Pub Date : 2024-11-21DOI: 10.1016/j.waojou.2024.101000
Duong Duc Pham, MD, PhD , Ji-Hyang Lee, MD, PhD , Hyouk-Soo Kwon, MD, PhD , Woo-Jung Song, MD, PhD , You Sook Cho, MD, PhD , Hyunkyoung Kim, MSc , Jae-Woo Kwon, MD, PhD , So-Young Park, MD, PhD , Sujeong Kim, MD, PhD , Gyu Young Hur, MD, PhD , Byung Keun Kim, MD, PhD , Young-Hee Nam, MD, PhD , Min-Suk Yang, MD, PhD , Mi-Yeong Kim, MD, PhD , Sae-Hoon Kim, MD, PhD , Byung-Jae Lee, MD, PhD , Taehoon Lee, MD, PhD , So Young Park, MD, PhD , Min-Hye Kim, MD, PhD , Young-Joo Cho, MD, PhD , Tae-Bum Kim, MD, PhD
Background
Limited understanding exists regarding the progression trajectory of severe eosinophilic asthma (SEA) patients on type 2 biologics therapies.
Objective
We aim to explore distinct longitudinal phenotypes of these patients based on crucial asthma biomarkers.
Methods
We enrolled 101 adult patients with SEA. Of these, 51 were treated with anti-IL5/IL5Rα or anti-IL5/IL5RαR antibody, and 50 with anti-IL-4Rα antibody. Multi-trajectory analysis, an extension of univariate group-based trajectory modeling, was used to categorize patients based on their trajectories of forced expiratory volume in 1 s (FEV1), blood eosinophil counts (BEC), and fractional exhaled nitric oxide (FeNO) levels at baseline, and after 1, 6, and 12 months of treatment. Associations between trajectory-based clusters and clinical parameters were examined.
Results
Among anti-IL5/IL5Rα antibody-treated patients, 2 clusters were identified. The cluster characterized by higher baseline BEC and lower FEV1 showed a better response, with improvements in FEV1 and reductions in BEC over time. Among anti-IL-4Rα antibody-treated, 3 clusters were identified. Clusters with moderate BEC and FeNO at baseline demonstrated better improvements in FEV1 and reductions in FeNO, despite increased BEC during follow-up. Conversely, individuals with extremely low FeNO and high BEC at baseline were more likely to experience poorer progression, demonstrating an increase in FeNO and a reduction in FEV1.
Conclusion
To optimally monitor treatment response in SEA patients on type 2 biologics, integrating longitudinal biomarker features is essential.
{"title":"Longitudinal multi-trajectory phenotypes of severe eosinophilic asthma on type 2 biologics treatment","authors":"Duong Duc Pham, MD, PhD , Ji-Hyang Lee, MD, PhD , Hyouk-Soo Kwon, MD, PhD , Woo-Jung Song, MD, PhD , You Sook Cho, MD, PhD , Hyunkyoung Kim, MSc , Jae-Woo Kwon, MD, PhD , So-Young Park, MD, PhD , Sujeong Kim, MD, PhD , Gyu Young Hur, MD, PhD , Byung Keun Kim, MD, PhD , Young-Hee Nam, MD, PhD , Min-Suk Yang, MD, PhD , Mi-Yeong Kim, MD, PhD , Sae-Hoon Kim, MD, PhD , Byung-Jae Lee, MD, PhD , Taehoon Lee, MD, PhD , So Young Park, MD, PhD , Min-Hye Kim, MD, PhD , Young-Joo Cho, MD, PhD , Tae-Bum Kim, MD, PhD","doi":"10.1016/j.waojou.2024.101000","DOIUrl":"10.1016/j.waojou.2024.101000","url":null,"abstract":"<div><h3>Background</h3><div>Limited understanding exists regarding the progression trajectory of severe eosinophilic asthma (SEA) patients on type 2 biologics therapies.</div></div><div><h3>Objective</h3><div>We aim to explore distinct longitudinal phenotypes of these patients based on crucial asthma biomarkers.</div></div><div><h3>Methods</h3><div>We enrolled 101 adult patients with SEA. Of these, 51 were treated with anti-IL5/IL5Rα or anti-IL5/IL5RαR antibody, and 50 with anti-IL-4Rα antibody. Multi-trajectory analysis, an extension of univariate group-based trajectory modeling, was used to categorize patients based on their trajectories of forced expiratory volume in 1 s (FEV<sub>1</sub>), blood eosinophil counts (BEC), and fractional exhaled nitric oxide (FeNO) levels at baseline, and after 1, 6, and 12 months of treatment. Associations between trajectory-based clusters and clinical parameters were examined.</div></div><div><h3>Results</h3><div>Among anti-IL5/IL5Rα antibody-treated patients, 2 clusters were identified. The cluster characterized by higher baseline BEC and lower FEV<sub>1</sub> showed a better response, with improvements in FEV<sub>1</sub> and reductions in BEC over time. Among anti-IL-4Rα antibody-treated, 3 clusters were identified. Clusters with moderate BEC and FeNO at baseline demonstrated better improvements in FEV<sub>1</sub> and reductions in FeNO, despite increased BEC during follow-up. Conversely, individuals with extremely low FeNO and high BEC at baseline were more likely to experience poorer progression, demonstrating an increase in FeNO and a reduction in FEV<sub>1</sub>.</div></div><div><h3>Conclusion</h3><div>To optimally monitor treatment response in SEA patients on type 2 biologics, integrating longitudinal biomarker features is essential.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101000"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699929","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}
Pub Date : 2024-11-20DOI: 10.1016/j.waojou.2024.101001
Sakura Sato MD , Noriyuki Yanagida MD, PhD , Ken-ichi Nagakura MD, PhD , Kyohei Takahashi MD, PhD, MPH , Magnus P. Borres MD, PhD , Motohiro Ebisawa MD, PhD
Background
The clinical importance of sensitization to Arachis hypogaea 6 (Ara h 6) in Japanese children remains unelucidated. We aimed to quantitatively evaluate the clinical importance of sensitization to Ara h 6 in managing peanut allergy in Japanese children.
Methods
We retrospectively analyzed the data of children with or without symptoms induced by an oral food challenge or home dosing of up to 3 g of peanuts. The specific immunoglobulin E (sIgE) levels against peanuts, Ara h 2, and Ara h 6 were quantified using an ImmunoCAP assay.
Results
We examined 273 patients aged 4.6–9.8 years (median 6.3); 189 (69%) were male, 187 (68%) had allergies to peanuts, and 43 (16%) had anaphylactic reactions to peanuts. Ara h 6 and Ara h 2 co-sensitization was observed in 224 patients (82%). Ara h 6-sIgE levels were significantly associated with the probability of allergic reactions and anaphylaxis. The 95% probability of allergic reactions to peanuts was obtained at 44.5 kUA/L of Ara h 6-sIgE, but the 95% probability of anaphylaxis could not be calculated. A combination of Ara h 6 and Ara h 2 could not improve diagnostic accuracy for allergic reactions and anaphylaxis to peanuts.
Conclusion
Sensitization to Ara h 6 played an important role in managing peanut allergy in Japanese children, and sIgE levels provided valuable predictive information for allergic reactions to peanuts. However, the measurement of Ara h 6 did not improve the diagnostic accuracy of anaphylaxis, and Ara h 2 alone might be sufficient for clinical evaluation in peanut allergy.
背景日本儿童对Arachis hypogaea 6（Ara h 6）过敏的临床重要性仍未得到阐明。方法我们回顾性分析了通过口服食物挑战或在家中摄入多达 3 克花生而诱发或未诱发症状的儿童的数据。结果我们对 273 名年龄在 4.6-9.8 岁（中位 6.3 岁）的患者进行了检查，其中 189 名（69%）为男性，187 名（68%）对花生过敏，43 名（16%）对花生有过敏反应。224 名患者（82%）出现了 Ara h 6 和 Ara h 2 共敏现象。Ara h 6-sIgE 水平与过敏反应和过敏性休克的概率显著相关。当 Ara h 6-sIgE 为 44.5 kUA/L 时，发生花生过敏反应的概率为 95%，但过敏性休克的 95% 概率无法计算。Ara h 6 和 Ara h 2 的组合不能提高对花生过敏反应和过敏性休克的诊断准确性。然而，Ara h 6 的测量并不能提高过敏性休克的诊断准确性，仅用 Ara h 2 可能就足以对花生过敏进行临床评估。
{"title":"Evaluating clinical importance of sensitization to Ara h 6 quantitively in Japanese children","authors":"Sakura Sato MD , Noriyuki Yanagida MD, PhD , Ken-ichi Nagakura MD, PhD , Kyohei Takahashi MD, PhD, MPH , Magnus P. Borres MD, PhD , Motohiro Ebisawa MD, PhD","doi":"10.1016/j.waojou.2024.101001","DOIUrl":"10.1016/j.waojou.2024.101001","url":null,"abstract":"<div><h3>Background</h3><div>The clinical importance of sensitization to <em>Arachis hypogaea</em> 6 (Ara h 6) in Japanese children remains unelucidated. We aimed to quantitatively evaluate the clinical importance of sensitization to Ara h 6 in managing peanut allergy in Japanese children.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed the data of children with or without symptoms induced by an oral food challenge or home dosing of up to 3 g of peanuts. The specific immunoglobulin E (sIgE) levels against peanuts, Ara h 2, and Ara h 6 were quantified using an ImmunoCAP assay.</div></div><div><h3>Results</h3><div>We examined 273 patients aged 4.6–9.8 years (median 6.3); 189 (69%) were male, 187 (68%) had allergies to peanuts, and 43 (16%) had anaphylactic reactions to peanuts. Ara h 6 and Ara h 2 co-sensitization was observed in 224 patients (82%). Ara h 6-sIgE levels were significantly associated with the probability of allergic reactions and anaphylaxis. The 95% probability of allergic reactions to peanuts was obtained at 44.5 kU<sub>A</sub>/L of Ara h 6-sIgE, but the 95% probability of anaphylaxis could not be calculated. A combination of Ara h 6 and Ara h 2 could not improve diagnostic accuracy for allergic reactions and anaphylaxis to peanuts.</div></div><div><h3>Conclusion</h3><div>Sensitization to Ara h 6 played an important role in managing peanut allergy in Japanese children, and sIgE levels provided valuable predictive information for allergic reactions to peanuts. However, the measurement of Ara h 6 did not improve the diagnostic accuracy of anaphylaxis, and Ara h 2 alone might be sufficient for clinical evaluation in peanut allergy.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101001"},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699935","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}
Pub Date : 2024-11-19DOI: 10.1016/j.waojou.2024.100997
Divya Dwarakanath BSc, MPhil , Andelija Milic BSc, PhD , Paul J. Beggs BSc, PhD , Darren Wraith BCom, GradDipHE, BMath, PhD , Janet M. Davies BSc, PhD
Background
Contemporary airborne pollen records underpin environmental health warnings, yet how pollen monitoring networks are sustained is poorly understood. This study investigated by whom and how pollen monitoring sites across the globe are managed and funded.
Methods
Coordinators listed in the Worldwide Map of Pollen Monitoring Stations were invited to complete a digital questionnaire designed to survey the people and organisations involved, types, and duration of funding sources, as well as uses, purpose, and sharing of pollen information. Quantitative data were analysed by descriptive statistics and open text responses were examined by qualitative thematic analysis.
Results
Eighty-four of 241 (35%) coordinators from 37 countries responded. Universities (42%) and hospitals/health services (29%) were most commonly responsible for monitoring. Most sites involved employees (87%) in pollen monitoring, of whom many were part-time (41%) or casual (11%), as well as students (29%) and volunteers (6%). Pollen monitoring was additional to core duties for over one-third of sites (35%), and 25% reported pollen monitoring was an in-kind contribution. Whilst funding for pollen monitoring was often sourced from government agencies (33%), government research grants (24%), or non-government grants (8%), 92% reported more than 1 funding source, and 99% reported dependence on “partnerships or grants requiring co-contributions”, indicating a complex resourcing structure, of short duration (median 3 years). Common reasons why airborne pollen was monitored included clinical allergy, population environmental health, aerobiology and forecasting. Climate change, research, and social duty were also referenced.
Conclusions
Aerobiological monitoring is currently sustained by complex, insecure, and insufficient resourcing, as well as reliance on volunteerism. There are multiple direct, health-related, and other important uses of aerobiology data, that are aligned to multiple dimensions of sustainability. Evidence from this study can be used to inform the design of strategies to sustain the generation of aerobiology data.
{"title":"A global survey addressing sustainability of pollen monitoring","authors":"Divya Dwarakanath BSc, MPhil , Andelija Milic BSc, PhD , Paul J. Beggs BSc, PhD , Darren Wraith BCom, GradDipHE, BMath, PhD , Janet M. Davies BSc, PhD","doi":"10.1016/j.waojou.2024.100997","DOIUrl":"10.1016/j.waojou.2024.100997","url":null,"abstract":"<div><h3>Background</h3><div>Contemporary airborne pollen records underpin environmental health warnings, yet how pollen monitoring networks are sustained is poorly understood. This study investigated by whom and how pollen monitoring sites across the globe are managed and funded.</div></div><div><h3>Methods</h3><div>Coordinators listed in the Worldwide Map of Pollen Monitoring Stations were invited to complete a digital questionnaire designed to survey the people and organisations involved, types, and duration of funding sources, as well as uses, purpose, and sharing of pollen information. Quantitative data were analysed by descriptive statistics and open text responses were examined by qualitative thematic analysis.</div></div><div><h3>Results</h3><div>Eighty-four of 241 (35%) coordinators from 37 countries responded. Universities (42%) and hospitals/health services (29%) were most commonly responsible for monitoring. Most sites involved employees (87%) in pollen monitoring, of whom many were part-time (41%) or casual (11%), as well as students (29%) and volunteers (6%). Pollen monitoring was additional to core duties for over one-third of sites (35%), and 25% reported pollen monitoring was an in-kind contribution. Whilst funding for pollen monitoring was often sourced from government agencies (33%), government research grants (24%), or non-government grants (8%), 92% reported more than 1 funding source, and 99% reported dependence on “partnerships or grants requiring co-contributions”, indicating a complex resourcing structure, of short duration (median 3 years). Common reasons why airborne pollen was monitored included clinical allergy, population environmental health, aerobiology and forecasting. Climate change, research, and social duty were also referenced.</div></div><div><h3>Conclusions</h3><div>Aerobiological monitoring is currently sustained by complex, insecure, and insufficient resourcing, as well as reliance on volunteerism. There are multiple direct, health-related, and other important uses of aerobiology data, that are aligned to multiple dimensions of sustainability. Evidence from this study can be used to inform the design of strategies to sustain the generation of aerobiology data.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100997"},"PeriodicalIF":3.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699933","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}
Pub Date : 2024-11-14DOI: 10.1016/j.waojou.2024.100989
Maya Deva MBBS , Merryn J. Netting PhD , Jemma Weidinger MN, NP , Roland Brand FACD , Richard KS. Loh FRACP , Sandra L. Vale PhD
Atopic dermatitis (AD) is a chronic disease that is increasing in prevalence, particularly in children and people with skin of colour. Current management involves topical treatments, phototherapy and immunosuppressants, as well as newer therapies like dupilumab. Health professionals should also be aware of the specific management considerations for AD in people with skin of colour. This systematic review was conducted to examine global guidelines for the management of AD in children, compare management recommendations, examine specific recommendations for children with skin of colour, and assess the quality of the guidelines.
The databases Medline, Embase, CINAHL, Scopus, Guidelines International Network, and Emcare Nursing and Allied Health were searched to identify guidelines or articles relating to the management of AD in children from 1990 to 2023. A grey literature search was also undertaken. The recommendations from the guidelines were extracted and compared, and the quality of the guidelines was assessed using the Appraisal Guidelines for Research and Evaluation (AGREE) II tool.
A total of 1644 articles were identified from the initial search. Title and abstract screening, full text screening, and reference checking yielded 28 guidelines for the final appraisal and data extraction. The main variations in management recommendations were the timing of emollients, bleach baths, bath additives, oral antihistamines, and the age cut-offs for topical calcineurin inhibitors. Many guidelines were not updated to reflect newer therapies like dupilumab and topical phosphodiesterase-4 (PDE4) inhibitors. There were minimal recommendations regarding management of skin of colour. Only 12/28 guidelines met the satisfactory cut-off score for the AGREE II appraisal, largely due to a lack of well-documented methodology.
This review showed that the recommendations for AD management in skin of colour were consistently lacking. Despite generally consistent management strategies over the last 5 years, less than half of the guidelines met high-quality criteria, emphasising the importance of using tools like AGREE II in future guideline development.
特应性皮炎（AD）是一种慢性疾病，发病率越来越高，尤其是在儿童和有色人种中。目前的治疗方法包括局部治疗、光疗、免疫抑制剂以及杜比单抗等新疗法。医疗专业人员还应了解有色人种 AD 的特殊管理注意事项。本系统性综述旨在研究全球儿童注意力缺失症管理指南，比较管理建议，研究针对有色人种儿童的具体建议，并评估指南的质量。我们检索了Medline、Embase、CINAHL、Scopus、Guidelines International Network和Emcare Nursing and Allied Health等数据库，以确定1990年至2023年与儿童注意力缺失症管理相关的指南或文章。此外还进行了灰色文献检索。对指南中的建议进行了提取和比较，并使用研究与评价评估指南（AGREE）II工具对指南的质量进行了评估。通过标题和摘要筛选、全文筛选以及参考文献核对，最终对 28 篇指南进行了评估和数据提取。管理建议的主要差异在于使用润肤剂、漂白浴、沐浴添加剂、口服抗组胺药的时机，以及使用局部降钙素抑制剂的年龄界限。许多指南没有更新以反映新的疗法，如杜匹单抗和外用磷酸二酯酶-4（PDE4）抑制剂。有关有色皮肤管理的建议极少。只有 12/28 份指南达到了 AGREE II 评估的满意临界值，这主要是由于缺乏有据可查的方法。尽管过去 5 年中的管理策略基本一致，但只有不到一半的指南符合高质量标准，这强调了在未来指南制定过程中使用 AGREE II 等工具的重要性。
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Pub Date : 2024-11-14DOI: 10.1016/j.waojou.2024.100986
Rundong Qin MD , Wanyi Fu Ph.D , Renbin Huang MD , Mo Xian MD, Yubiao Guo MD, Li He MD, Xu Shi MD, Jing Li MD
Background
While allergen-specific immunotherapy (AIT) is acknowledged as an effective treatment, its efficacy varies, and consensus on predictive indicators for AIT responders remains elusive.
Objective
This study aimed to identify alternative parameters for predicting AIT responders based on clinical data collected in daily practice.
Method
We conducted a retrospective analysis of patients with house-dust-mite-driven asthma and/or rhinitis who completed 3 years of subcutaneous AIT (3y-AIT). We assessed the efficacy of AIT using the estimated daily symptom and medication score (edSMS) during different treatment periods, including up-dosing, maintenance I, II, and III phases. These scores were derived from detailed records of symptoms and medication use for AIT injections. A responder was defined as an individual with a reduction in edSMS of at least 30% from up-dosing to maintenance III phase (ΔedSMSU-M3).
Results
A cohort of 133 patients was analyzed, revealing a significant overall improvement in the disease condition after 3y-AIT. Responders demonstrated lower rates of polysensitization, daily tobacco smoke exposure, and milder pretreatment disease severity compared to non-responders (p = 0.003, p = 0.001, and p = 0.019, respectively). We observed 8 clinical response patterns among included subjects, but only a small group of patients (16/133, 12.03%) demonstrated consistent improvement throughout the 3y-AIT. Serum total immunoglobulin E (tIgE), specific immunoglobulin E (sIgE), sIgE/tIgE ratios, and edSMS during the up-dosing phase failed to differentiate the clinical response patterns or correlate with 3y-AIT efficacy. Notably, the reduction in edSMS from up-dosing phase to maintenance I phase (ΔedSMSU-M1) significantly associated with the 3y-AIT outcome (r = 0.443, p < 0.001). Receiver-operating characteristic curves indicated that ΔedSMSU-M1, with a cut-off of 18.40%, effectively predicted responders (AUC: 0.75, sensitivity: 76.20%, specificity: 76.70%).
Conclusion
The individualized clinical responses to AIT may pose challenges in identifying predictors for treatment efficacy. Nonetheless, despite this complexity, our study highlights that the effectiveness observed in the early maintenance phase serves as a suitable predictor of 3y-AIT outcomes.
背景虽然过敏原特异性免疫疗法（AIT）被公认为是一种有效的治疗方法，但其疗效却参差不齐，而且对 AIT 反应者的预测指标仍未达成共识。方法我们对完成了 3 年皮下 AIT（3y-AIT）治疗的由屋尘螨引起的哮喘和/或鼻炎患者进行了回顾性分析。在不同的治疗阶段，包括加量、维持 I、II 和 III 阶段，我们使用每日症状和用药估计评分（edSMS）来评估 AIT 的疗效。这些评分来自 AIT 注射时的症状和用药详细记录。结果对 133 例患者进行了分析，结果显示，经过 3 年的 AIT 治疗后，患者的总体病情得到了显著改善。与非应答者相比，应答者的多敏化率、每日烟草烟雾暴露率和治疗前疾病严重程度较轻（分别为 p = 0.003、p = 0.001 和 p = 0.019）。在纳入的受试者中，我们观察到 8 种临床反应模式，但只有一小部分患者（16/133，12.03%）在 3 年的 AIT 中表现出持续的改善。血清总免疫球蛋白 E (tIgE)、特异性免疫球蛋白 E (sIgE)、sIgE/tIgE 比率和加药阶段的 edSMS 未能区分临床反应模式或与 3 年的 AIT 疗效相关。值得注意的是，从加量给药阶段到维持 I 阶段，edSMS 的降低（ΔedSMSU-M1）与 3y-AIT 的结果显著相关（r = 0.443，p < 0.001）。接收者工作特征曲线显示，ΔedSMSU-M1 的临界值为 18.40%，可有效预测应答者（AUC：0.75，灵敏度：76.20%，特异性：76.70%）。尽管如此，尽管存在这种复杂性，我们的研究强调，在早期维持阶段观察到的疗效是预测 AIT 3 年疗效的合适指标。
{"title":"Predicting allergen immunotherapy efficacy based on early maintenance phase response in routine clinical practice","authors":"Rundong Qin MD , Wanyi Fu Ph.D , Renbin Huang MD , Mo Xian MD, Yubiao Guo MD, Li He MD, Xu Shi MD, Jing Li MD","doi":"10.1016/j.waojou.2024.100986","DOIUrl":"10.1016/j.waojou.2024.100986","url":null,"abstract":"<div><h3>Background</h3><div>While allergen-specific immunotherapy (AIT) is acknowledged as an effective treatment, its efficacy varies, and consensus on predictive indicators for AIT responders remains elusive.</div></div><div><h3>Objective</h3><div>This study aimed to identify alternative parameters for predicting AIT responders based on clinical data collected in daily practice.</div></div><div><h3>Method</h3><div>We conducted a retrospective analysis of patients with house-dust-mite-driven asthma and/or rhinitis who completed 3 years of subcutaneous AIT (3y-AIT). We assessed the efficacy of AIT using the estimated daily symptom and medication score (edSMS) during different treatment periods, including up-dosing, maintenance I, II, and III phases. These scores were derived from detailed records of symptoms and medication use for AIT injections. A responder was defined as an individual with a reduction in edSMS of at least 30% from up-dosing to maintenance III phase (ΔedSMS<sub>U-M3</sub>).</div></div><div><h3>Results</h3><div>A cohort of 133 patients was analyzed, revealing a significant overall improvement in the disease condition after 3y-AIT. Responders demonstrated lower rates of polysensitization, daily tobacco smoke exposure, and milder pretreatment disease severity compared to non-responders (p = 0.003, p = 0.001, and p = 0.019, respectively). We observed 8 clinical response patterns among included subjects, but only a small group of patients (16/133, 12.03%) demonstrated consistent improvement throughout the 3y-AIT. Serum total immunoglobulin E (tIgE), specific immunoglobulin E (sIgE), sIgE/tIgE ratios, and edSMS during the up-dosing phase failed to differentiate the clinical response patterns or correlate with 3y-AIT efficacy. Notably, the reduction in edSMS from up-dosing phase to maintenance I phase (ΔedSMS<sub>U-M1</sub>) significantly associated with the 3y-AIT outcome (r = 0.443, p < 0.001). Receiver-operating characteristic curves indicated that ΔedSMS<sub>U-M1</sub>, with a cut-off of 18.40%, effectively predicted responders (AUC: 0.75, sensitivity: 76.20%, specificity: 76.70%).</div></div><div><h3>Conclusion</h3><div>The individualized clinical responses to AIT may pose challenges in identifying predictors for treatment efficacy. Nonetheless, despite this complexity, our study highlights that the effectiveness observed in the early maintenance phase serves as a suitable predictor of 3y-AIT outcomes.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100986"},"PeriodicalIF":3.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142662831","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}
Pub Date : 2024-11-01DOI: 10.1016/j.waojou.2024.100992
Pedro Giavina-Bianchi MD, PhD , Mara Giavina-Bianchi MD, PhD , Raquel de Oliveira Martins , Maria Cristina Fortunato PharmD , Ana Claudia Guersoni MD, PhD
<div><h3>Introduction</h3><div>Hereditary angioedema (HAE) is a rare genetic disease characterized by recurrent, potentially life-threatening angioedema episodes. Despite its severity, including the risk of asphyxiation, HAE often remains underdiagnosed. The disease significantly impacts patient quality of life (QoL), leading to anxiety, depression, and avoidance behaviors due to the unpredictable nature of attacks. Understanding the perspectives of patients is crucial for identifying unmet needs in managing this complex condition.</div></div><div><h3>Objective</h3><div>This study aimed to gather real-world insights from Brazilian patients with C1 inhibitor deficiency HAE to identify their unmet needs and assess their perceptions of the effectiveness of current care in preventing and treating HAE attacks.</div></div><div><h3>Methods</h3><div>A cross-sectional study utilized a SurveyMonkey questionnaire distributed to HAE patients through ABRANGHE via email. Participants provided informed consent, and their responses were anonymous. The questionnaire, developed with input from experts and patients, covered aspects of HAE diagnosis, treatment experiences, and QoL assessments.</div></div><div><h3>Results</h3><div>The survey included 178 HAE patients, predominantly female (81%), aged 30–50 years (58%), and college-educated (62%). The most common HAE defect was C1–INH deficiency (53%), followed by HAE-nC1INH (23%), with nearly a quarter unaware of their specific defect. Diagnosis delays were prevalent, with a significant number reporting 13–50 attacks annually (33%) and 15% experiencing more than 50 attacks per year. Laryngeal involvement was reported by 26% of respondents. Most patients (69%) attended regular follow-ups, with 72% on prophylactic treatment and 67% managing acute attacks. The most used acute treatment was Icatibant (49%), followed by pdC1INH (24%). However, confusion regarding medication use persisted, with 45% incorrectly believing that oral medications could effectively treat attacks. Key unmet needs identified included improved access to emergency rooms during attacks (73%), better availability of prophylactic treatment (69%), and enhanced access to specialized care (63%). Patients also emphasized the need for psychological support, increased awareness of HAE, and educational initiatives for patients and healthcare providers.</div></div><div><h3>Discussion</h3><div>This study highlighted significant challenges in HAE management among Brazilian patients, particularly concerning delayed diagnosis, misconceptions about treatment, and inadequate access to specialized care and prophylactic treatments. The high frequency of emergency room visits underscores the difficulties in managing the disease. The substantial burden of HAE on QoL emphasizes the urgent need for improved physician education, streamlined diagnostic processes, and equitable access to effective medications and specialized care facilities<strong>.</strong> Addressing these
导言遗传性血管性水肿（HAE）是一种罕见的遗传性疾病，其特征是反复发作、可能危及生命的血管性水肿。尽管HAE病情严重，有窒息的危险，但往往诊断不足。这种疾病严重影响患者的生活质量（QoL），由于发作的不可预测性，导致焦虑、抑郁和逃避行为。本研究旨在收集巴西 C1 抑制剂缺乏型 HAE 患者的真实想法，以确定他们未得到满足的需求，并评估他们对目前预防和治疗 HAE 发作的护理效果的看法。方法横断面研究采用 SurveyMonkey 问卷调查法，通过 ABRANGHE 以电子邮件的形式向 HAE 患者发放问卷。参与者在知情的情况下表示同意，他们的回答是匿名的。调查问卷由专家和患者共同参与制定，内容包括 HAE 诊断、治疗经验和 QoL 评估。最常见的 HAE 缺陷是 C1-INH 缺乏（53%），其次是 HAE-nC1INH（23%），近四分之一的患者不知道自己的具体缺陷。诊断延迟的情况很普遍，有相当多的患者报告每年发作 13-50 次（33%），15% 的患者每年发作 50 次以上。26%的受访者称喉部受累。大多数患者（69%）接受定期随访，72%接受预防性治疗，67%接受急性发作治疗。使用最多的急性治疗药物是伊卡替班（49%），其次是 pdC1INH（24%）。然而，在药物使用方面仍然存在困惑，45%的人错误地认为口服药物可以有效治疗疾病发作。未满足的主要需求包括：改善发作时急诊室的就诊条件（73%）、更好地提供预防性治疗（69%）和更多地获得专业护理（63%）。患者还强调需要心理支持、提高对 HAE 的认识，以及对患者和医疗服务提供者开展教育活动。 讨论这项研究强调了巴西患者在 HAE 管理方面面临的重大挑战，尤其是在延迟诊断、对治疗的误解以及无法获得足够的专业护理和预防性治疗等方面。急诊室就诊的频率很高，这凸显了疾病管理的困难。HAE 对 QoL 造成的巨大负担凸显了改善医生教育、简化诊断流程以及公平获得有效药物和专业护理设施的迫切需要。弥补这些不足对于更好地支持 HAE 患者、提高诊断及时性、增强治疗效果以及最终提高 HAE 患者的整体生活质量至关重要。
{"title":"Unmet needs in the management of hereditary angioedema from the perspective of Brazilian patients","authors":"Pedro Giavina-Bianchi MD, PhD , Mara Giavina-Bianchi MD, PhD , Raquel de Oliveira Martins , Maria Cristina Fortunato PharmD , Ana Claudia Guersoni MD, PhD","doi":"10.1016/j.waojou.2024.100992","DOIUrl":"10.1016/j.waojou.2024.100992","url":null,"abstract":"<div><h3>Introduction</h3><div>Hereditary angioedema (HAE) is a rare genetic disease characterized by recurrent, potentially life-threatening angioedema episodes. Despite its severity, including the risk of asphyxiation, HAE often remains underdiagnosed. The disease significantly impacts patient quality of life (QoL), leading to anxiety, depression, and avoidance behaviors due to the unpredictable nature of attacks. Understanding the perspectives of patients is crucial for identifying unmet needs in managing this complex condition.</div></div><div><h3>Objective</h3><div>This study aimed to gather real-world insights from Brazilian patients with C1 inhibitor deficiency HAE to identify their unmet needs and assess their perceptions of the effectiveness of current care in preventing and treating HAE attacks.</div></div><div><h3>Methods</h3><div>A cross-sectional study utilized a SurveyMonkey questionnaire distributed to HAE patients through ABRANGHE via email. Participants provided informed consent, and their responses were anonymous. The questionnaire, developed with input from experts and patients, covered aspects of HAE diagnosis, treatment experiences, and QoL assessments.</div></div><div><h3>Results</h3><div>The survey included 178 HAE patients, predominantly female (81%), aged 30–50 years (58%), and college-educated (62%). The most common HAE defect was C1–INH deficiency (53%), followed by HAE-nC1INH (23%), with nearly a quarter unaware of their specific defect. Diagnosis delays were prevalent, with a significant number reporting 13–50 attacks annually (33%) and 15% experiencing more than 50 attacks per year. Laryngeal involvement was reported by 26% of respondents. Most patients (69%) attended regular follow-ups, with 72% on prophylactic treatment and 67% managing acute attacks. The most used acute treatment was Icatibant (49%), followed by pdC1INH (24%). However, confusion regarding medication use persisted, with 45% incorrectly believing that oral medications could effectively treat attacks. Key unmet needs identified included improved access to emergency rooms during attacks (73%), better availability of prophylactic treatment (69%), and enhanced access to specialized care (63%). Patients also emphasized the need for psychological support, increased awareness of HAE, and educational initiatives for patients and healthcare providers.</div></div><div><h3>Discussion</h3><div>This study highlighted significant challenges in HAE management among Brazilian patients, particularly concerning delayed diagnosis, misconceptions about treatment, and inadequate access to specialized care and prophylactic treatments. The high frequency of emergency room visits underscores the difficulties in managing the disease. The substantial burden of HAE on QoL emphasizes the urgent need for improved physician education, streamlined diagnostic processes, and equitable access to effective medications and specialized care facilities<strong>.</strong> Addressing these","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 11","pages":"Article 100992"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654793","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}
Pub Date : 2024-11-01DOI: 10.1016/j.waojou.2024.100980
Le Li MD , Nan Huang MD , Wenjing Li MD , Yaqi Yang MD , Dongxia Ma MD , Hao Chen MD, PhD , Rongfei Zhu MD, PhD
Background
The incidence of a disease can help health professionals to identify risk factors and health-care policymakers to develop corresponding policies. The realization of both purposes depends on comprehensive studies, especially studies done on a large scale. However, comprehensive studies on the incidence of anaphylaxis among inpatients in China are still notably scarce. Hence we aim to explore the incidence and clinical characteristics of anaphylaxis among inpatients over a span of 21 years in Wuhan, China.
Methods
We retrieved data on anaphylaxis cases from the Data Platform Application Portal (DPAP) across 3 medical centers of Tongji Hospital, Wuhan, China from January 1, 2003, to December 31, 2023.
Results
The data encompassed a total of 362 anaphylaxis patients from 2,139,272 inpatients. Among them 204 (56.4%) were male, and the median age was 45 years old. Over the past 2 decades, the incidence rate of anaphylaxis at Tongji Hospital was 16.92 per 100,000 individuals. After adjusting for gender and age, the annual standardized incidence rate was 234.53 per 100,000 individuals. The incidence rate of anaphylaxis among the inpatients revealed a relatively stable but slowly rising trend over the 21-year observation period. As for the triggers of anaphylaxis, drugs were responsible for 73.6% of triggers, with antibiotics representing the highest proportion of these cases (38.4%). Drug triggers also showed age-specific features: chemotherapy (17.9%) had the highest proportions among children aged 0–3 years; blood products were more prevalent in school-age children. 13.5% of the cases had an unknown cause. In anaphylaxis cases, despite that only 36.0% received epinephrine treatment, the application of epinephrine still showed an ascending trend. Moreover, the mortality rate for anaphylaxis was relatively low (1.6%), displaying a consistent downward trend.
Conclusion
Our study provides insights into the incidence of anaphylaxis among inpatients in Wuhan over a 21-year period. Drugs are the most common triggers for anaphylaxis, and the use of epinephrine in anaphylaxis management is far from optimal.
{"title":"Incidence and trends of anaphylaxis among inpatients from 2003 to 2023 in Wuhan, China: A multicenter retrospective study","authors":"Le Li MD , Nan Huang MD , Wenjing Li MD , Yaqi Yang MD , Dongxia Ma MD , Hao Chen MD, PhD , Rongfei Zhu MD, PhD","doi":"10.1016/j.waojou.2024.100980","DOIUrl":"10.1016/j.waojou.2024.100980","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of a disease can help health professionals to identify risk factors and health-care policymakers to develop corresponding policies. The realization of both purposes depends on comprehensive studies, especially studies done on a large scale. However, comprehensive studies on the incidence of anaphylaxis among inpatients in China are still notably scarce. Hence we aim to explore the incidence and clinical characteristics of anaphylaxis among inpatients over a span of 21 years in Wuhan, China.</div></div><div><h3>Methods</h3><div>We retrieved data on anaphylaxis cases from the Data Platform Application Portal (DPAP) across 3 medical centers of Tongji Hospital, Wuhan, China from January 1, 2003, to December 31, 2023.</div></div><div><h3>Results</h3><div>The data encompassed a total of 362 anaphylaxis patients from 2,139,272 inpatients. Among them 204 (56.4%) were male, and the median age was 45 years old. Over the past 2 decades, the incidence rate of anaphylaxis at Tongji Hospital was 16.92 per 100,000 individuals. After adjusting for gender and age, the annual standardized incidence rate was 234.53 per 100,000 individuals. The incidence rate of anaphylaxis among the inpatients revealed a relatively stable but slowly rising trend over the 21-year observation period. As for the triggers of anaphylaxis, drugs were responsible for 73.6% of triggers, with antibiotics representing the highest proportion of these cases (38.4%). Drug triggers also showed age-specific features: chemotherapy (17.9%) had the highest proportions among children aged 0–3 years; blood products were more prevalent in school-age children. 13.5% of the cases had an unknown cause. In anaphylaxis cases, despite that only 36.0% received epinephrine treatment, the application of epinephrine still showed an ascending trend. Moreover, the mortality rate for anaphylaxis was relatively low (1.6%), displaying a consistent downward trend.</div></div><div><h3>Conclusion</h3><div>Our study provides insights into the incidence of anaphylaxis among inpatients in Wuhan over a 21-year period. Drugs are the most common triggers for anaphylaxis, and the use of epinephrine in anaphylaxis management is far from optimal.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 11","pages":"Article 100980"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555669","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}
Pub Date : 2024-11-01DOI: 10.1016/j.waojou.2024.100991
Su Ji Kim MD , Youn Joo Choi MD , Man Yong Han MD, PhD , Il Tae Hwang MD, PhD , Hey-Sung Baek MD, PhD
Background
Periostin and human chitinase-3-like protein 1 (YKL-40) have been suggested to be involved in the development of airway fibrosis and remodeling. This study aimed to investigate the relationship between serum periostin levels and airway hyperresponsiveness (AHR) and between serum YKL-40 levels and AHR in children with asthma, comparing periostin as a marker for Th2 inflammation and atopy with YKL-40.
Methods
The study involved children aged 6–15 years, comprising 75 with asthma and 29 healthy controls. We measured serum periostin and YKL-40 levels and performed exercise bronchial provocation tests, methacholine challenge tests, spirometry, and FeNO measurements.
Results
Compared to the healthy controls, asthmatic children exhibited significantly elevated levels of periostin (86.7 [71.0–104.0] vs 68.3 [56.0–82.0] ng/mL; P = 0.006) and YKL-40 (29.0 [15.0–39.5] vs 27.7 [14.0–34.1] ng/mL; P = 0.034). The subgroup analysis revealed that periostin levels were significantly higher in the atopic asthma group than in the healthy controls (P = 0.003), but not in the non-atopic asthma group. YKL-40 levels were elevated in both the atopic and non-atopic asthma groups compared to healthy controls (P = 0.012 and P = 0.001, respectively). Serum periostin levels were significantly correlated with the postexerceise maximum percentage decrease in forced expiratory volume (FEV1), as well as with fractional exhaled nitric oxide (FeNO) and blood eosinophil counts, but showed no significant correlation with overall lung function. Conversely, serum YKL-40 levels were significantly linked to the Z score of FEV1 and AHR to methacholine but not with AHR to exercise or FeNO or blood eosinophil count.
Conclusions
Periostin is linked to atopic asthma and correlates with exercise-induced bronchoconstriction, FeNO, and eosinophil counts, highlighting its role in Th2 inflammation. YKL-40 is a general asthma marker, indicating airway remodeling. These findings suggest that targeting these markers can improve personalized treatment strategies for pediatric asthma.
{"title":"Evaluating serum periostin and YKL-40 as biomarkers for airway remodeling and hyperresponsiveness in pediatric asthma","authors":"Su Ji Kim MD , Youn Joo Choi MD , Man Yong Han MD, PhD , Il Tae Hwang MD, PhD , Hey-Sung Baek MD, PhD","doi":"10.1016/j.waojou.2024.100991","DOIUrl":"10.1016/j.waojou.2024.100991","url":null,"abstract":"<div><h3>Background</h3><div>Periostin and human chitinase-3-like protein 1 (YKL-40) have been suggested to be involved in the development of airway fibrosis and remodeling. This study aimed to investigate the relationship between serum periostin levels and airway hyperresponsiveness (AHR) and between serum YKL-40 levels and AHR in children with asthma, comparing periostin as a marker for Th2 inflammation and atopy with YKL-40.</div></div><div><h3>Methods</h3><div>The study involved children aged 6–15 years, comprising 75 with asthma and 29 healthy controls. We measured serum periostin and YKL-40 levels and performed exercise bronchial provocation tests, methacholine challenge tests, spirometry, and FeNO measurements.</div></div><div><h3>Results</h3><div>Compared to the healthy controls, asthmatic children exhibited significantly elevated levels of periostin (86.7 [71.0–104.0] vs 68.3 [56.0–82.0] ng/mL; P = 0.006) and YKL-40 (29.0 [15.0–39.5] vs 27.7 [14.0–34.1] ng/mL; P = 0.034). The subgroup analysis revealed that periostin levels were significantly higher in the atopic asthma group than in the healthy controls (P = 0.003), but not in the non-atopic asthma group. YKL-40 levels were elevated in both the atopic and non-atopic asthma groups compared to healthy controls (P = 0.012 and P = 0.001, respectively). Serum periostin levels were significantly correlated with the postexerceise maximum percentage decrease in forced expiratory volume (FEV<sub>1</sub>), as well as with fractional exhaled nitric oxide (FeNO) and blood eosinophil counts, but showed no significant correlation with overall lung function. Conversely, serum YKL-40 levels were significantly linked to the Z score of FEV<sub>1</sub> and AHR to methacholine but not with AHR to exercise or FeNO or blood eosinophil count.</div></div><div><h3>Conclusions</h3><div>Periostin is linked to atopic asthma and correlates with exercise-induced bronchoconstriction, FeNO, and eosinophil counts, highlighting its role in Th2 inflammation. YKL-40 is a general asthma marker, indicating airway remodeling. These findings suggest that targeting these markers can improve personalized treatment strategies for pediatric asthma.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 11","pages":"Article 100991"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555670","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}
Pub Date : 2024-11-01DOI: 10.1016/j.waojou.2024.100988
Peter N. Le Souëf MD , Yuichi Adachi MD, PhD , Eleni Anastasiou MD , Ignacio J. Ansotegui MD, PhD , Héctor A. Badellino MD, PhD , Tina Banzon MD , Cesar Pozo Beltrán MD , Gennaro D'Amato MD , Zeinab A. El-Sayed MD, PhD , Rene Maximiliano Gómez PhD , Elham Hossny MD, PhD , Ömer Kalayci MD , Mário Morais-Almeida MD, PhD , Antonio Nieto-Garcia MD, PhD , David B. Peden MD, MS , Wanda Phipatanakul MD , Jiu-Yao Wang MD, DPhil , I-Jen Wan MD, PhD , Gary Wong MD , Paraskevi Xepapadaki MD , Nikolaos G. Papadopoulos MD, PhD
The twenty-first century has seen a fundamental shift in disease epidemiology with anthropogenic environmental change emerging as the likely dominant factor affecting the distribution and severity of current and future human disease. This is especially true of allergic diseases and asthma with their intimate relationship with the natural environment. Climate change-related variables including increased ambient temperature, heat waves, extreme weather events, air pollution, and rainfall distribution, all can directly affect asthma in children, but each of these variables also indirectly affects asthma via alterations in pollen production and release, outdoor allergen exposure or the microbiome. Air pollution, with its many and varied respiratory consequences, is likely to have the greatest effect, as it has increased globally due to rapid increases in fossil fuel combustion, global population, crowding, and megacities, as well as forest burning and trees succumbing to an increasingly hostile environment. Human activities have also caused substantial deterioration of the global microbiome with reductions in biodiversity for molds, bacteria, and viruses. Reduced microbiome diversity has, in turn, been associated with increases in Th2 allergic responses and allergic disease. The collective effect of these changes has already shifted allergy and asthma disease patterns. Given that changes in climate have been relatively small to date, the unavoidable, much greater shifts in climate in the future are concerning. Determining the relative scale of the direct versus indirect effects of climate change variables is needed if effective avoidance and adaptive measures are to be implemented. This would also require much more basic, epidemiological, and clinical research to understand the causal mechanisms, the most relevant climate factors involved, the regions most affected and, most importantly, effective and actionable adaptation measures. We suggest that allergy and respiratory health workers should follow current guidance to reduce present risks related to climate change and watch for new recommendations to reduce future risks. Since the respiratory system is the one most affected by climate change, they also need to call for more research in this area and show strong leadership in advocating for urgent action to protect children by reducing or reversing factors that have led to our deteriorating climate.
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