International Archives of Allergy and Immunology最新文献

Introduction: Hypersensitivity reactions (HSRs) to taxane- and platinum-based chemotherapeutic agents are common and may interrupt essential cancer therapy. Rapid drug desensitization (RDD) enables patients to continue treatment safely; however, detailed analyses directly comparing desensitization outcomes between taxanes and platinums remain relatively uncommon. The objective of this study was to describe the clinical characteristics of taxane- and platinum-induced HSRs and to compare desensitization outcomes, breakthrough reactions (BTRs), and graded-challenge success between these drug groups.

Methods: This retrospective study included 27 patients who underwent 30 desensitization procedures, comprising 94 RDD cycles. Standardized 8-, 12-, or 16-step RDD protocols were applied based on the severity of the index reaction and the clinical risk assessment. Demographic and clinical data, characteristics of index HSRs, BTRs during RDD, and outcomes of graded challenges were recorded and analyzed.

Results: Index HSRs most frequently occurred during the first or second infusion (66.6%) and were predominantly moderate in severity (53.3%). Cutaneous symptoms were present in 96.7% of reactions, and anaphylaxis occurred in 30%. Taxane HSRs developed significantly earlier than platinum reactions (69% vs. 24% during the first cycle, p = 0.003). The overall RDD success rate was 97.9%. Seventeen BTRs (18.1%) occurred, most of which were mild (82.4%) and limited to cutaneous involvement (100%). BTRs were significantly more common with platinums than with taxanes (34.8% vs. 2.1%, p < 0.001). Graded challenge was successful more often with taxanes than with platinums (53.8% vs. 17.6%, p = 0.045). No severe or life-threatening BTRs were observed.

Conclusion: RDD enabled the safe continuation of chemotherapy with both taxanes and platinums, with high success rates and infrequent, mostly mild BTRs. Platinum desensitizations carried a higher BTR risk, whereas selected taxane-allergic patients successfully transitioned to graded challenge. These findings support RDD as an effective strategy for managing chemotherapy-induced HSRs and highlight the need for individualized, risk-based protocol selection in clinical practice.

Introduction: Tests for dog and cat allergen molecules might be useful to characterize individuals with clinical symptoms in unselected population samples. The aim of this study was to present prevalence data and to investigate airway symptoms to cats and dogs in relation to sensitization to cat and dog allergen molecules.

Methods: In a random sample from a population-based cohort aged 19 years, 595 subjects were tested for sensitization to airborne allergens. Sera from subjects with IgE levels of >0.10 kU/L to cat, dog, or horse were further analyzed by microarray (ImmunoCAP™ ISAC 112) for dog molecules Can f 1-6 and cat molecules Fel d 1, 2, and 4. Fel d 7 was analyzed with ImmunoCAP™. Information about symptoms of asthma and rhinoconjunctivitis upon cat and dog exposure was obtained by a structured interview.

Results: The most prevalent (51.6%) sensitizing dog allergen molecule was Can f 5. The prevalence of asthma upon dog contact increased from 0.9% in individuals negative to all tested dog molecules to 40% in individuals sensitized to 6 dog molecules. The prevalence of asthma upon dog contact was related to the number of dog lipocalin sensitizations independent of sensitization to Can f 5, whereas for rhinoconjunctivitis Can f 5 co-sensitization played a role. The most prevalent (91.2%) sensitizing cat molecule was Fel d 1 and co-sensitization to up to three molecules increased the prevalence of asthma when exposed to cat.

Conclusion: In individuals sensitized to cat as in individuals sensitized to dog, the prevalence of allergic symptoms increased with the number of sensitizing allergen molecules. Individuals sensitized to dog had more complex sensitization patterns to allergen molecules compared to those sensitized to cat. Asthma upon dog exposure was mostly associated with dog lipocalin sensitization, whereas Can f 5 sensitization increased the risk of rhinoconjunctivitis.

Introduction: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) has a substantial impact on patients' health-related quality of life (HRQoL). While generic instruments are frequently used for assessment, they may not fully capture the disease-specific burden. This study aimed to evaluate HRQoL in patients with HAE-C1INH types I and II using validated, angioedema-specific tools. The aims of the study were to assess HRQoL and disease control in patients with HAE-C1INH using validated angioedema-specific tools and secondarily to explore the association between attack localization and domain-specific quality-of-life impairments.

Methods: In this multicenter cross-sectional study, 82 patients with HAE-C1INH from six referral centers completed the Angioedema Control Test (AECT), Angioedema Activity Score (AAS)-28, and Angioedema Quality of Life questionnaire (AE-QoL). Family screening was conducted among those who consented.

Results: Patients experiencing attacks in the extremities (p < 0.001) and laryngeal/pharyngeal regions (p = 0.028) had significantly lower AECT scores, indicating poorer disease control. Higher AAS-28 scores were associated with attacks in the extremities (p = 0.008), abdomen (p = 0.018), face/neck (p = 0.004), larynx/pharynx (p < 0.001), and tongue/uvula/palate (p < 0.001). AE-QoL scores revealed impaired quality of life across all attack locations. Subdomain analysis showed that abdominal attacks significantly impacted the functioning (p = 0.005) and food (p = 0.037) domains. Attacks involving the face/neck and larynx/pharynx were associated with substantial impairment in fatigue/mood (p = 0.002, p = 0.003), functioning (p = 0.044, p = 0.002), and fears/shame (p = 0.039, p = 0.005) subdomains.

Conclusion: While attack frequency and disease control remain the primary determinants of HRQoL in HAE-C1INH, our findings indicate that attack localization is associated with distinct domain-specific quality-of-life impairments. Beyond assessing attack frequency, the use of disease-specific QoL tools allows for the identification of domain-specific impairments. Personalized treatment strategies targeting both symptom control and quality-of-life domains are essential for alleviating the long-term burden on patients and their families.

Introduction: Benralizumab, an anti-IL-5 receptor monoclonal antibody, induces near-complete eosinophil depletion and has demonstrated significant clinical benefits in severe eosinophilic asthma (SEA). Real-world data remain essential for evaluating its effectiveness outside controlled trial settings. The aim of the study was to assess the clinical, laboratory, and functional outcomes of benralizumab over 32 weeks in a real-life cohort of SEA patients in Türkiye, following its recent national approval.

Methods: This retrospective study included biologic-naïve adults with SEA who initiated benralizumab between November 2023 and February 2025 and completed at least six consecutive doses. Peripheral blood eosinophil count (PBEC), clinically significant exacerbations (CSEs), Asthma Control Test (ACT) scores, and spirometric parameters were evaluated at baseline and week 32. Patients were classified as responders (ACT ≥20 and no CSE) or nonresponders.

Results: Twenty-four patients (66.7% female; mean age 50.9 ± 13.1 years) were included. Median PBEC decreased from 800 (230-2,200) to 0 (0-100) cells/µL (p < 0.001). Median annual CSE frequency declined by 67% (p < 0.001). ACT scores improved from 9 (5-24) to 22 (9-25) (p < 0.001). Mean forced expiratory volume in 1 s (FEV₁) increased from 1,719 ± 768 mL to 2,165 ± 831 mL (p < 0.001), while forced vital capacity (FVC) showed significant improvement. Forced expiratory flow between 25% and 75% of the FVC (FEF_25-75) exhibited a nonsignificant trend toward increase. Sixteen patients (66.7%) were classified as responders. Responders had higher baseline PBEC, FEV₁, and FEF_25-75 values. Benralizumab was well tolerated, with only two mild adverse events observed.

Conclusion: Benralizumab provided substantial improvements in eosinophilic inflammation, exacerbation frequency, symptom control, and lung function over 32 weeks in a real-life SEA cohort. These findings support benralizumab as an effective and well-tolerated therapeutic option in routine clinical practice.

Introduction: Cow's milk protein allergy (CMPA) affects approximately 2-3% of healthy children. The natural history of CMPA is poorly described in preterm infants. The aim of the study was to determine disease characteristics and long-term natural history of CMPA in preterm infants.

Methods: This was a retrospective cohort study of Clalit Health Services (CHS) members (the largest of 4 integrated health care organizations in Israel). The medical records of children, who developed, as preterm infants, symptoms suggestive for CMPA during their hospitalization at the neonatal intensive care unit between June 2009 and June 2020 and subsequently were attending primary care clinics of the CHS in Northeastern Israel, were retrospectively reviewed for clinical manifestation and laboratory variables at disease onset and during follow-up.

Results: Among 141 preterm infants (mean gestational age 31 weeks, median follow-up 3.4 years), CMPA persistence was 16% at 1 year, 1.8% at 3 years, and 1.5% at 6 years. Atopic conditions developed at 39%, with asthma being most frequent (31%). Cesarean delivery was associated with higher risk of subsequent atopic disease (HR 1.22, p = 0.009).

Conclusions: CMPA in preterm infants is often resolved by 1 year. Accurate diagnosis and earlier reintroduction of cow milk protein may improve outcomes and reduce unnecessary interventions.

Introduction: Lung adenocarcinoma (LUAD) is a common and fatal form of lung cancer, with varying expressions of midkine (MDK) and tissue inhibitor of metalloproteinase (TIMP1) across different cancers. However, their specific roles in LUAD progression and tumor immunity remain unclear.

Methods: We analyzed RNA-seq data from TCGA using the ggpubr R package to compare MDK and TIMP1 expression in normal versus LUAD tissues. This was validated through qRT-PCR and Western blot. LUAD patients were categorized into high and low expression groups for MDK and TIMP1, and their impacts on overall survival (OS), disease-free interval (DFI), progression-free interval (PFI), and disease-specific survival (DSS) were assessed using Kaplan-Meier curves and receiver operation characteristic curves. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for 50 genes similar to MDK and TIMP1, and a gene-gene interaction network was created with GeneMANIA, examining differentially expressed genes across both expression groups. We also evaluated the mutational landscape and immune cell infiltration correlations. Finally, the relationship between MDK, TIMP1 and immune cells was explored by immunohistochemical (IHC) experiments.

Results: MDK and TIMP1 were significantly overexpressed in LUAD. Patients with low MDK and TIMP1 expressions had better OS, DFI, DSS, and PFI. The AUC values for MDK and TIMP1 were 0.943 and 0.875, respectively, with TIMP1 identified as a risk factor for OS. Genes similar to MDK were enriched in the Proteasome pathway, while those akin to TIMP1 were linked to endopeptidase activity. No survival impact was noted from mutations in these genes. Higher expression of MDK and TIMP1 correlated with reduced tumor purity and altered immune scores, suggesting increased immune dysfunction in the high TIMP1 group. IHC results showed that when MDK and TIMP1 expression levels were higher, B cell and TREG cell infiltration was stronger, but macrophage infiltration was weaker.

Conclusion: MDK and TIMP1 significantly influence the prognosis and progression of LUAD and immune cell infiltration, highlighting their potential as targets for immunotherapy.

Introduction: To determine threshold concentrations of pollen inducing symptoms in seasonal allergic rhinitis patients has been a challenge for decades. Allergen challenge chambers (ACC) allow a controlled, reproducible experimental design to address this problem. Hitherto, ACCs were only run with high pollen concentrations.

Methods: The Fraunhofer ACC was technically modified to deploy very low pollen concentrations. Then, adults with birch pollen-induced allergic rhinitis were challenged with varying birch pollen concentrations using a patient-blinded, sham challenge-controlled, part-randomized, titrate-to-effect clinical study setting. Mean increase in Total Nasal Symptom Score (TNSS) ≥0.55 compared to sham challenge was regarded as minimal clinically important difference (MCID). Further endpoints were nasal secretion weight, exhaled nitric oxide (FeNO), and inflammatory cells from nasal lavage.

Results: Fifteen participants with mild to moderate allergic rhinitis participated in the experimental study part (mean age 45 years [22-64]; 7 females). Mean TNSS was: 1.08 at 0 pollen/m3; 1.05 at 10 pollen/m3; 1.2 at 50 pollen/m3; 1.74 at 100 pollen/m3; 1.61 at 200 pollen/m3; 2.79 at 1,000 pollen/m3. MCID of TNSS was observed at 100, 200, and 1,000 pollen/m3. More than half of the study population showed a lack of response at 10, 50, and 200 pollen/m3. Nasal secretion increased slightly with concentration. No clinically meaningful results could be derived from FeNO and inflammatory cells.

Conclusions: The applied technical modification of the Fraunhofer ACC produced stable, low pollen concentrations. Based on mean TNSS data, the threshold concentration for inducing symptoms with birch pollen was 50-100 pollen/m3.

Introduction: Limited data are available regarding the effectiveness of different omalizumab-dosing strategies in childhood chronic spontaneous urticaria (CSU). This study aimed to investigate the efficacy of omalizumab initiated at different doses in children and adolescents with CSU based on real-life data.

Methods: This study was conducted at five academic medical centers in Turkey. Patient data were obtained from their file data. Omalizumab treatment was initiated at a dose of 150 mg every 4 weeks in 37 (60.7%) patients (group 1) and 300 mg in 24 (39.3%) patients (group 2).

Results: The mean age of patients was 14.4 ± 2.6 years (6.3-18 years), and female-to-male ratio was 2.2 (42/19). There was no difference between the mean initial UAS7 scores of groups 1 and 2 (34 ± 8.8 and 34.6 ± 9.1, respectively) (p = 0.854). Groups 1 and 2 achieved an urticaria-free or well-controlled status at rates of 75.7% (n = 28) and 87.5% (n = 21), respectively, during the treatment period (p = 0.334). Group 2 achieved urticaria-free or well-controlled status in a shorter time than group 1 (median: 1 month [1-3 months] and median: 2 months [1-4 months], respectively) (p = 0.036). The rate of patients who achieved urticaria-free status during the study period was 59.5% (n = 22) and 87.5% (n = 21) in groups 1 and 2, respectively (p = 0.023). Seven patients in group 1 (31.8%) and 2 patients in group 2 (9.5%) experienced recurrence (p = 0.132). At the last evaluation, more patients in group 2 (83.3%, n = 20) were urticaria-free than in group 1 (48.6%, n = 18) (p = 0.008). A patient had an exacerbation of urticaria associated with omalizumab within the first 24 h of the first dose, but this complication was not repeated. Other than dizziness in 1 patient, no different side effects were seen in our cohort of patients.

Conclusion: Omalizumab is an effective and reliable treatment option for childhood CSU. Urticaria-free or well-controlled status can be achieved in a shorter time by initiating treatment with a 300 mg/4 week regimen. Although this dose may need to be increased in most cases, control can be achieved with a dose of 150 mg/4 weeks in a considerable number of patients.

Introduction: This study was conducted to investigate how changes in self-perception in adolescents with chronic atopic diseases develop over time; and the influences of parenting, peer interactions, and school adaptation on these changes.

Methods: Data from the Korean Children & Youth Panel Survey (2010-2016) were analyzed, including 874 individuals with atopic diseases. Latent growth modeling was applied to analyze the changing pattern of self-perception and the factors affecting it.

Results: The self-perception scores indicated a tendency to increase as time passed. High levels of positive and low levels of negative parenting styles, as well as strong school adaption and peer attachment, impacted the high self-perception scores of adolescents who suffered from chronic conditions at various points in time over the longitudinal school ages.

Conclusion: The study highlights the importance of positive parenting, peer relationships, and school adaptation for youth with chronic atopic conditions. Efforts to improve these areas should continue.

Introduction: Allergen avoidance, the most effective strategy against allergic diseases, does not readily apply to indoor inhalant allergens. Capturing and eliminating allergens in the air could be an effective strategy. In this study, we tested the capability of titanium dioxide (TiO₂) to degrade allergens upon activation by a photocatalyst. House dust mite (HDM), cat, and oak pollen extracts were incubated with TiO₂ powder for 24 h in either dark or light exposure.

Methods: Changes in protein and allergen content (Der f 1, Fel d 1, and Que ac 1) were investigated by the Bradford assay and a 2-site ELISA. Protein profiles and IgE-reactive components were examined by SDS-PAGE and IgE immunoblotting. Inhibition ELISA was performed to evaluate allergenicity.

Results: Regarding protein concentrations, 69.9% of HDM, 27.1% of cat, and 21.5% of oak pollen proteins were degraded by TiO₂ compared to the allergen extracts incubated in the dark without TiO₂. More specifically, 96.6% of Der f 1 and 81.2% of Fel d 1 were degraded by investigatory rutile TiO₂, as measured by ELISA. However, no significant degradation of Que ac 1 was observed. Immunoblot analyses using mouse monoclonal antibodies against each allergen and IgE antibodies from patients' sera showed diminished allergen bands. In the inhibition ELISA of HDM extract containing various proteases, 87.1% and 96.5% of IgE reactivity was reduced by TiO₂, whereas 47.0% of self-degradation was observed.

Conclusion: TiO₂ eliminated each allergen molecule at a different degradation rate. TiO₂ may be useful in reducing indoor allergenic molecules. However, more detailed studies are needed to optimize its efficacy.