There is accumulating evidence that allergy is a risk factor for keratoconus. Nonetheless the association between allergic disease and keratoconus remains controversial. We performed a two-sample Mendelian randomization (MR) study to determine the putative causal association of 4 allergic diseases (allergic conjunctivitis, allergic asthma, allergic rhinitis and atopic dermatitis) with keratoconus.
Methods
Summary statistics were obtained from genome-wide association studies (GWAS) of allergic conjunctivitis (AC) (20,958 cases and 356,319 controls), allergic asthma (AA) (9631 cases and 210,122 controls), allergic rhinitis (AR) (11,009 cases and 359,149 controls), atopic dermatitis (AD) (13,473 cases and 336,589 controls), keratoconus (KC) (2116 cases and 24,626 controls) and 91 circulating inflammatory cytokines (n = 14,824). Two-sample univariable and multivariable MR analyses were performed. A two-step MR was then applied to determine whether systemic inflammatory cytokines mediated the effect of allergic disease on keratoconus.
Results
The causal odds ratio (OR) estimate of genetically determined KC was 1.66 (95% CI: 1.32–2.08; P < 0.001) for AC, 1.29 (95% CI: 1.10–1.51, P = 0.0014) for AA, 1.39 (95% CI: 1.15–1.68; P < 0.001) for AR and 1.30 (95% CI: 1.17–1.45, P < 0.001) for AD. Multivariable MR indicated a suggestive association between AC and KC after conditioning on other allergic diseases (OR 1.61; 95% CI: 1.10–2.34; P adjusted = 0.054). Two-step MR revealed that the effect was not mediated by systemic inflammatory cytokines.
Conclusions
Our findings provide evidence of a potential causal relationship between AC and KC. The effect of AC on KC may be mediated via other systemic inflammatory cytokines not included in the present study, or by alternative mechanisms. These findings may offer insight for prevention and intervention strategies to lower the risk of KC in patients with AC.
{"title":"Allergic disease and keratoconus: A two-sample univariable and multivariable Mendelian randomization study","authors":"Hanlu Xu , Yajing Wen , Huikang Zheng , Dan Jiang , Wei Chen","doi":"10.1016/j.waojou.2024.100993","DOIUrl":"10.1016/j.waojou.2024.100993","url":null,"abstract":"<div><h3>Background</h3><div>There is accumulating evidence that allergy is a risk factor for keratoconus. Nonetheless the association between allergic disease and keratoconus remains controversial. We performed a two-sample Mendelian randomization (MR) study to determine the putative causal association of 4 allergic diseases (allergic conjunctivitis, allergic asthma, allergic rhinitis and atopic dermatitis) with keratoconus.</div></div><div><h3>Methods</h3><div>Summary statistics were obtained from genome-wide association studies (GWAS) of allergic conjunctivitis (AC) (20,958 cases and 356,319 controls), allergic asthma (AA) (9631 cases and 210,122 controls), allergic rhinitis (AR) (11,009 cases and 359,149 controls), atopic dermatitis (AD) (13,473 cases and 336,589 controls), keratoconus (KC) (2116 cases and 24,626 controls) and 91 circulating inflammatory cytokines (n = 14,824). Two-sample univariable and multivariable MR analyses were performed. A two-step MR was then applied to determine whether systemic inflammatory cytokines mediated the effect of allergic disease on keratoconus.</div></div><div><h3>Results</h3><div>The causal odds ratio (OR) estimate of genetically determined KC was 1.66 (95% CI: 1.32–2.08; P < 0.001) for AC, 1.29 (95% CI: 1.10–1.51, P = 0.0014) for AA, 1.39 (95% CI: 1.15–1.68; P < 0.001) for AR and 1.30 (95% CI: 1.17–1.45, P < 0.001) for AD. Multivariable MR indicated a suggestive association between AC and KC after conditioning on other allergic diseases (OR 1.61; 95% CI: 1.10–2.34; P adjusted = 0.054). Two-step MR revealed that the effect was not mediated by systemic inflammatory cytokines.</div></div><div><h3>Conclusions</h3><div>Our findings provide evidence of a potential causal relationship between AC and KC. The effect of AC on KC may be mediated via other systemic inflammatory cytokines not included in the present study, or by alternative mechanisms. These findings may offer insight for prevention and intervention strategies to lower the risk of KC in patients with AC.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100993"},"PeriodicalIF":3.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699927","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 : 2024-11-21DOI: 10.1016/j.waojou.2024.101003
James K.Y. Hooi MBChB , Marshall C.H. Low BPharm , Jonathan C.L. To BPharm , Hugo W.F. Mak MBBS , Mandy M. Choi BPharm , Chris C.P. Tam BPharm , Raymond W.M. Mak MSc , Vincent K.C. Wong MPharm , Timo C.C. Chan MClinPharm , Andrew W.T. Li MClinPharm , Charlie C.Y. Mak MClinPharm , Valerie Chiang MBBS , Gordon K.H. Chu MBBS , Jane C.Y. Wong MBBS , Philip H. Li MD
Background
Mislabelled penicillin allergies are associated with a myriad of adverse outcomes and development of anti-microbial resistance. With the overwhelming need for specialist allergy services, pharmacist initiatives such as the Hong Kong Penicillin Allergy Pharmacist Initiative (HK-PAPI) have been advocated. However, evidence of their effectiveness, safety and impact on health-related quality-of-life (HR-QoL) are lacking.
To assess and compare the effectiveness, safety and improvements on HR-QoL of pharmacists vs allergists in a pilot low-risk penicillin allergy delabelling initiative.
Methods
All adult patients referred for low-risk penicillin allergy were randomized and evaluated by either pharmacists or allergists in a 1:3 ratio. Outcomes and changes in Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) scores were compared.
Results
Of 323 patients referred, 96.3% (311/323) completed penicillin allergy evaluation (pharmacists: 83 [24.3%] vs allergists: 228 [66.7%]). Overall, 93.6% (291/311) were delabelled with no difference between evaluations by pharmacists and allergists (92.8% vs 93.9%, p = 0.729). There were no severe or systemic reactions in either cohort. Patients evaluated by either pharmacists (43.4 [SD:29.1] to 10.5 [SD:5.93], p < 0.001) or allergists (37.2 [SD:22.2] to 29.1 [SD:22.4], p < 0.001) reported improved HR-QoL as reflected by DrHy-Q scores. However, absolute changes in DrHy-Q scores were significantly greater among patients evaluated by pharmacists compared to those by allergists (−24.6 [SD:25.1] vs −9.19 [SD:13.7], p < 0.001).
Conclusions
Evaluations and delabelling by pharmacists (vs allergists) were comparably effective and safe among patients with low-risk penicillin allergy. Moreover, patients evaluated by pharmacists even reported significantly greater improvements in HR-QoL, highlighting the potential of multidisciplinary allergy initiatives.
背景对青霉素过敏与多种不良后果和抗微生物抗药性的产生有关。由于对过敏专科服务的巨大需求，药剂师倡议，如香港青霉素过敏药剂师倡议（HK-PAPI）已被提倡。方法对所有转诊的低风险青霉素过敏成人患者进行随机分组，由药剂师或过敏学家按照 1:3 的比例进行评估。结果在转诊的 323 名患者中，96.3%（311/323）的患者完成了青霉素过敏评估（药剂师：83 [24.3%] vs 过敏症专家：228 [66.7%]）。总体而言，93.6%（291/311）的患者被除名，药剂师和过敏学家的评估结果无差异（92.8% vs 93.9%，p = 0.729）。两组患者均未出现严重或全身性反应。由药剂师（43.4 [SD:29.1] 对 10.5 [SD:5.93], p <0.001）或过敏症专家（37.2 [SD:22.2] 对 29.1 [SD:22.4], p <0.001）评估的患者的 HR-QoL 均有所改善，DrHy-Q 评分反映了这一点。结论 在低风险青霉素过敏症患者中，由药剂师（与过敏症专家）进行评估和脱敏治疗的效果和安全性相当。此外，接受药剂师评估的患者甚至在 HR-QoL 方面有明显改善，这凸显了多学科过敏措施的潜力。
{"title":"Comparing pharmacists versus allergists in low-risk penicillin allergy delabelling: The Hong Kong Penicillin Allergy Pharmacist Initiative (HK-PAPI)","authors":"James K.Y. Hooi MBChB , Marshall C.H. Low BPharm , Jonathan C.L. To BPharm , Hugo W.F. Mak MBBS , Mandy M. Choi BPharm , Chris C.P. Tam BPharm , Raymond W.M. Mak MSc , Vincent K.C. Wong MPharm , Timo C.C. Chan MClinPharm , Andrew W.T. Li MClinPharm , Charlie C.Y. Mak MClinPharm , Valerie Chiang MBBS , Gordon K.H. Chu MBBS , Jane C.Y. Wong MBBS , Philip H. Li MD","doi":"10.1016/j.waojou.2024.101003","DOIUrl":"10.1016/j.waojou.2024.101003","url":null,"abstract":"<div><h3>Background</h3><div>Mislabelled penicillin allergies are associated with a myriad of adverse outcomes and development of anti-microbial resistance. With the overwhelming need for specialist allergy services, pharmacist initiatives such as the Hong Kong Penicillin Allergy Pharmacist Initiative (HK-PAPI) have been advocated. However, evidence of their effectiveness, safety and impact on health-related quality-of-life (HR-QoL) are lacking.</div><div>To assess and compare the effectiveness, safety and improvements on HR-QoL of pharmacists vs allergists in a pilot low-risk penicillin allergy delabelling initiative.</div></div><div><h3>Methods</h3><div>All adult patients referred for low-risk penicillin allergy were randomized and evaluated by either pharmacists or allergists in a 1:3 ratio. Outcomes and changes in Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) scores were compared.</div></div><div><h3>Results</h3><div>Of 323 patients referred, 96.3% (311/323) completed penicillin allergy evaluation (pharmacists: 83 [24.3%] vs allergists: 228 [66.7%]). Overall, 93.6% (291/311) were delabelled with no difference between evaluations by pharmacists and allergists (92.8% vs 93.9%, p = 0.729). There were no severe or systemic reactions in either cohort. Patients evaluated by either pharmacists (43.4 [SD:29.1] to 10.5 [SD:5.93], p < 0.001) or allergists (37.2 [SD:22.2] to 29.1 [SD:22.4], p < 0.001) reported improved HR-QoL as reflected by DrHy-Q scores. However, absolute changes in DrHy-Q scores were significantly greater among patients evaluated by pharmacists compared to those by allergists (−24.6 [SD:25.1] vs −9.19 [SD:13.7], p < 0.001).</div></div><div><h3>Conclusions</h3><div>Evaluations and delabelling by pharmacists (vs allergists) were comparably effective and safe among patients with low-risk penicillin allergy. Moreover, patients evaluated by pharmacists even reported significantly greater improvements in HR-QoL, highlighting the potential of multidisciplinary allergy initiatives.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101003"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699934","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 : 2024-11-21DOI: 10.1016/j.waojou.2024.100994
Tamo Sultan MD , Frederikke Skov MD , Nicklas Brustad MD, PhD , Nilo Vahman MD, PhD , Jakob Stokholm MD, PhD , Klaus Bønnelykke MD, PhD , Ann-Marie Malby Schoos MD, PhD, DMSc , Bo Chawes MD, PhD, DMSc
Background
T2-high asthma is characterized by elevated blood eosinophils (b-eos), and/or fractional exhaled nitric oxide (FeNO), and/or being “allergy-driven”, which is not well-defined.
Objective
To investigate the role of total and specific immunoglobulin E (tIgE/sIgE) for defining and predicting T2-high asthma in childhood as biomarkers of “allergy-driven”.
Methods
We utilized data from the COPSAC2000 (n = 411) and COPSAC2010 (n = 700) mother-child cohorts with repeated measurements of tIgE, sIgE, b-eos and FeNO through childhood. We defined T2-high asthma by elevated b-eos (≥0.3 × 109/L) and/or FeNO (≥20 ppb) and analyzed association with elevated tIgE (age-specific cut-offs) and sIgE (≥0.35 kU/L) using logistic regression at ages 7/10/13/18 years. Further, we analyzed the association between elevated tIgE and sIgE at age 0–4 years and later risk of T2-high asthma using logistic regression and ROC models.
Results
Elevated tIgE was associated with risk of T2-high asthma at all time points, whereas elevated sIgE showed similar results at ages 10/13/18 years. There was no overall model fit preference for a combination of tIgE and sIgE instead of tIgE or sIgE alone using Vuong's Likelihood-Ratio-Test, Akaike or Bayesian Information Criterion. Further, elevated tIgE at age 0–4 years was associated with later risk of T2-high asthma at all time points (AUC = 0.63–0.70, sensitivity = 0.62–0.81, specificity = 0.57–0.78), whereas elevated sIgE at 0–4 years was only associated with T2-high asthma at 18 years (AUC = 0.66, sensitivity = 0.45, specificity = 0.88). There were no significant differences in AUC values between tIgE and sIgE (DeLong's test).
Conclusion
Elevated tIgE and sIgE are equally useful stand-alone biomarkers for defining and predicting risk of T2-high asthma in childhood.
{"title":"Levels of total IgE versus specific IgE during childhood for defining and predicting T2-high asthma","authors":"Tamo Sultan MD , Frederikke Skov MD , Nicklas Brustad MD, PhD , Nilo Vahman MD, PhD , Jakob Stokholm MD, PhD , Klaus Bønnelykke MD, PhD , Ann-Marie Malby Schoos MD, PhD, DMSc , Bo Chawes MD, PhD, DMSc","doi":"10.1016/j.waojou.2024.100994","DOIUrl":"10.1016/j.waojou.2024.100994","url":null,"abstract":"<div><h3>Background</h3><div>T2-high asthma is characterized by elevated blood eosinophils (b-eos), and/or fractional exhaled nitric oxide (FeNO), and/or being “allergy-driven”, which is not well-defined.</div></div><div><h3>Objective</h3><div>To investigate the role of total and specific immunoglobulin E (tIgE/sIgE) for defining and predicting T2-high asthma in childhood as biomarkers of “allergy-driven”.</div></div><div><h3>Methods</h3><div>We utilized data from the COPSAC2000 (n = 411) and COPSAC2010 (n = 700) mother-child cohorts with repeated measurements of tIgE, sIgE, b-eos and FeNO through childhood. We defined T2-high asthma by elevated b-eos (≥0.3 × 10<sup>9</sup>/L) and/or FeNO (≥20 ppb) and analyzed association with elevated tIgE (age-specific cut-offs) and sIgE (≥0.35 kU/L) using logistic regression at ages 7/10/13/18 years. Further, we analyzed the association between elevated tIgE and sIgE at age 0–4 years and later risk of T2-high asthma using logistic regression and ROC models.</div></div><div><h3>Results</h3><div>Elevated tIgE was associated with risk of T2-high asthma at all time points, whereas elevated sIgE showed similar results at ages 10/13/18 years. There was no overall model fit preference for a combination of tIgE and sIgE instead of tIgE or sIgE alone using Vuong's Likelihood-Ratio-Test, Akaike or Bayesian Information Criterion. Further, elevated tIgE at age 0–4 years was associated with later risk of T2-high asthma at all time points (AUC = 0.63–0.70, sensitivity = 0.62–0.81, specificity = 0.57–0.78), whereas elevated sIgE at 0–4 years was only associated with T2-high asthma at 18 years (AUC = 0.66, sensitivity = 0.45, specificity = 0.88). There were no significant differences in AUC values between tIgE and sIgE (DeLong's test).</div></div><div><h3>Conclusion</h3><div>Elevated tIgE and sIgE are equally useful stand-alone biomarkers for defining and predicting risk of T2-high asthma in childhood.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100994"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699930","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 : 2024-11-21DOI: 10.1016/j.waojou.2024.100995
Junhao Tu PhD, MD , Wei Wan PhD, MD , Binxiang Tang MSc , Fan Jiang MSc , Jinyang Wen PhD, MD , Qing Luo PhD, MD , Jing Ye PhD, MD
Background
Allergic diseases, such as asthma and allergic rhinitis, present significant health challenges globally. Elucidating the genetic and epigenetic foundations is crucial for developing effective interventions.
Methods
We performed two-sample Mendelian Randomization (MR) analyses to investigate the associations between smoking behaviors and various allergic diseases, leveraging data from the FinnGen database. Additionally, we examined the relationships of DNA methylation (CpG sites) with allergic diseases, employing mQTLs as epigenetic proxies. Furthermore, we conducted reverse MR analyses on CpG sites that exhibited cross-allergic disease effects.
Results
In our genomic MR analysis, smoking behaviors such as smoking initiation and the number of cigarettes smoked per day were identified to be causally associated with an increased risk of asthma. Additionally, there was suggestive evidence linking smoking initiation to atopic contact dermatitis. Our epigenetic MR analysis found that methylation changes at 46 CpG sites, assessed via mQTLs, were significantly associated with asthma risk. Notably, cg17272563 (PRRT1), cg03689048 (BAT3), cg20069688 (STK19), and cg20513976 (LIME1) were identified with cross-allergic effects. Crucially, reverse MR analysis substantiated these associations.
Conclusions
Our study has highlighted the associations between smoking behaviors and allergic diseases in the genetic and epigenetic landscape, notably asthma. We identified several DNA methylation-related CpG sites, such as cg03689048 (BAT3), cg17272563 (PRRT1), and cg20069688 (STK19), which demonstrate cross-allergic potential and reverse causal relationships.
{"title":"Dissecting the pathogenic effects of smoking in blood DNA methylation on allergic diseases","authors":"Junhao Tu PhD, MD , Wei Wan PhD, MD , Binxiang Tang MSc , Fan Jiang MSc , Jinyang Wen PhD, MD , Qing Luo PhD, MD , Jing Ye PhD, MD","doi":"10.1016/j.waojou.2024.100995","DOIUrl":"10.1016/j.waojou.2024.100995","url":null,"abstract":"<div><h3>Background</h3><div>Allergic diseases, such as asthma and allergic rhinitis, present significant health challenges globally. Elucidating the genetic and epigenetic foundations is crucial for developing effective interventions.</div></div><div><h3>Methods</h3><div>We performed two-sample Mendelian Randomization (MR) analyses to investigate the associations between smoking behaviors and various allergic diseases, leveraging data from the FinnGen database. Additionally, we examined the relationships of DNA methylation (CpG sites) with allergic diseases, employing mQTLs as epigenetic proxies. Furthermore, we conducted reverse MR analyses on CpG sites that exhibited cross-allergic disease effects.</div></div><div><h3>Results</h3><div>In our genomic MR analysis, smoking behaviors such as smoking initiation and the number of cigarettes smoked per day were identified to be causally associated with an increased risk of asthma. Additionally, there was suggestive evidence linking smoking initiation to atopic contact dermatitis. Our epigenetic MR analysis found that methylation changes at 46 CpG sites, assessed via mQTLs, were significantly associated with asthma risk. Notably, cg17272563 (PRRT1), cg03689048 (BAT3), cg20069688 (STK19), and cg20513976 (LIME1) were identified with cross-allergic effects. Crucially, reverse MR analysis substantiated these associations.</div></div><div><h3>Conclusions</h3><div>Our study has highlighted the associations between smoking behaviors and allergic diseases in the genetic and epigenetic landscape, notably asthma. We identified several DNA methylation-related CpG sites, such as cg03689048 (BAT3), cg17272563 (PRRT1), and cg20069688 (STK19), which demonstrate cross-allergic potential and reverse causal relationships.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100995"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699928","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 : 2024-11-21DOI: 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。
{"title":"A systematic review of guidelines for the management of atopic dermatitis in children","authors":"Maya Deva MBBS , Merryn J. Netting PhD , Jemma Weidinger MN, NP , Roland Brand FACD , Richard KS. Loh FRACP , Sandra L. Vale PhD","doi":"10.1016/j.waojou.2024.100989","DOIUrl":"10.1016/j.waojou.2024.100989","url":null,"abstract":"<div><div>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.</div><div>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.</div><div>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.</div><div>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.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100989"},"PeriodicalIF":3.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142662832","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.2024.100986
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。
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