Most biological and synthetic target-specific drugs for antihistamine-refractory chronic spontaneous urticaria (CSU) have not been compared head-to-head. This systematic review and network meta-analysis evaluated their relative efficacy and safety.
Methods
Searches were conducted on PubMed, Embase, Web of Science and Cochrane library databases to March 25, 2024 for randomized trials. A random-effects model was used to calculate the network estimates reported as mean differences (MD) and odds ratios (OR) with corresponding 95% CIs. Main outcomes included the weekly urticaria activity score (UAS7), adverse events (AEs) and serious adverse events (SAEs).
Results
23 randomized clinical trials with 6933 participants that compared 26 different interventions or dosages and placebos were included. Omalizumab 300 mg [MD −10.07, 95% CI (−11.35; −8.82)] continues to demonstrate superior efficacy compared with placebo. Remibrutinib, at doses of 35 mg once daily [MD −7.80, 95% CI (−12.76; −2.51)], 25 mg twice daily [MD −7.69, 95% CI (−9.85; −5.76)], and 10 mg twice daily [MD −7.61, 95% CI (−12.59; −2.47)], had the best overall performance for efficacy and safety. Dupilumab, fenebrutinib, and rilzabrutinib also showed greater efficacy than placebo. The results were similar for the proportion of patients who achieved UAS7 ≤ 6 or UAS7 = 0. No significant differences were found among all treatment comparisons for AEs and SAEs.
Conclusion
The findings of this study indicate that the biological agent omalizumab 300 mg and the oral small molecule remibrutinib at doses of 35 mg, 25 mg, or 10 mg are recommended for patients with antihistamine-refractory CSU.
Trial Registration
PROSPERO: CRD42024516289
大多数生物和合成靶向性药物治疗抗组胺难治性慢性自发性荨麻疹（CSU）尚未进行比较。本系统综述和网络荟萃分析评估了它们的相对疗效和安全性。方法检索PubMed、Embase、Web of Science和Cochrane图书馆数据库至2024年3月25日进行随机试验。使用随机效应模型计算网络估计，报告为平均差异（MD）和比值比（OR），相应的ci为95%。主要结局包括每周荨麻疹活动度评分（UAS7）、不良事件（ae）和严重不良事件（sae）。结果纳入了23项随机临床试验，6933名参与者，比较了26种不同的干预措施或剂量和安慰剂。Omalizumab 300 mg [MD - 10.07, 95% CI (- 11.35；−8.82)]继续表现出优于安慰剂的疗效。Remibrutinib，剂量为35mg，每日1次[MD - 7.80, 95% CI (- 12.76；−2.51)],25 mg，每日2次[MD−7.69,95% CI(−9.85；−5.76)]，10 mg每日2次[MD−7.61,95% CI(−12.59；−2.47)]，在疗效和安全性方面的综合表现最佳。Dupilumab， fenebrutinib和rilzabrutinib也显示出比安慰剂更好的疗效。UAS7≤6或UAS7 = 0的患者比例结果相似。在ae和SAEs的所有治疗比较中没有发现显著差异。结论本研究结果表明，300mg生物制剂omalizumab和35mg、25mg或10mg口服小分子remibrutinib可推荐用于抗组胺难治性CSU患者。试验注册号：CRD42024516289
{"title":"Biological and target synthetic treatments for chronic spontaneous urticaria: A systematic review and network meta-analysis","authors":"Zuotao Zhao, Yaqi Zheng, Xiaoting Song, Chengyue Peng, Shuanglu Liao, Peixin Zhang, Yen Tan, Xiaojie Huang, Litao Zhang","doi":"10.1002/clt2.70052","DOIUrl":"https://doi.org/10.1002/clt2.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Most biological and synthetic target-specific drugs for antihistamine-refractory chronic spontaneous urticaria (CSU) have not been compared head-to-head. This systematic review and network meta-analysis evaluated their relative efficacy and safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Searches were conducted on PubMed, Embase, Web of Science and Cochrane library databases to March 25, 2024 for randomized trials. A random-effects model was used to calculate the network estimates reported as mean differences (MD) and odds ratios (OR) with corresponding 95% CIs. Main outcomes included the weekly urticaria activity score (UAS7), adverse events (AEs) and serious adverse events (SAEs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>23 randomized clinical trials with 6933 participants that compared 26 different interventions or dosages and placebos were included. Omalizumab 300 mg [MD −10.07, 95% CI (−11.35; −8.82)] continues to demonstrate superior efficacy compared with placebo. Remibrutinib, at doses of 35 mg once daily [MD −7.80, 95% CI (−12.76; −2.51)], 25 mg twice daily [MD −7.69, 95% CI (−9.85; −5.76)], and 10 mg twice daily [MD −7.61, 95% CI (−12.59; −2.47)], had the best overall performance for efficacy and safety. Dupilumab, fenebrutinib, and rilzabrutinib also showed greater efficacy than placebo. The results were similar for the proportion of patients who achieved UAS7 ≤ 6 or UAS7 = 0. No significant differences were found among all treatment comparisons for AEs and SAEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings of this study indicate that the biological agent omalizumab 300 mg and the oral small molecule remibrutinib at doses of 35 mg, 25 mg, or 10 mg are recommended for patients with antihistamine-refractory CSU.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>PROSPERO: CRD42024516289</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuning Huang, Xue Zhang, Jinwen Wang, Wuping Bao, Chengjian Lv, Yingying Zhang, Xue Tian, Yan Zhou, Min Zhang
Background
Small airway dysfunction (SAD) is critical in chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO), impacting disease severity, acute exacerbation (AE) risk, and prognosis. Traditional spirometry may miss SAD due to its reliance on forced vital capacity.
Objective
This study investigates the role of impulse oscillometry system (IOS) for early detection, disease monitoring, and AE prediction.
Methods
Pathological specimens from 64 patients with normal lung function were divided into small airway pathological abnormalities (PAs, n = 38) and normal pathology (PN, n = 26). Logistic regression and receiver operating characteristic (ROC) curve analysis evaluated IOS's predictive value for SAD. Additionally, 37 healthy volunteers, 125 COPD patients, and 128 ACO patients underwent spirometry, IOS, FeNO, CT scans, and blood tests. Correlations between IOS and spirometry indices were evaluated. One-year follow-up of 140 patients assessed IOS's predictive capability for AE.
Results
ROC analysis indicated that R5 − R20 combined with FEF75%pred best predicted PAs (areas under the ROC curves [AUC] = 0.80). R5 − R20, with a cut-off of 0.09 kPa/[L/s], demonstrated 85.6% sensitivity and 72.9% specificity in distinguishing COPD from healthy individuals, and 89.1% sensitivity with 72.9% specificity for ACO. In COPD, R5 − R20 correlated strongly with spirometry indices (r = 0.60), while Fres correlated well in ACO (r = 0.48) for FEV1%pred ≥ 50%, with slightly weaker correlations for FEV1%pred < 50%. For predicting AE, a model combining R5 − R20, FEV1%Pred and body mass index had an AUC of 0.860 in COPD, while a model with Fres, FEV1%pred and fraction of exhaled nitric oxide achieved an AUC of 0.874 in ACO.
Conclusions
IOS is valuable for early detection, monitoring, and AE prediction in COPD and ACO, enhancing diagnostic precision.
{"title":"Role of impulse oscillometry in chronic obstructive pulmonary disease and asthma-chronic obstructive pulmonary disease overlap","authors":"Yuning Huang, Xue Zhang, Jinwen Wang, Wuping Bao, Chengjian Lv, Yingying Zhang, Xue Tian, Yan Zhou, Min Zhang","doi":"10.1002/clt2.70057","DOIUrl":"https://doi.org/10.1002/clt2.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Small airway dysfunction (SAD) is critical in chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO), impacting disease severity, acute exacerbation (AE) risk, and prognosis. Traditional spirometry may miss SAD due to its reliance on forced vital capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study investigates the role of impulse oscillometry system (IOS) for early detection, disease monitoring, and AE prediction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pathological specimens from 64 patients with normal lung function were divided into small airway pathological abnormalities (PAs, <i>n</i> = 38) and normal pathology (PN, <i>n</i> = 26). Logistic regression and receiver operating characteristic (ROC) curve analysis evaluated IOS's predictive value for SAD. Additionally, 37 healthy volunteers, 125 COPD patients, and 128 ACO patients underwent spirometry, IOS, FeNO, CT scans, and blood tests. Correlations between IOS and spirometry indices were evaluated. One-year follow-up of 140 patients assessed IOS's predictive capability for AE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ROC analysis indicated that R5 − R20 combined with FEF<sub>75</sub>%pred best predicted PAs (areas under the ROC curves [AUC] = 0.80). R5 − R20, with a cut-off of 0.09 kPa/[L/s], demonstrated 85.6% sensitivity and 72.9% specificity in distinguishing COPD from healthy individuals, and 89.1% sensitivity with 72.9% specificity for ACO. In COPD, R5 − R20 correlated strongly with spirometry indices (<i>r</i> = 0.60), while Fres correlated well in ACO (<i>r</i> = 0.48) for FEV<sub>1</sub>%pred ≥ 50%, with slightly weaker correlations for FEV<sub>1</sub>%pred < 50%. For predicting AE, a model combining R5 − R20, FEV<sub>1</sub>%Pred and body mass index had an AUC of 0.860 in COPD, while a model with Fres, FEV<sub>1</sub>%pred and fraction of exhaled nitric oxide achieved an AUC of 0.874 in ACO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IOS is valuable for early detection, monitoring, and AE prediction in COPD and ACO, enhancing diagnostic precision.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical Trial Registration</h3>\u0000 \u0000 <p>No. ChiCTR2400089625, www.chictr.org.cn.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyo-In Rhyou, Sung-Ryeol Kim, Jae-Woo Jung, Sae-Hoon Kim, Ji-Hyang Lee, Hye Jung Park, Kyung-Hee Park, Hee-Sun Park, Eun-Hee Chung, Gil-Soon Choi, Sujeong Kim, Min-Suk Yang, Jung-Yeon Shim, Young-Il Koh, Da-Woon Sim, Jae-Hyun Lee, Young-Hee Nam, Hye-Ryun Kang
Background
Drug hypersensitivity reaction (DHR) poses significant challenges in clinical practice, with some patients experiencing more severe reactions upon re-exposure. Understanding the factors contributing to escalation into more severe reactions is crucial for improving patient safety. This study aimed to investigate the clinical characteristics and risk factors associated with the progression from non-severe DHR to anaphylaxis.
Methods
A multicenter retrospective study was conducted using data from a drug-induced anaphylaxis registry across 10 university hospitals in Korea. Clinical data, including information on culprit drugs, DHR history, and the severity of reactions, were assessed.
Results
Among 494 cases of drug-induced anaphylaxis, 417 cases (84.4%) occurred without prior DHR, while 77 cases (15.6%) had a history of non-severe DHR. Of these, 43 cases had a previous DHR to a drug of the same class, and 34 cases involved DHR to drugs of different classes. In the group with prior DHR to a drug of the same class, anaphylaxis occurring in daily life was significantly more common compared to those reacting to a different class of drug or those with no prior DHR (48.8% vs. 23.5% or 22.5%, p = 0.008 and < 0.001, respectively). Non-steroidal anti-inflammatory drugs (NSAIDs), H2 blockers, and penicillins were identified as risk factors for anaphylaxis evolving from non-severe DHR.
Conclusion
Enhanced vigilance is required for patients with a history of non-severe DHR to NSAIDs, H2 blockers, and penicillins as re-exposure may lead to the progress to anaphylaxis.
{"title":"Clinical characteristics and risk factors for escalation to anaphylaxis from non-severe drug hypersensitivity reaction","authors":"Hyo-In Rhyou, Sung-Ryeol Kim, Jae-Woo Jung, Sae-Hoon Kim, Ji-Hyang Lee, Hye Jung Park, Kyung-Hee Park, Hee-Sun Park, Eun-Hee Chung, Gil-Soon Choi, Sujeong Kim, Min-Suk Yang, Jung-Yeon Shim, Young-Il Koh, Da-Woon Sim, Jae-Hyun Lee, Young-Hee Nam, Hye-Ryun Kang","doi":"10.1002/clt2.70047","DOIUrl":"https://doi.org/10.1002/clt2.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Drug hypersensitivity reaction (DHR) poses significant challenges in clinical practice, with some patients experiencing more severe reactions upon re-exposure. Understanding the factors contributing to escalation into more severe reactions is crucial for improving patient safety. This study aimed to investigate the clinical characteristics and risk factors associated with the progression from non-severe DHR to anaphylaxis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A multicenter retrospective study was conducted using data from a drug-induced anaphylaxis registry across 10 university hospitals in Korea. Clinical data, including information on culprit drugs, DHR history, and the severity of reactions, were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 494 cases of drug-induced anaphylaxis, 417 cases (84.4%) occurred without prior DHR, while 77 cases (15.6%) had a history of non-severe DHR. Of these, 43 cases had a previous DHR to a drug of the same class, and 34 cases involved DHR to drugs of different classes. In the group with prior DHR to a drug of the same class, anaphylaxis occurring in daily life was significantly more common compared to those reacting to a different class of drug or those with no prior DHR (48.8% vs. 23.5% or 22.5%, <i>p</i> = 0.008 and < 0.001, respectively). Non-steroidal anti-inflammatory drugs (NSAIDs), H2 blockers, and penicillins were identified as risk factors for anaphylaxis evolving from non-severe DHR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Enhanced vigilance is required for patients with a history of non-severe DHR to NSAIDs, H2 blockers, and penicillins as re-exposure may lead to the progress to anaphylaxis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Semra Demir, Müge Olgaç, Osman Ozan Yeğit, İlkim Deniz Toprak, Mehmet Erdem Çakmak, Merve İğde Hormet, Nida Öztop, Pelin Korkmaz, Şule Kamacı Çelik, Deniz Eyice Karabacak, Nevzat Kahveci, Işıl Göğem İmren, Bircan Erden, Raif Coşkun, Pelin Karadağ, Derya Ünal, Aslı Gelincik
Background/Aim
Misdiagnosis of hereditary angioedema (HAE) leads to inappropriate management of the attacks. A scoring system that anticipates diagnosis can be beneficial for clinicians who are unfamiliar with angioedema. This study aims to develop a practical scoring system for use during acute attacks to predict HAE in patients with recurrent angioedema (RAE).
Method
To predict HAE, nine HAE experts unanimously identified five predictive items (PIs); absence of urticaria, presence of abdominal pain episodes, family history, early onset of attacks and previous unresponsiveness to anti-histaminergic treatments. The researchers questioned 106 patients with HAE and 155 patients with mast cell-mediated angioedema (MMAE) about PIs. A score was attributed to each significant PI based on OR values obtained through logistic regression analysis. The cut-off point for the prediction of HAE and its sensitivity and specificity were determined by ROC curve analysis.
Results
In a univariate analysis, all items showed significant differences between HAE and MMAE patients. Regression analysis attributed scores as follows: 23 points for the absence of urticaria, 11 points for the abdominal pain episodes, 9 points for family history, and 53 points for unresponsiveness to antihistaminergic treatments. No score was attributed to early onset of age (p > 0.05). The ROC analysis revealed an area under the curve of 0.990, with a total score of ≥38 demonstrating the best sensitivity (96.4%) and specificity (96.1%).
Conclusions
HAEps is a valuable tool for diagnosing HAE in patients with RAE. A score of 38 or more indicates the possible presence of HAE with substantial sensitivity and specificity.
{"title":"Prediction of hereditary angioedema during attacks in patients with recurrent angioedema: Awareness at a glance with the hereditary angioedema prediction score","authors":"Semra Demir, Müge Olgaç, Osman Ozan Yeğit, İlkim Deniz Toprak, Mehmet Erdem Çakmak, Merve İğde Hormet, Nida Öztop, Pelin Korkmaz, Şule Kamacı Çelik, Deniz Eyice Karabacak, Nevzat Kahveci, Işıl Göğem İmren, Bircan Erden, Raif Coşkun, Pelin Karadağ, Derya Ünal, Aslı Gelincik","doi":"10.1002/clt2.70040","DOIUrl":"https://doi.org/10.1002/clt2.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Aim</h3>\u0000 \u0000 <p>Misdiagnosis of hereditary angioedema (HAE) leads to inappropriate management of the attacks. A scoring system that anticipates diagnosis can be beneficial for clinicians who are unfamiliar with angioedema. This study aims to develop a practical scoring system for use during acute attacks to predict HAE in patients with recurrent angioedema (RAE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>To predict HAE, nine HAE experts unanimously identified five predictive items (PIs); absence of urticaria, presence of abdominal pain episodes, family history, early onset of attacks and previous unresponsiveness to anti-histaminergic treatments. The researchers questioned 106 patients with HAE and 155 patients with mast cell-mediated angioedema (MMAE) about PIs. A score was attributed to each significant PI based on OR values obtained through logistic regression analysis. The cut-off point for the prediction of HAE and its sensitivity and specificity were determined by ROC curve analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In a univariate analysis, all items showed significant differences between HAE and MMAE patients. Regression analysis attributed scores as follows: 23 points for the absence of urticaria, 11 points for the abdominal pain episodes, 9 points for family history, and 53 points for unresponsiveness to antihistaminergic treatments. No score was attributed to early onset of age (<i>p</i> > 0.05). The ROC analysis revealed an area under the curve of 0.990, with a total score of ≥38 demonstrating the best sensitivity (96.4%) and specificity (96.1%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HAEps is a valuable tool for diagnosing HAE in patients with RAE. A score of 38 or more indicates the possible presence of HAE with substantial sensitivity and specificity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Szylling, Boleslaw Samoliński, Filip Raciborski, Konrad Furmańczyk, Mariola Chrzanowska, Oksana Wojas, Edyta Krzych-Fałta, Emilia Gawińska-Drużba, Krzysztof Samoliński, Jean Bousquet, Piotr Samel-Kowalik
Background
Monitoring adherence in chronic diseases remains a significant challenge. Allergic rhinitis (AR), one of the most common chronic conditions, serves as an excellent model for studying determinants of app use in monitoring adherence and health assessment during treatment. The Mask-air® app supports clinical decision-making by involving patients in symptom observation and promoting adherence to therapy. This study aimed to identify the defining characteristics of Mask-air® users, describe their disease phenotype and satisfaction with the app, and explore reasons for discontinuation.
Materials and Methods
Adult patients 20–44 years old suffering from AR (n = 198) receiving care at an allergy outpatient clinic were invited to participate in a trial using the Mask-air® app. Investigators collected data on symptoms, administered treatments, and clinical evaluation results through questionnaires. At a follow-up visit (n = 163), these were compared, and patients were questioned about their satisfaction with the app. Patients presented their app records, and those who declined or stopped using the app were asked to provide reasons in a questionnaire.
Results
No distinguishing characteristics of Mask-air® users (n = 131) were identified compared with those who declined the app (n = 67). App readiness was analyzed according to age, socioeconomic status, disease severity, comorbidities, and therapeutic modality. Respondents were categorized into: those who did not install the app (17.7%), those who installed but did not use it (16.2%), and those who installed and evaluated it (66.2%), with 15.6% failing to produce symptom monitoring records. Overall, satisfaction ratings were high though patients were critical of the app's therapeutic aspect.
Conclusions
The study found no specific features distinguishing Mask-air® users, suggesting that it can be recommended to all patients regardless of gender, socioeconomic or educational status, or disease phenotype. However, with a dropout rate of nearly 50%, it is essential for clinicians to emphasize the app's benefits to improve adherence and engagement.
{"title":"Factors that influence user adherence of the Mask-air® application","authors":"Anna Szylling, Boleslaw Samoliński, Filip Raciborski, Konrad Furmańczyk, Mariola Chrzanowska, Oksana Wojas, Edyta Krzych-Fałta, Emilia Gawińska-Drużba, Krzysztof Samoliński, Jean Bousquet, Piotr Samel-Kowalik","doi":"10.1002/clt2.70054","DOIUrl":"https://doi.org/10.1002/clt2.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Monitoring adherence in chronic diseases remains a significant challenge. Allergic rhinitis (AR), one of the most common chronic conditions, serves as an excellent model for studying determinants of app use in monitoring adherence and health assessment during treatment. The Mask-air® app supports clinical decision-making by involving patients in symptom observation and promoting adherence to therapy. This study aimed to identify the defining characteristics of Mask-air® users, describe their disease phenotype and satisfaction with the app, and explore reasons for discontinuation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Adult patients 20–44 years old suffering from AR (<i>n</i> = 198) receiving care at an allergy outpatient clinic were invited to participate in a trial using the Mask-air® app. Investigators collected data on symptoms, administered treatments, and clinical evaluation results through questionnaires. At a follow-up visit (<i>n</i> = 163), these were compared, and patients were questioned about their satisfaction with the app. Patients presented their app records, and those who declined or stopped using the app were asked to provide reasons in a questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No distinguishing characteristics of Mask-air® users (<i>n</i> = 131) were identified compared with those who declined the app (<i>n</i> = 67). App readiness was analyzed according to age, socioeconomic status, disease severity, comorbidities, and therapeutic modality. Respondents were categorized into: those who did not install the app (17.7%), those who installed but did not use it (16.2%), and those who installed and evaluated it (66.2%), with 15.6% failing to produce symptom monitoring records. Overall, satisfaction ratings were high though patients were critical of the app's therapeutic aspect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study found no specific features distinguishing Mask-air® users, suggesting that it can be recommended to all patients regardless of gender, socioeconomic or educational status, or disease phenotype. However, with a dropout rate of nearly 50%, it is essential for clinicians to emphasize the app's benefits to improve adherence and engagement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Eosinophils and COVID-19: Insights into immune complexity and vaccine safety”","authors":"","doi":"10.1002/clt2.70056","DOIUrl":"https://doi.org/10.1002/clt2.70056","url":null,"abstract":"<p>Sahli W, Vitte J, Desnues B. Eosinophils and COVID-19: insights into immune complexity and vaccine safety. <i>Clin Transl Allergy</i>. 2025;e70050.</p><p>In Figure 1, the icons of monocyte and T cell and some labels were missing. This should have appeared as the following Figure 1.</p><p></p><p>We apologize for this error.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joaquim Mullol, Maria D'Amato, Eugenio de Corso, Joseph K. Han, Jody Tversky
Background
Type 2 (T2) inflammation, characterized by blood and airway eosinophilia, underlies severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP). In line with the Global Airways theory, SEA and CRSwNP frequently co-occur, creating a multimorbid phenotype. Separately, SEA and CRSwNP are burdensome: when concomitant, they compound each other, creating a more difficult-to-treat disease with increased complications.
Body
Current management approaches rarely control disease and are associated with substantial side-effects. Several recently developed anti-IL-5 monoclonal antibodies have shown efficacy in treating co-morbid SEA with CRSwNP by targeting T2 inflammation with systemic therapies. Of these, only benralizumab directly targets the IL-5 receptor-α, leading to rapid, sustained, near-complete eosinophil depletion. Analyses in patients with co-morbid SEA with CRSwNP are limited, although data from the ANDHI, XALOC-1, and RANS studies suggest benralizumab can effectively target inflammation underlying co-morbid disease.
Conclusion
Despite progress toward more effective therapies, treatment approaches remain siloed, with SEA and CRSwNP often managed separately. There is a need for the development of multidisciplinary approaches for treating patients with comorbid SEA with CRSwNP.
{"title":"Benralizumab and the integrated management of co-morbid severe eosinophilic asthma with chronic rhinosinusitis with nasal polyps","authors":"Joaquim Mullol, Maria D'Amato, Eugenio de Corso, Joseph K. Han, Jody Tversky","doi":"10.1002/clt2.70051","DOIUrl":"https://doi.org/10.1002/clt2.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 2 (T2) inflammation, characterized by blood and airway eosinophilia, underlies severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP). In line with the Global Airways theory, SEA and CRSwNP frequently co-occur, creating a multimorbid phenotype. Separately, SEA and CRSwNP are burdensome: when concomitant, they compound each other, creating a more difficult-to-treat disease with increased complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Body</h3>\u0000 \u0000 <p>Current management approaches rarely control disease and are associated with substantial side-effects. Several recently developed anti-IL-5 monoclonal antibodies have shown efficacy in treating co-morbid SEA with CRSwNP by targeting T2 inflammation with systemic therapies. Of these, only benralizumab directly targets the IL-5 receptor-α, leading to rapid, sustained, near-complete eosinophil depletion. Analyses in patients with co-morbid SEA with CRSwNP are limited, although data from the ANDHI, XALOC-1, and RANS studies suggest benralizumab can effectively target inflammation underlying co-morbid disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Despite progress toward more effective therapies, treatment approaches remain siloed, with SEA and CRSwNP often managed separately. There is a need for the development of multidisciplinary approaches for treating patients with comorbid SEA with CRSwNP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Z. P. Brandão, L. M. L. B. F. Lasmar, L. M. A. S. Pertence, M. I. R. Vieira, G. B. Lasmar, V. O. Ganem, E. V. Mancuzo, M. V. N. P. de Queiroz
Background
Although exacerbations are common in severe asthma, there have been few longitudinal studies evaluating their effect on lung function parameters. This study aimed to evaluate the impact of exacerbations on lung function in children and adolescents with severe asthma in Brazil.
Methods
This was a prospective study in which lung function parameters—forced vital capacity (forced vital capacity [FVC]), forced expiratory volume in 1 s (forced expiratory volume in 1 s [FEV1]), the FEV1/FVC ratio, and the forced expiratory flow between 25% and 75% of FVC (FEF25–75%), each expressed as a percentage of the predicted value—were measured at 3-month intervals for three years in 64 patients (6–18 years of age) with severe asthma. Multivariate regression models of longitudinal data were employed to assess the associations between exacerbations and other predictors show with lung function parameters.
Results
The mean duration of prior use of an inhaled corticosteroid together with a long-acting bronchodilator or other controller was 6.7 (SD 3.2) years. During the study period, 31 patients (48.5%) had exacerbations. We analyzed 479 pulmonary function tests and found no significant association between exacerbation and any of the lung function parameters: FEV1 (p = 0.90); FEF25–75% (p = 0.73); FEV1/FVC (p = 0.29); and FVC (p = 0.51). Passive smoking and being female were associated with mean FEV1 values that were 9.89% and 7.32% lower, respectively.
Conclusions
In children and adolescents with severe asthma who are using preventive treatment, exacerbations do not seem to be associated with impaired lung function.
{"title":"What is the influence of exacerbations on pulmonary function in pediatric and adolescent patients with severe asthma despite controller therapies?","authors":"A. Z. P. Brandão, L. M. L. B. F. Lasmar, L. M. A. S. Pertence, M. I. R. Vieira, G. B. Lasmar, V. O. Ganem, E. V. Mancuzo, M. V. N. P. de Queiroz","doi":"10.1002/clt2.70046","DOIUrl":"https://doi.org/10.1002/clt2.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although exacerbations are common in severe asthma, there have been few longitudinal studies evaluating their effect on lung function parameters. This study aimed to evaluate the impact of exacerbations on lung function in children and adolescents with severe asthma in Brazil.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a prospective study in which lung function parameters—forced vital capacity (forced vital capacity [FVC]), forced expiratory volume in 1 s (forced expiratory volume in 1 s [FEV1]), the FEV<sub>1</sub>/FVC ratio, and the forced expiratory flow between 25% and 75% of FVC (FEF<sub>25–75%</sub>), each expressed as a percentage of the predicted value—were measured at 3-month intervals for three years in 64 patients (6–18 years of age) with severe asthma. Multivariate regression models of longitudinal data were employed to assess the associations between exacerbations and other predictors show with lung function parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean duration of prior use of an inhaled corticosteroid together with a long-acting bronchodilator or other controller was 6.7 (SD 3.2) years. During the study period, 31 patients (48.5%) had exacerbations. We analyzed 479 pulmonary function tests and found no significant association between exacerbation and any of the lung function parameters: FEV<sub>1</sub> (<i>p</i> = 0.90); FEF<sub>25–75%</sub> (<i>p</i> = 0.73); FEV<sub>1</sub>/FVC (<i>p</i> = 0.29); and FVC (<i>p</i> = 0.51). Passive smoking and being female were associated with mean FEV<sub>1</sub> values that were 9.89% and 7.32% lower, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In children and adolescents with severe asthma who are using preventive treatment, exacerbations do not seem to be associated with impaired lung function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Markus Lilja, Anni Koskinen, Sari Hammarèn-Malmi, Anu Laulajainen-Hongisto, Jura Numminen, Jyri Myller, Seija Vento, Elina Penttila, Maija Hytönen, Paula Virkkula, Peter W. Hellings, Sven F. Seys, John Lee, Heini Huhtala, Johanna Sahlman, Sanna Toppila-Salmi
Objectives
The aim was to evaluate the predictive potential of Sinonasal Radiological (SR) and the Lund-Mackay (LM) score of sinus computed tomography (CT) scans on postoperative relapses of chronic rhinosinusitis (CRS).
Materials and Methods
CRS patients (n = 483, 12–80 years) underwent routine sinus CT scans. The SR score was defined by obstructed frontal recess (0 = no, 1 = yes) and visualization of middle and inferior turbinate (0 = anatomy can be easily visualized, 1 = anatomy cannot be easily visualized) on each side (a total of 0–6 points). Associations were analyzed by nonparametric, survival and Cox's proportional hazard models.
Results
Revision endoscopic sinus surgery (ESS) was performed in 133 (28.0%) patients on average (min–max) of 3.2 (0–12) years after performing the sinus CT scans. Of the 408 patients who underwent the baseline ESS, high preoperative SR or LM scores significantly predicted revision ESS (p < 0.001) and peroral corticosteroid courses purchased during the follow-up (p = 0.009 and p < 0.001, respectively for SR- and LM-scores). In multivariable analysis, both SR score and asthma and/or NSAID exacerbated respiratory disease (N-ERD) were significantly associated with revision ESS risk (p = 0.035, p = 0.007, respectively).
Conclusion
LM and SR and a history of asthma or N-ERD predict CRS relapses, which may help in decision-making.
{"title":"Radiological score, asthma and NSAID-exacerbated respiratory disease predict relapsing chronic rhinosinusitis","authors":"Markus Lilja, Anni Koskinen, Sari Hammarèn-Malmi, Anu Laulajainen-Hongisto, Jura Numminen, Jyri Myller, Seija Vento, Elina Penttila, Maija Hytönen, Paula Virkkula, Peter W. Hellings, Sven F. Seys, John Lee, Heini Huhtala, Johanna Sahlman, Sanna Toppila-Salmi","doi":"10.1002/clt2.70043","DOIUrl":"https://doi.org/10.1002/clt2.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The aim was to evaluate the predictive potential of Sinonasal Radiological (SR) and the Lund-Mackay (LM) score of sinus computed tomography (CT) scans on postoperative relapses of chronic rhinosinusitis (CRS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>CRS patients (<i>n</i> = 483, 12–80 years) underwent routine sinus CT scans. The SR score was defined by obstructed frontal recess (0 = no, 1 = yes) and visualization of middle and inferior turbinate (0 = anatomy can be easily visualized, 1 = anatomy cannot be easily visualized) on each side (a total of 0–6 points). Associations were analyzed by nonparametric, survival and Cox's proportional hazard models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Revision endoscopic sinus surgery (ESS) was performed in 133 (28.0%) patients on average (min–max) of 3.2 (0–12) years after performing the sinus CT scans. Of the 408 patients who underwent the baseline ESS, high preoperative SR or LM scores significantly predicted revision ESS (<i>p</i> < 0.001) and peroral corticosteroid courses purchased during the follow-up (<i>p</i> = 0.009 and <i>p</i> < 0.001, respectively for SR- and LM-scores). In multivariable analysis, both SR score and asthma and/or NSAID exacerbated respiratory disease (N-ERD) were significantly associated with revision ESS risk (<i>p</i> = 0.035, <i>p</i> = 0.007, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>LM and SR and a history of asthma or N-ERD predict CRS relapses, which may help in decision-making.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypoxia is a prevalent pathological process in chronic rhinosinusitis with nasal polyps (CRSwNP), leading to a cascade of pathological events, including epithelial-mesenchymal transition (EMT). However, the mechanisms underlying hypoxia-induced EMT remain unclear. This study aims to elucidate the mechanisms driving EMT under hypoxic conditions in CRSwNP.
Methods
Transcriptome and proteome analyses of hypoxia-treated human nasal epithelial cells (HNECs) were performed to identify key molecules and pathways. The expression of hypoxia-inducible factor-1α (HIF-1α), pyruvate dehydrogenase kinase (PDK1), lactate dehydrogenase A (LDHA), and EMT markers was assessed in nasal tissues from CRSwNP patients. In vitro, cultured HNECs were exposed to hypoxia and lactate, or overexpressed PDK1, to evaluate changes in EMT markers.
Results
Hypoxia activated the glycolysis-related pathway in HNECs, with PDK1 and LDHA identified as significantly upregulated glycolysis-related enzymes. The expression of PDK1 and LDHA was closely correlated with HIF-1α and EMT markers in nasal tissues. Hypoxia induced an increase in PDK1 and LDHA expression, lactate production, and EMT occurrence in HNECs. PDK1 overexpression or lactate stimulation also triggered EMT, while PDK1 inhibition attenuated hypoxia-induced EMT in HNECs.
Conclusions
This study is the first to reveal that hypoxia-induced activation of PDK1 plays a critical role in regulating EMT by promoting lactate production, thereby providing a potential therapeutic target for CRSwNP.
{"title":"Targeting PDK1: A novel approach to combat hypoxia-induced epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps","authors":"Sicen Pan, Mengyan Zhuang, Xiangdong Wang, Qinqin Zhang, Ting He, Ying Li, Jian Jiao, Luo Zhang","doi":"10.1002/clt2.70048","DOIUrl":"https://doi.org/10.1002/clt2.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hypoxia is a prevalent pathological process in chronic rhinosinusitis with nasal polyps (CRSwNP), leading to a cascade of pathological events, including epithelial-mesenchymal transition (EMT). However, the mechanisms underlying hypoxia-induced EMT remain unclear. This study aims to elucidate the mechanisms driving EMT under hypoxic conditions in CRSwNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Transcriptome and proteome analyses of hypoxia-treated human nasal epithelial cells (HNECs) were performed to identify key molecules and pathways. The expression of hypoxia-inducible factor-1α (HIF-1α), pyruvate dehydrogenase kinase (PDK1), lactate dehydrogenase A (LDHA), and EMT markers was assessed in nasal tissues from CRSwNP patients. In vitro, cultured HNECs were exposed to hypoxia and lactate, or overexpressed PDK1, to evaluate changes in EMT markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hypoxia activated the glycolysis-related pathway in HNECs, with PDK1 and LDHA identified as significantly upregulated glycolysis-related enzymes. The expression of PDK1 and LDHA was closely correlated with HIF-1α and EMT markers in nasal tissues. Hypoxia induced an increase in PDK1 and LDHA expression, lactate production, and EMT occurrence in HNECs. PDK1 overexpression or lactate stimulation also triggered EMT, while PDK1 inhibition attenuated hypoxia-induced EMT in HNECs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study is the first to reveal that hypoxia-induced activation of PDK1 plays a critical role in regulating EMT by promoting lactate production, thereby providing a potential therapeutic target for CRSwNP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号