World Allergy Organization Journal最新文献

Drug provocation tests (DPTs) are also used in some patients with a history of a contrast medium (CM)-hypersensitivity reaction. Since the use of contrast agents requires special knowledge that is present in radiology but not necessarily in allergology, this overview should close the knowledge gaps. The literature, and the package inserts of the industry dealing with DPTs in contrast hypersensitivity reactions was analyzed and the results presented. Historical analyses revealed that provocation tests were already done in the past, and called pre-testing. Due to disadvantages, this diagnostic tool was abandoned. A few years later, DPT was introduced as an innovative diagnostic procedure. The DPT has the 3 main disadvantages: a missing standardization, patients at risk (such as compromised renal function) are rarely taken into account, and a negative DPT does not exclude a subsequent CM reaction. DPTs (formerly called pre-testing) are a well-known method for diagnosing CM-related hypersensitivity reactions. Since the disadvantages of this diagnosis outweigh the advantages, we propose replacing DPT with routine contrast-enhanced imaging examination in radiology.

Background

Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires.

Methods

We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months.

Results

The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except “cough,” were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P < 0.05). The total scores and subscores of all domains of the QLQAKA, SAQ, and EQ-5D improved significantly 6 months after biologic therapy but not after conventional therapy. The total QLQAKA, SAQ, and EQ-5D scores improved after 6 months in the anti-IL-5 (P < 0.05) and anti-IL-4/IL-13 (P < 0.05) treatment groups with no significant difference between groups (P > 0.05).

Conclusion

QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.

Background

Allergic rhinitis (AR) is a nasal disorder characterized by the simultaneous manifestation of at least 2 out of 4 possible symptoms: rhinorrhea, nasal itching, nasal pruritus, and sneezing. Presently, among Chinese young adults from Singapore, we characterised AR phenotypes, established Total Nasal Symptom Score (TNSS) baselines, and examined the management of AR.

Methods

Participants completed an investigator-administered International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and underwent a skin prick test (SPT). Individuals exhibiting sensitization during the SPT while having at least 2 rhinitis symptoms were identified as AR cases, then categorized into Allergic Rhinitis in Asthma (ARIA) classifications.

Results

There were 9323 subjects analyzed. AR prevalence was estimated at 35.4%. Rhinorrhea was perceived as the most severe (mean Nasal Symptom Score (mNSS) ± SD: 1.42 ± 0.74), while nasal pruritus was the least severe (mNSS ± SD: 1.24 ± 0.68). Among moderate-severe AR (68.1%), most were affected by either troublesome symptoms (27.7%) or sleep disturbances (18.4%). By ARIA classes, 26.6% were mild intermittent, 5.4% were mild persistent, 50.3% were moderate-severe intermittent, and 17.6% were moderate-severe persistent. The mean TNSS (mTNSS) of AR cases was 4.43 (SD = 2.49) and between AR classifications, the mTNSS was significantly different. Notably, a large proportion of AR cases remained undiagnosed (85.2%), untreated (72.5%), or both (65.4%); 19.8% self-medicated for AR.

Conclusions

There was a significant difference in TNSS of the AR phenotypes, and among phenotypes with a higher mTNSS, a large proportion remained untreated, undiagnosed, or both. The evidence indicates an existing burden of AR among Chinese young adults in Singapore which is notably undermanaged.

Background

Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR.

Methods

Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites.

Results

we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%).

Conclusion

In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality.

Trial registration

ANZCTR ACTRN12619000241134. Registered 19 February 2019.

Background

Cardiovascular diseases (CVDs) have been associated with atopic dermatitis (AD), including in Korean patients. Previous studies on AD have primarily focused on patients of European ancestry, while the Asian endotype exhibits distinct characteristics. This study aimed to characterize the blood proteomic signature of Korean patients with moderate-to-severe AD, with an emphasis on proteins related to CVDs.

Methods

A total of 78 participants, including 39 patients with moderate-to-severe AD and 39 age- and sex-matched healthy controls, were enrolled. Blood proteomics analysis was performed using the Olink CVD II panel, which measures the expression levels of 92 proteins associated with CVDs.

Results

Unsupervised hierarchical clustering revealed 44 upregulated and 5 downregulated proteins in AD patients compared to healthy controls. Principal component analysis (PCA) effectively distinguished AD patients from healthy subjects based on the complete set of proteins or the subset of upregulated proteins. A multiple linear regression model comprising CCL17 and FGF21 showed a strong correlation with disease severity (R = 0.619). Correlation analysis identified 25 highly correlated proteins, including STK4, ITGB1BP2, and DECR1, which were newly found to be upregulated in Korean AD patients. Pathway analysis highlighted the involvement of these proteins in vascular system, inflammation, and lipid metabolism pathways.

Conclusion

The blood proteomic profile of moderate-to-severe AD patients in Korea differed from healthy controls using the CVD II panel. This study provides potential biomarkers for the AD-CVD association and insights into the pathways contributing to this relationship in the Korean population.

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. Exosomes were involved in different inflammatory diseases, but their roles in CRSwNP were poorly explored.

Method

We collected serum samples from 8 CRSwNP patients and 8 healthy controls (HC) and isolated their exosomes. MiRNA sequencing was performed for the exosome samples and differentially expressed miRNAs were identified. The top 3 differentially expressed exosomal miRNAs were confirmed in 2 validation cohorts, and their diagnostic values, predictive values for eosinophilic endotype, and recurrence were evaluated.

Results

Distinctive serum exosomal miRNA profiles were observed between CRSwNP and HC groups. Reverse transcription-polymerase chain reaction results in the first validation cohort revealed that serum exosomal miR-141-3p levels were increased, and miR-18a-5p and miR-3679-5p levels were decreased in the CRSwNP group compared to the HC group. These 3 miRNAs were further validated in the second validation cohort, and the results showed that miR-141-3p levels were elevated and miR-3679-5p levels were reduced in the serum exosomes in the eosinophilic CRSwNP group in comparison with the non-eosinophilic CRSwNP group. Receiver operating characteristic (ROC) curves highlighted that exosomal miR-141-3p and miR-3679-5p exhibited promising values for predicting the eosinophilic endotype. The patients in the second cohort were followed up for 2 years, and categorized into recurrence and non-recurrence groups. The serum exosomal miR-141-3p levels were increased and miR-3679-5p levels were reduced in the recurrence group in comparison with the non-recurrence group. ROC curves and Kaplan-Meier survival analysis revealed significant associations between the levels of exosomal miR-141-3p and miR-3679-5p and the risk of postoperative recurrence.

Conclusions

This study identified unique miRNA expression patterns in serum exosomes of CRSwNP patients. Circulating exosomal miR-141-3p and miR-3679-5p emerged as novel biomarkers for diagnosing CRSwNP, predicting the eosinophilic endotype, and forecasting postoperative recurrence.

The presence of angioedema, or deep skin swelling, in addition to hives (wheals) in patients with chronic spontaneous urticaria (CSU) can complicate disease management. There is evidence that omalizumab is effective for patients with CSU with angioedema, but the time to a clinically meaningful response has not been assessed. This post hoc analysis examined data from the phase 3, randomized, double-blind ASTERIA I and ASTERIA II studies: patients with CSU with hives were grouped by presence (n = 216) or absence of angioedema (n = 265) at baseline. The time to minimally important difference (MID, change from baseline of ≥11 points) in weekly Urticaria Activity Score (UAS7) was analyzed using Kaplan-Meier analyses. Median time to MID for omalizumab 300 mg was similar in patients with and without angioedema. Median time to MID for omalizumab 150 mg was similar to 300 mg for patients without angioedema, and was longer for patients with angioedema. Therefore, the response to omalizumab for patients with CSU with angioedema was dose dependent. We recommend that the best approach for clinicians, in line with guidelines, would be initial administration of omalizumab 300 mg every 4 weeks for all patients.

Clinical trials registration

Clinicaltrials.gov NCT01287117 (registered 27 January 2011) and NCT01292473 (registered 7 February 2011).

Background

Refractory anaphylaxis poses an ongoing, lethal hypersensitivity response that unpredictably involves multiple organs despite appropriate intramuscular (IM) adrenaline injections. Studies on the association of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) concerning anaphylactic severity have yet to be carried out. The study aimed to evaluate the association between blood PLR and NLR levels and refractory anaphylaxis.

Methods

We carried out a retrospective cross-sectional study in which medical records of patients with anaphylaxis who sought urgent care at the Emergency Department (ED) of Tertiary Hospital in Hanoi, Vietnam, were evaluated. Based on the United Kingdom Resuscitation Council guidelines in 2021, patients were classified as refractory anaphylaxis if they needed more than two appropriate doses of intramuscular adrenaline for anaphylactic symptoms resolution. Clinical data and laboratory results were obtained in the medical records. Logistic regression analysis determined the association between contributing factors and refractory anaphylaxis.

Results

One-hundred eighteen adults (age 51.80 ± 18.25 years) were analyzed, including 38 refractory anaphylaxis patients (32.2%). Refractory anaphylaxis patients exhibited notably elevated platelet-to-lymphocyte ratio (PLR) (P = 0.006) and increased neutrophil-to-lymphocyte ratio (NLR) (P < 0.001) in comparison to non-refractory anaphylaxis patients. Receiver operating characteristic curve (ROC) analysis demonstrated an optimal PLR cutoff value of 129.5 (area under the ROC curve [AUC] 0.658, sensitivity 73.68%, specificity 61.25%, P = 0.004) and an optimal NLR cutoff value of 4 (AUC 0.736, sensitivity 65.79%, specificity 73.75%, P < 0.001) for refractory anaphylaxis. Multivariate logistic regression analysis revealed a PLR≥129.5 (OR = 4.83, 95% CI: 1.87–12.48) and an NLR≥4 (OR = 4.60, 95% CI: 1.86–11.41) were independently associated with refractory anaphylaxis.

Conclusion

Elevated PLR and NLR serve as independent indicators significantly associated with refractory anaphylaxis.

Background

Type 2 inflammation is the principal determinant of asthma in children, and it leads to the downstream activation of eosinophils (EOS), the production of immunoglobulin-E (IgE), and increased levels of fraction of exhaled nitric oxide (FeNO). Dupilumab received the approval for the treatment of uncontrolled severe Type 2 asthma in children.

Objective

The aim of this analysis was to calculate the Type 2 severe asthma paediatric population who would be eligible for treatment with dupilumab in Italy and characterize them by expected biomarker status.

Methods

The calculation of the dupilumab-eligible population employed a two-phase approach: 1) estimating the total number of children aged 6–11 years with uncontrolled severe asthma; and 2) stratifying the severe uncontrolled asthma population, based on appropriate biomarker levels, thus identifying patients eligible for treatment with dupilumab. The VOYAGE study provided the data for this analysis.

Results

The two-phase approach utilizing VOYAGE data revealed that the average number of paediatric patients with uncontrolled severe asthma was N = 1007. Stratification of these patients, as per VOYAGE data, indicated that the majority (N = 740; 73.5%) would have ≥2 elevated biomarkers, and over one-third patients (N = 434, 43.1%) would exhibit simultaneously elevated levels of EOS, FeNO and IgE. Of the paediatric patients, N = 864 were identified as eligible to dupilumab treatment, constituting 85.8% of the target population. Notably, nearly half eligible patients (N = 454) displayed elevated levels of both EOS and FeNO biomarkers, while the substantial majority (81.1%) exhibited at least an increase of EOS levels (N = 817). Patients with increased FeNO levels without a concurrent increase in EOS were less frequent (N = 47; 5.4% of the eligible population).

Conclusion

The simultaneous testing of multiple biomarkers during baseline patient assessment and disease follow-up is highly recommended. Utilizing cost-effective tests, physicians can estimate the prevalence of severe Type 2 asthma, categorize patients into distinct phenotypes (eosinophilic, allergic, or mixed), and consequently identify and prescribe the most suitable therapeutic interventions. This approach also facilitates the ongoing evaluation and adjustment of the treatment strategies based on individual patient responses.