Our analysis identified 36 overlapping DEGs between AR and AD. From these, five hub genes-CD274, CYP2E1, FOLH1, SERPINB4, and SPRR1B-were revealed, all of which demonstrated strong diagnostic value in both diseases. Functional analysis indicated their involvement in epithelial barrier regulation, immune cell signaling, and oxidative stress pathways. Immune infiltration profiling showed a significant association between these genes and dendritic cells, T cells, and natural killer cells in both AR and AD cohorts.

Conclusion: AR and AD share a common molecular landscape, and the five hub genes identified here represent robust biomarkers for diagnosis and potential therapeutic targets for these interconnected diseases.

Heiner syndrome (HS), although rare in pediatric practice, can cause cough, wheezing, and only in rare cases hemoptysis. HS should be considered in any child presenting these respiratory symptoms and radiological evidence of alveolar infiltrates, especially when accompanied by signs of food allergy-most notably cow's milk protein allergy, although other foods may also be involved. The use of probiotics should be evaluated with caution in these children. We report a case of a 1-year and 6-month-old female patient who presented at the Pneumology Clinic with a 1-day history of blood-tinged sputum. Although she had a known history of cow's milk protein allergy and well-controlled asthma, the occurrence of hemoptysis, even in small quantities, raised concerns for the family. A second episode of hemoptysis appeared when she consumed egg and probiotics. After correlating the patient's medical history with clinical, laboratory, and imaging findings, a diagnosis of HS was established. The patient received emergency treatment followed by bronchodilators, corticosteroid therapy, and a restricted diet for cow's milk protein and egg. The patient's condition improved immediately after treatment and remained stable at the 5-month follow-up. The differential diagnosis with idiopathic pulmonary hemosiderosis must not be overlooked, due to its more severe clinical course and higher risk of complications.

Background: Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine implicated in the pathogenesis of asthma. However, its expression across different biological specimens and its clinical correlates remain unclear. The objective of this study was to summarize available data on TSLP concentrations in blood and airway specimens in asthmatic patients.

Methods: Studies reporting TSLP concentrations in blood and/or airway specimens [e.g., bronchial biopsy, bronchoalveolar lavage fluid (BALf), induced sputum, exhaled breath condensate (EBC), and nasal specimens] of asthmatic patients compared with healthy controls were eligible. PubMed, Web of Science, Embase, and Cochrane Library were searched from inception to October 2024. A total of 40 studies were included for qualitative synthesis, and 5 were eligible for meta-analysis. Differences in TSLP levels of asthmatic patients and controls were summarized by standardized mean differences (SMD) using a random effects model.

Results: Based on meta-analysis, blood TSLP concentration was significantly higher in patients with asthma than in controls (SMD = 3.66, 95% CI 1.63-5.69, I ² = 98.26%). The sensitivity analysis showed that no individual study influenced the pooled effect estimate. Based on a systematic review, all studies analyzing bronchial biopsies and BALf reported significantly higher TSLP concentration in asthmatics compared with controls, whereas results in induced sputum, EBC, and nasal specimens were variable.

Conclusions: Most studies reported higher blood TSLP concentration in asthma patients compared with healthy controls, while results in airway specimens were diverse. Higher concentration of TSLP in asthmatic patients might be a useful disease-related marker.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024537964, PROSPERO CRD42024537964.

Introduction: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated form of food allergy characterized by gastrointestinal manifestations following ingestion of the offending food. Most cases are identified during the first year of life, most frequently triggered by cow's milk or soy; however, alternative clinical phenotypes beyond this classic presentation have also been reported. In this case, we report a patient who developed acute FPIES to cow's milk ingestion following a COVID-19 infection, despite previous tolerance to cow's milk. This case raises the hypothesis that viral infections such as COVID-19 may act as cofactors or unmasking events in the development of FPIES.

Case presentation: We report a 10-month-old boy who experienced recurrent episodes of profuse vomiting, followed by persistent diarrhea, beginning at 25 days of age-just a few days after a COVID-19 viral illness-with subsequent resolution upon transition to an amino acid-based formula. An oral food challenge (OFC) with cow's milk triggered repetitive emesis within 2 h of ingestion, accompanied by pallor, lethargy, severe diarrhea, and hypotension, which required multiple fluid boluses. The patient was admitted to the intensive care unit for monitoring of FPIES complicated by fluid-responsive hypovolemic shock. Clinical improvement was observed within 24 h of re-initiating amino acid-based formula, and the patient was discharged after 48-72 h with complete resolution of symptoms.

Conclusions: A review of the literature revealed no prior reports of FPIES precipitated by viral infections. This case highlights a noteworthy temporal association between COVID-19 infection and the subsequent onset of FPIES in a patient who had previously tolerated cow's milk formula. Further studies are warranted to explore the possibility of viral infection induced FPIES.

Thymic stromal lymphopoietin (TSLP) is an alarmin mainly released by airway epithelial cells injured by many environmental noxious agents such as aeroallergens, respiratory viruses, bacteria, airborne pollutants and cigarette smoking. Airway expression levels of TSLP are related to both asthma severity and the extent of bronchial obstruction occurring in asthmatic patients. The pivotal pathogenic role played by TSLP in asthma is due to its capability of acting as an upstream driver of multiple cellular and molecular proinflammatory pathways, responsible for the development and persistence of both type 2 (T2-high) and T2-low asthma. Tezepelumab is a fully human monoclonal antibody which specifically binds to TSLP, thus impeding its interaction with the TSLP receptor complex expressed by immune/inflammatory and resident cells of the airways. By virtue of this very effective mechanism of action, tezepelumab prevents disease exacerbations and improves lung function. These positive outcomes have been verified by randomized clinical trials, as well as by preliminary real-life studies. The aim of this narrative review is to provide an overview of the pathogenic involvement of TSLP in asthma, followed by an updated discussion focused on the therapeutic effects induced by tezepelumab in severe asthmatic patients.