Pub Date : 2025-01-01DOI: 10.1016/j.waojou.2024.101014
Xingling Tan MD , Zhouyouyou Xiao MB , Yao Wen MD , Han Liu MD , Wei Yu MD
Background
Allergic rhinitis (AR) is a common chronic respiratory disease that can lead to the development of various other conditions. Although genetic risk loci associated with AR have been reported, the connections between these loci and AR comorbidities or other diseases remain unclear.
Methods
This study conducted a phenome-wide association study (PheWAS) using known AR risk loci to explore the impact of known AR risk variants on a broad spectrum of phenotypes. Subsequently, linkage disequilibrium score regression (LDSC) and bidirectional two-sample mendelian randomization (TSMR) analyses were used to further analyze the genetic correlation and causal relationships between significant and potentially related phenotypes and AR.
Results
The PheWAS analysis indicated significant associations between asthma, eczema, nasal polyps, hypothyroidism, and AR risk variants. Additionally, potential associations were observed with ulcerative colitis, psoriasis, chalazion, pernicious anemia, glaucoma, multiple sclerosis, arthritis, prostate cancer, varicose veins of lower extremities, and heart attack. LDSC analysis showed that only asthma, eczema, and nasal polyps have significant positive genetic correlations with AR. Furthermore, TSMR analysis revealed causal relationships between AR and asthma, eczema, and nasal polyps.
Conclusion
This study highlights the impact of AR risk loci on a variety of diseases. By revealing new associations and shared genetic pathways, our findings provide valuable insights into the pathophysiology of AR and pave the way for more effective targeted interventions to manage AR and its related diseases.
{"title":"Advancing allergic rhinitis research through phenome-wide association studies: Insights from known genetic loci","authors":"Xingling Tan MD , Zhouyouyou Xiao MB , Yao Wen MD , Han Liu MD , Wei Yu MD","doi":"10.1016/j.waojou.2024.101014","DOIUrl":"10.1016/j.waojou.2024.101014","url":null,"abstract":"<div><h3>Background</h3><div>Allergic rhinitis (AR) is a common chronic respiratory disease that can lead to the development of various other conditions. Although genetic risk loci associated with AR have been reported, the connections between these loci and AR comorbidities or other diseases remain unclear.</div></div><div><h3>Methods</h3><div>This study conducted a phenome-wide association study (PheWAS) using known AR risk loci to explore the impact of known AR risk variants on a broad spectrum of phenotypes. Subsequently, linkage disequilibrium score regression (LDSC) and bidirectional two-sample mendelian randomization (TSMR) analyses were used to further analyze the genetic correlation and causal relationships between significant and potentially related phenotypes and AR.</div></div><div><h3>Results</h3><div>The PheWAS analysis indicated significant associations between asthma, eczema, nasal polyps, hypothyroidism, and AR risk variants. Additionally, potential associations were observed with ulcerative colitis, psoriasis, chalazion, pernicious anemia, glaucoma, multiple sclerosis, arthritis, prostate cancer, varicose veins of lower extremities, and heart attack. LDSC analysis showed that only asthma, eczema, and nasal polyps have significant positive genetic correlations with AR. Furthermore, TSMR analysis revealed causal relationships between AR and asthma, eczema, and nasal polyps.</div></div><div><h3>Conclusion</h3><div>This study highlights the impact of AR risk loci on a variety of diseases. By revealing new associations and shared genetic pathways, our findings provide valuable insights into the pathophysiology of AR and pave the way for more effective targeted interventions to manage AR and its related diseases.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 1","pages":"Article 101014"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980468","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 : 2025-01-01DOI: 10.1016/j.waojou.2024.101021
Jean Bousquet MD , Ludger Klimek MD , Hans-Christian Kuhl PhD , Duc Tung Nguyen MD , Rajesh Kumar Ramalingam MD , G. Walter Canonica MD , William E. Berger MD
Some double-blind, placebo-controlled trials have shown that Azelastine (Aze) high dose (0.15%) was effective in seasonal (SAR) and perennial allergic rhinitis (PAR). However, there was no long-term comparison between Aze 0.15% and intranasal corticosteroids (INCS) on safety and quality of life in perennial allergic rhinitis.
An open-label, active-controlled, parallel-group one-year study comparing mometasone furoate and Aze 0.15% in adults assessed safety over 1 year. Efficacy using the 28-item rhino-conjunctivitis quality of life questionnaire (RQLQ) was a secondary end point.
A total of 703 patients were randomized and 687 (97.7%) were included in the intent-to-treat (ITT) population. The present formulation was shown to be safe with long-term use over 12 months, with a mean duration of exposure of 270.7 days.
Over the one-year period, there was no significant difference for any RQLQ domains between Aze and mometasone furoate (MF) for all evaluations (baseline, 6, 9, and 12 months). This study suggests that Aze 0.15% and MF display a similar improvement of RQLQ ( 2.80 [2.78] for Aze 0.15% vs 2.81 [2.75] for MF).
Clinical trial registry number
NCT00720382.
{"title":"In perennial allergic rhinitis, RQLQ is improved similarly by Azelastine 0.15 and mometasone furoate","authors":"Jean Bousquet MD , Ludger Klimek MD , Hans-Christian Kuhl PhD , Duc Tung Nguyen MD , Rajesh Kumar Ramalingam MD , G. Walter Canonica MD , William E. Berger MD","doi":"10.1016/j.waojou.2024.101021","DOIUrl":"10.1016/j.waojou.2024.101021","url":null,"abstract":"<div><div>Some double-blind, placebo-controlled trials have shown that Azelastine (Aze) high dose (0.15%) was effective in seasonal (SAR) and perennial allergic rhinitis (PAR). However, there was no long-term comparison between Aze 0.15% and intranasal corticosteroids (INCS) on safety and quality of life in perennial allergic rhinitis.</div><div>An open-label, active-controlled, parallel-group one-year study comparing mometasone furoate and Aze 0.15% in adults assessed safety over 1 year. Efficacy using the 28-item rhino-conjunctivitis quality of life questionnaire (RQLQ) was a secondary end point.</div><div>A total of 703 patients were randomized and 687 (97.7%) were included in the intent-to-treat (ITT) population. The present formulation was shown to be safe with long-term use over 12 months, with a mean duration of exposure of 270.7 days.</div><div>Over the one-year period, there was no significant difference for any RQLQ domains between Aze and mometasone furoate (MF) for all evaluations (baseline, 6, 9, and 12 months). This study suggests that Aze 0.15% and MF display a similar improvement of RQLQ ( 2.80 [2.78] for Aze 0.15% vs 2.81 [2.75] for MF).</div></div><div><h3>Clinical trial registry number</h3><div>NCT00720382.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 1","pages":"Article 101021"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069730","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 : 2024-12-01DOI: 10.1016/j.waojou.2024.101011
Dorra Gharbi PhD , Dilys Berman PhD , Frank H. Neumann PhD , Trevor Hill PhD , Siyavuya Sidla BSc , Sarel S. Cillers PhD , Jurgens Staats MD , Nanike Esterhuizen PhD , Linus Ajikah PhD , Moteng E. Moseri MSc , Lynne J. Quick PhD , Erin Hilmer BSc , Andri Van Aardt PhD , Juanette John PhD , Rebecca Garland PhD , Jemma Finch PhD , Werner Hoek MD , Marion Bamford PhD , Riaz Y. Seedat MD , Ahmed I. Manjra MD , Jonny Peter MD, PhD
Background
Ragweed is an invasive, highly allergenic weed predicted to expand its habitat with warming global temperatures. Several Ambrosia species have been identified in South Africa for well over a century; however, its presence remained undetected by allergists and aerobiologists until the development of an extensive aerospora monitoring system across South African urban areas since 2019. This paper presents the inventory of preliminary investigation of the Ambrosia airborne pollen and the taxonomic identification of ragweed species.
Methods
Burkard volumetric spore traps for collecting pollen samples are set up in 9 South African cities (Johannesburg, Cape Town, Pretoria, Kimberley, Durban, Potchefstroom, Ermelo, Bloemfontein, and Gqeberha). Light microscopic identification was combined with environmental DNA metabarcoding analysis to confirm the species level of airborne Ambrosia at selected monitoring stations. Ragweed sensitisation was examined in Cape Town between February 2019 and February 2024, using Allergy Xplorer (ALEX2) multicomponent allergen array.
Results
Ambrosia pollen was detected in 5 aerobiological monitoring stations over the sampling period (Durban, Kimberley, Pretoria, Potchefstroom, Johannesburg). Periods of 4 consistent pollination years were observed in Kimberley (min: 1; max: 16 p.g/m3) and Durban (min: 26; max: 66 p.g/m3). In Pretoria, ragweed pollen was detected for 2 years (2020–2021; 2022–2023) with average total annuals (5-17 p.g/m3). A peak flowering period between March and April was observed in Potchefstroom, and several ragweed pollen peaks were present between the end of December and the beginning of May in Durban. The highest number of Ambrosia pollen grains was recorded in Potchefstroom, with 308 grains, and a maximum peak of 47 p.g/m3. eDNA metabarcoding confirmed the presence of Ambrosia artemisiifolia and A.trifida species. The overall prevalence of Ambrosia-sensitisation amongst 673 tests (age range 7–72 years) was 8.2% (55/673), with no significant difference in sensitisation patterns between age groups.
Conclusion
Our study confirms the need to monitor the spread of ragweed, and an increasing awareness of Ambrosia as an allergen of concern in Southern Africa. Extension of aerobiological networks and testing for Ambrosia sensitisation across urban and rural sites will be required.
{"title":"Ambrosia (ragweed) pollen — A growing aeroallergen of concern in South Africa","authors":"Dorra Gharbi PhD , Dilys Berman PhD , Frank H. Neumann PhD , Trevor Hill PhD , Siyavuya Sidla BSc , Sarel S. Cillers PhD , Jurgens Staats MD , Nanike Esterhuizen PhD , Linus Ajikah PhD , Moteng E. Moseri MSc , Lynne J. Quick PhD , Erin Hilmer BSc , Andri Van Aardt PhD , Juanette John PhD , Rebecca Garland PhD , Jemma Finch PhD , Werner Hoek MD , Marion Bamford PhD , Riaz Y. Seedat MD , Ahmed I. Manjra MD , Jonny Peter MD, PhD","doi":"10.1016/j.waojou.2024.101011","DOIUrl":"10.1016/j.waojou.2024.101011","url":null,"abstract":"<div><h3>Background</h3><div>Ragweed is an invasive, highly allergenic weed predicted to expand its habitat with warming global temperatures. Several <em>Ambrosia</em> species have been identified in South Africa for well over a century; however, its presence remained undetected by allergists and aerobiologists until the development of an extensive aerospora monitoring system across South African urban areas since 2019. This paper presents the inventory of preliminary investigation of the <em>Ambrosia</em> airborne pollen and the taxonomic identification of ragweed species.</div></div><div><h3>Methods</h3><div>Burkard volumetric spore traps for collecting pollen samples are set up in 9 South African cities (Johannesburg, Cape Town, Pretoria, Kimberley, Durban, Potchefstroom, Ermelo, Bloemfontein, and Gqeberha). Light microscopic identification was combined with environmental DNA metabarcoding analysis to confirm the species level of airborne <em>Ambrosia</em> at selected monitoring stations. Ragweed sensitisation was examined in Cape Town between February 2019 and February 2024, using Allergy Xplorer (ALEX<sup>2</sup>) multicomponent allergen array.</div></div><div><h3>Results</h3><div><em>Ambrosia</em> pollen was detected in 5 aerobiological monitoring stations over the sampling period (Durban, Kimberley, Pretoria, Potchefstroom, Johannesburg). Periods of 4 consistent pollination years were observed in Kimberley (min: 1; max: 16 p.g/m<sup>3</sup>) and Durban (min: 26; max: 66 p.g/m<sup>3</sup>). In Pretoria, ragweed pollen was detected for 2 years (2020–2021; 2022–2023) with average total annuals (5-17 p.g/m<sup>3</sup>). A peak flowering period between March and April was observed in Potchefstroom, and several ragweed pollen peaks were present between the end of December and the beginning of May in Durban. The highest number of <em>Ambrosia</em> pollen grains was recorded in Potchefstroom, with 308 grains, and a maximum peak of 47 p.g/m<sup>3</sup>. eDNA metabarcoding confirmed the presence of <em>Ambrosia artemisiifolia</em> and <em>A.trifida</em> species. The overall prevalence of <em>Ambrosia</em>-sensitisation amongst 673 tests (age range 7–72 years) was 8.2% (55/673), with no significant difference in sensitisation patterns between age groups.</div></div><div><h3>Conclusion</h3><div>Our study confirms the need to monitor the spread of ragweed, and an increasing awareness of Ambrosia as an allergen of concern in Southern Africa. Extension of aerobiological networks and testing for <em>Ambrosia</em> sensitisation across urban and rural sites will be required.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101011"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758811","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 : 2024-12-01DOI: 10.1016/j.waojou.2024.100998
Dodi Giulia MD , Di Filippo Paola MD , Di Ludovico Armando MD , Simeone Pasquale PhD , De Bellis Domenico MSc , D'ascanio Francesca MSc , Di Pillo Sabrina MD , Chiarelli Francesco PhD , Lanuti Paola PhD , Attanasi Marina PhD
Basophilic granulocytes, containing and releasing histamine after a specific allergy stimulation, are directly involved in IgE-mediated allergic reactions. CD63 is a transmembrane protein of secretory lysosomes of basophils and its upregulation is related with the release of histamine to the extracellular space during IgE-mediated allergic reactions. Basophil activation test (BAT) measures the activation of circulating basophils upon the in vitro stimulation of living blood cells with specific allergens. Such a test is particularly safe and reproducible and has recently emerged as a new promising diagnostic tool for allergic diseases.
BAT can be used to diagnose food allergy and represents a promising alternative to oral food challenge tests, especially in children as it is less invasive, safer, and cheaper than the gold standard tests. As a biomarker of tolerance and reactivity, it is also useful to monitor natural resolution and clinical response to immune-modulatory treatments. Regarding drug allergies, BAT is even the only possible applicable diagnostic tool for allergy reactions to some drugs, because of the lack of alternative test, or given that those commonly used are unreliable, or equivocal. Additionally, BAT allows to screen patients with more active urticarial and identify Hymenoptera-allergic patients with negative venom-specific immunoglobulin (Ig)E. In respiratory allergic diseases, BAT can facilitate the diagnosis of local allergic rhinitis and evaluate basophil allergen sensitivity in allergic asthma. Although IgE-sensitization in allergic asthma is usually demonstrated by skin prick test and specific IgE, those tests do not predict the clinical allergy contribution to asthma pathogenesis. To date, the potential of BAT in the diagnostic work-up of allergic diseases is well established, but a better standardization of its use is needed. This narrative review summarizes the state-of-the-art BAT technology and applications in pediatric allergic diseases, focusing on immune-related mechanisms and the BAT real clinical utility.
{"title":"Applications of basophil activation test in paediatric allergic diseases","authors":"Dodi Giulia MD , Di Filippo Paola MD , Di Ludovico Armando MD , Simeone Pasquale PhD , De Bellis Domenico MSc , D'ascanio Francesca MSc , Di Pillo Sabrina MD , Chiarelli Francesco PhD , Lanuti Paola PhD , Attanasi Marina PhD","doi":"10.1016/j.waojou.2024.100998","DOIUrl":"10.1016/j.waojou.2024.100998","url":null,"abstract":"<div><div>Basophilic granulocytes, containing and releasing histamine after a specific allergy stimulation, are directly involved in IgE-mediated allergic reactions. CD63 is a transmembrane protein of secretory lysosomes of basophils and its upregulation is related with the release of histamine to the extracellular space during IgE-mediated allergic reactions. Basophil activation test (BAT) measures the activation of circulating basophils upon the <em>in vitro</em> stimulation of living blood cells with specific allergens. Such a test is particularly safe and reproducible and has recently emerged as a new promising diagnostic tool for allergic diseases.</div><div>BAT can be used to diagnose food allergy and represents a promising alternative to oral food challenge tests, especially in children as it is less invasive, safer, and cheaper than the gold standard tests. As a biomarker of tolerance and reactivity, it is also useful to monitor natural resolution and clinical response to immune-modulatory treatments. Regarding drug allergies, BAT is even the only possible applicable diagnostic tool for allergy reactions to some drugs, because of the lack of alternative test, or given that those commonly used are unreliable, or equivocal. Additionally, BAT allows to screen patients with more active urticarial and identify Hymenoptera-allergic patients with negative venom-specific immunoglobulin (Ig)E. In respiratory allergic diseases, BAT can facilitate the diagnosis of local allergic rhinitis and evaluate basophil allergen sensitivity in allergic asthma. Although IgE-sensitization in allergic asthma is usually demonstrated by skin prick test and specific IgE, those tests do not predict the clinical allergy contribution to asthma pathogenesis. To date, the potential of BAT in the diagnostic work-up of allergic diseases is well established, but a better standardization of its use is needed. This narrative review summarizes the state-of-the-art BAT technology and applications in pediatric allergic diseases, focusing on immune-related mechanisms and the BAT real clinical utility.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100998"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903945","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 : 2024-12-01DOI: 10.1016/j.waojou.2024.101002
Ana M. Copaescu MD, FRCPC , Effie Mouhtouris BSc , Fiona James BBiomedSci , Michelle S.Y. Goh MBBS, FACD , Elizabeth J. Phillips MD, FRCPC, FRACP , Jason A. Trubiano MBBS, BBiomedSci, FRACP, PhD , for Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR)
Background
In an exploratory study to assess the potential to individualize T-cell diagnostics in antibiotic-associated severe T-cell mediated hypersensitivity, we focused on drug reaction with eosinophilia and systemic symptoms (DRESS) and the related cytokine outputs IL-4 and IL-5.
Methods
Patients with well-phenotyped RegiSCAR ≥4 DRESS, positive intradermal skin testing, and a previous negative IFN-γ Enzyme-Linked ImmunoSpot (ELISpot) assay were prospectively recruited. We specifically performed an ELISpot assay with IL-4 and IL-5 cytokine outputs. As comparative controls, these cytokine outputs were performed simultaneously in patients with a positive ex vivo IFN-γ release ELISpot result.
Results
Four antibiotic-associated DRESS cases were included. The IL-4 and IL-5 output ELISpot assay demonstrated various results among these patients, with at least 1 cytokine present in all the cases. As for the 2 controls with known positive IFN-γ release, compared to the IFN-γ secretion, the cytokine output using IL-4 and IL-5 showed an increased positivity.
Conclusion
In patients where the early response has suggested a TH2 response such as DRESS, IL-4 and IL-5 cytokine outputs could present an investigational advantage, including when IFN-γ is negative. In the future, larger prospective studies are required to understand the role of varied cytokine outputs in T-cell-mediated hypersensitivities.
{"title":"Exploring cytokine outputs for ex vivo diagnostics in drug reaction with eosinophilia and systemic symptoms (DRESS)","authors":"Ana M. Copaescu MD, FRCPC , Effie Mouhtouris BSc , Fiona James BBiomedSci , Michelle S.Y. Goh MBBS, FACD , Elizabeth J. Phillips MD, FRCPC, FRACP , Jason A. Trubiano MBBS, BBiomedSci, FRACP, PhD , for Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR)","doi":"10.1016/j.waojou.2024.101002","DOIUrl":"10.1016/j.waojou.2024.101002","url":null,"abstract":"<div><h3>Background</h3><div>In an exploratory study to assess the potential to individualize T-cell diagnostics in antibiotic-associated severe T-cell mediated hypersensitivity, we focused on drug reaction with eosinophilia and systemic symptoms (DRESS) and the related cytokine outputs IL-4 and IL-5.</div></div><div><h3>Methods</h3><div>Patients with well-phenotyped RegiSCAR ≥4 DRESS, positive intradermal skin testing, and a previous negative IFN-γ Enzyme-Linked ImmunoSpot (ELISpot) assay were prospectively recruited. We specifically performed an ELISpot assay with IL-4 and IL-5 cytokine outputs. As comparative controls, these cytokine outputs were performed simultaneously in patients with a positive <em>ex vivo</em> IFN-γ release ELISpot result.</div></div><div><h3>Results</h3><div>Four antibiotic-associated DRESS cases were included. The IL-4 and IL-5 output ELISpot assay demonstrated various results among these patients, with at least 1 cytokine present in all the cases. As for the 2 controls with known positive IFN-γ release, compared to the IFN-γ secretion, the cytokine output using IL-4 and IL-5 showed an increased positivity.</div></div><div><h3>Conclusion</h3><div>In patients where the early response has suggested a TH2 response such as DRESS, IL-4 and IL-5 cytokine outputs could present an investigational advantage, including when IFN-γ is negative. In the future, larger prospective studies are required to understand the role of varied cytokine outputs in T-cell-mediated hypersensitivities.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101002"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882685","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 : 2024-12-01DOI: 10.1016/j.waojou.2024.100996
Zhang Ping'an MD, Ma Yanliang MD, Chen Xi MD, Ma Yifan MD, Yang Luyang MM, Zhang Moqin MD, Gao Zhancheng PhD
Background
Susceptibility to relapse is an important feature of allergic bronchopulmonary aspergillosis (ABPA); early identification of patients at high risk of relapse is urgently needed. A practical score that classifies the severity of ABPA according to its prognosis is not available.
Methods
We retrospectively reviewed patients with a diagnosis of ABPA at our hospital between January 2010 and December 2022. Logistic regression analysis was used to investigate independent risk factors for ABPA treatment escalation and select the variables included in the final score.
Results
One hundred and three patients with ABPA were enrolled in this study. An eosinophil count >1000/μL, Aspergillus fumigatus–specific IgE (Sp-IgE) >3.5 kUA/L, expectoration of brownish-black mucus plugs, high-attenuation mucus (HAM) and a percentage of the predicted diffusing capacity of carbon monoxide (DLCO/pred) < 60% were independent risk factors for ABPA treatment escalation. Initial treatment with antifungals was an independent protective factor. The final scale, designated HEID, incorporated 4 dichotomized variables: HAM (H, 1 point); eosinophil count (E, cutoff 1000/μL, 1 point); Sp-IgE (I, cutoff 3.5 kUA/L, 1 point) and DLCO/pred (D, cutoff 60%, 1 point). A score of 0–1 point indicated a low relapse risk; 2–4 points indicated a high relapse risk.
Conclusion
This easy-to-use multidimensional grading system was capable of accurately classifying the risk of treatment escalation in ABPA.
{"title":"A multidimensional grading system for ABPA treatment escalation within the first year: The HEID score","authors":"Zhang Ping'an MD, Ma Yanliang MD, Chen Xi MD, Ma Yifan MD, Yang Luyang MM, Zhang Moqin MD, Gao Zhancheng PhD","doi":"10.1016/j.waojou.2024.100996","DOIUrl":"10.1016/j.waojou.2024.100996","url":null,"abstract":"<div><h3>Background</h3><div>Susceptibility to relapse is an important feature of allergic bronchopulmonary aspergillosis (ABPA); early identification of patients at high risk of relapse is urgently needed. A practical score that classifies the severity of ABPA according to its prognosis is not available.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed patients with a diagnosis of ABPA at our hospital between January 2010 and December 2022. Logistic regression analysis was used to investigate independent risk factors for ABPA treatment escalation and select the variables included in the final score.</div></div><div><h3>Results</h3><div>One hundred and three patients with ABPA were enrolled in this study. An eosinophil count >1000/μL, <em>Aspergillus fumigatus</em>–specific IgE (Sp-IgE) >3.5 kUA/L, expectoration of brownish-black mucus plugs, high-attenuation mucus (HAM) and a percentage of the predicted diffusing capacity of carbon monoxide (DLCO/pred) < 60% were independent risk factors for ABPA treatment escalation. Initial treatment with antifungals was an independent protective factor. The final scale, designated HEID, incorporated 4 dichotomized variables: HAM (H, 1 point); eosinophil count (E, cutoff 1000/μL, 1 point); Sp-IgE (I, cutoff 3.5 kUA/L, 1 point) and DLCO/pred (D, cutoff 60%, 1 point). A score of 0–1 point indicated a low relapse risk; 2–4 points indicated a high relapse risk.</div></div><div><h3>Conclusion</h3><div>This easy-to-use multidimensional grading system was capable of accurately classifying the risk of treatment escalation in ABPA.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100996"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748468","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 : 2024-12-01DOI: 10.1016/j.waojou.2024.101005
Ju Hee Kim MD , Eun Kyo Ha MD , Jeewon Shin MD , Nahyun Lee BE , Bo Eun Han BE , Man Yong Han MD , Eun Lee MD, PhD
Background
Understanding the trends of anaphylaxis and risk factors associated with its recurrence is essential for the effective management and prevention of this condition.
Objective
This study aimed to analyze the prevalence trends of anaphylaxis and identify risk factors for recurrence, with a focus on the influence of neighborhood deprivation and comorbidities, across all age groups.
Methods
We conducted a retrospective administrative cohort study on anaphylaxis utilizing the National Health Insurance-National Sample Cohort (NHIS-NSC) database in Korea (2002–2019). Anaphylaxis was defined with ICD-10 codes for the diagnosis combined with prescription codes. The Neighborhood Deprivation Index was used to identify the risk of recurrent anaphylaxis. Trends in the annual prevalence and recurrence of anaphylaxis were assessed through joinpoint regression and Cox proportional hazard models.
Results
Out of the 1,137,861 individuals studied, 37,012 (3.25%) cases of anaphylaxis were identified. Among these, 5783 individuals (15.6%) experienced a recurrence, half of them experiencing it within the first year after the initial episode. The highest incidence of anaphylaxis was observed in children and adolescents, followed by middle-aged adults. A rapid increase in anaphylaxis cases was observed from 2002 to 2006 (Annual Percentage Change [APC], 33.2), followed by a more gradual increase until 2013 (APC, 12.8), and a stable trend from 2013 to 2019 (APC, 0.61). Males and adult age groups exhibited an increased risk of recurrence. Living in an area with neighborhood deprivation and the presence of comorbid conditions were associated with increased recurrence risk.
Conclusions
The increasing prevalence of anaphylaxis and its association with certain risk factors calls for targeted intervention. Addressing neighborhood deprivation and comorbid conditions may aid in reducing the recurrence and overall burden of anaphylaxis.
{"title":"National trends in the prevalence and recurrence of anaphylaxis across all ages: The role of neighborhood deprivation and comorbidity (2002–2019)","authors":"Ju Hee Kim MD , Eun Kyo Ha MD , Jeewon Shin MD , Nahyun Lee BE , Bo Eun Han BE , Man Yong Han MD , Eun Lee MD, PhD","doi":"10.1016/j.waojou.2024.101005","DOIUrl":"10.1016/j.waojou.2024.101005","url":null,"abstract":"<div><h3>Background</h3><div>Understanding the trends of anaphylaxis and risk factors associated with its recurrence is essential for the effective management and prevention of this condition.</div></div><div><h3>Objective</h3><div>This study aimed to analyze the prevalence trends of anaphylaxis and identify risk factors for recurrence, with a focus on the influence of neighborhood deprivation and comorbidities, across all age groups.</div></div><div><h3>Methods</h3><div>We conducted a retrospective administrative cohort study on anaphylaxis utilizing the National Health Insurance-National Sample Cohort (NHIS-NSC) database in Korea (2002–2019). Anaphylaxis was defined with ICD-10 codes for the diagnosis combined with prescription codes. The Neighborhood Deprivation Index was used to identify the risk of recurrent anaphylaxis. Trends in the annual prevalence and recurrence of anaphylaxis were assessed through joinpoint regression and Cox proportional hazard models.</div></div><div><h3>Results</h3><div>Out of the 1,137,861 individuals studied, 37,012 (3.25%) cases of anaphylaxis were identified. Among these, 5783 individuals (15.6%) experienced a recurrence, half of them experiencing it within the first year after the initial episode. The highest incidence of anaphylaxis was observed in children and adolescents, followed by middle-aged adults. A rapid increase in anaphylaxis cases was observed from 2002 to 2006 (Annual Percentage Change [APC], 33.2), followed by a more gradual increase until 2013 (APC, 12.8), and a stable trend from 2013 to 2019 (APC, 0.61). Males and adult age groups exhibited an increased risk of recurrence. Living in an area with neighborhood deprivation and the presence of comorbid conditions were associated with increased recurrence risk.</div></div><div><h3>Conclusions</h3><div>The increasing prevalence of anaphylaxis and its association with certain risk factors calls for targeted intervention. Addressing neighborhood deprivation and comorbid conditions may aid in reducing the recurrence and overall burden of anaphylaxis.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101005"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759420","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 : 2024-12-01DOI: 10.1016/j.waojou.2024.101008
Jia Wang MD , Jinxin Hu MS , Dan Qin MD , Dan Han MD , Jiapeng Hu MD
Background
Asthma is a global chronic respiratory disease with complex pathogenesis. While current therapies offer some relief, they often fall short in effectively managing symptoms and preventing exacerbations for numerous patients. Thus, understanding its mechanisms and discovering new drug targets remains a pressing need for better treatment.
Methods
Using the GEO dataset, we screened differentially expressed genes (DEGs) in asthma patients' blood. Employing Summary Data-based Mendelian Randomization (SMR) and Two-Sample Mendelian Randomization (TSMR), we pinpointed asthma causal genes, causal DNA methylation sites, and methylation sites affecting gene expression, cross validated with at least 2 large-scale GWAS from each source. We utilized colocalization for genetic associations, meta-analysis for data integration, two-step MR for methylation-gene-asthma mediation mechanism. Druggability was evaluated using Open Target, virtual screening, and docking.
Results
Among the 954 DEGs found in asthma patients' blood, increased expression of CEP95 (discovery, OR_SMR = 0.94, 95% CI: 0.91–0.97), RBM6 (discovery, OR_SMR = 0.97, 95% CI: 0.95–0.99), and ITPKB (discovery, OR_SMR = 0.82, 95% CI: 0.74–0.92) in the blood decreased the risk of asthma, higher levels of HOXB-AS1 (discovery, OR_SMR = 1.05, 95% CI: 1.03–1.07), ETS1 (discovery, OR_SMR = 1.62, 95% CI: 1.29–2.04), and JAK2 (discovery, OR_SMR = 1.13, 95% CI: 1.06–1.21) in the blood increased the risk of asthma. Additionally, a total of 8 methylation sites on ITPKB, ETS1, and JAK2 were identified to influence asthma. An increase in methylation at site cg16265553 raised the risk of asthma partially by suppressing ITPKB expression. Similarly, increased methylation at cg13661497 reduced the asthma risk totally by suppressing JAK2 expression. The impact of CEP95, HOXB-AS1, and RBM6 expressions on asthma was further confirmed in lung tissues. Except for HOXB-AS1, all the other genes were potential druggable targets.
Conclusion
Our study highlighted that specific gene expressions and methylation sites significantly influence asthma risk and revealed a potential methylation-to-gene-to-asthma mechanism. This provided pivotal evidence for future targeted functional studies and the development of preventive and treatment strategies.
{"title":"A multi-omics Mendelian randomization identifies putatively causal genes and DNA methylation sites for asthma","authors":"Jia Wang MD , Jinxin Hu MS , Dan Qin MD , Dan Han MD , Jiapeng Hu MD","doi":"10.1016/j.waojou.2024.101008","DOIUrl":"10.1016/j.waojou.2024.101008","url":null,"abstract":"<div><h3>Background</h3><div>Asthma is a global chronic respiratory disease with complex pathogenesis. While current therapies offer some relief, they often fall short in effectively managing symptoms and preventing exacerbations for numerous patients. Thus, understanding its mechanisms and discovering new drug targets remains a pressing need for better treatment.</div></div><div><h3>Methods</h3><div>Using the GEO dataset, we screened differentially expressed genes (DEGs) in asthma patients' blood. Employing Summary Data-based Mendelian Randomization (SMR) and Two-Sample Mendelian Randomization (TSMR), we pinpointed asthma causal genes, causal DNA methylation sites, and methylation sites affecting gene expression, cross validated with at least 2 large-scale GWAS from each source. We utilized colocalization for genetic associations, meta-analysis for data integration, two-step MR for methylation-gene-asthma mediation mechanism. Druggability was evaluated using Open Target, virtual screening, and docking.</div></div><div><h3>Results</h3><div>Among the 954 DEGs found in asthma patients' blood, increased expression of CEP95 (discovery, OR_SMR = 0.94, 95% CI: 0.91–0.97), RBM6 (discovery, OR_SMR = 0.97, 95% CI: 0.95–0.99), and ITPKB (discovery, OR_SMR = 0.82, 95% CI: 0.74–0.92) in the blood decreased the risk of asthma, higher levels of HOXB-AS1 (discovery, OR_SMR = 1.05, 95% CI: 1.03–1.07), ETS1 (discovery, OR_SMR = 1.62, 95% CI: 1.29–2.04), and JAK2 (discovery, OR_SMR = 1.13, 95% CI: 1.06–1.21) in the blood increased the risk of asthma. Additionally, a total of 8 methylation sites on ITPKB, ETS1, and JAK2 were identified to influence asthma. An increase in methylation at site cg16265553 raised the risk of asthma partially by suppressing ITPKB expression. Similarly, increased methylation at cg13661497 reduced the asthma risk totally by suppressing JAK2 expression. The impact of CEP95, HOXB-AS1, and RBM6 expressions on asthma was further confirmed in lung tissues. Except for HOXB-AS1, all the other genes were potential druggable targets.</div></div><div><h3>Conclusion</h3><div>Our study highlighted that specific gene expressions and methylation sites significantly influence asthma risk and revealed a potential methylation-to-gene-to-asthma mechanism. This provided pivotal evidence for future targeted functional studies and the development of preventive and treatment strategies.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101008"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886318","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 : 2024-12-01DOI: 10.1016/j.waojou.2024.100971
Katharina Blumchen MD , Martin Hutter MSc , Sabine Schnadt MSc , Gregor Bushart PhD , Claudia Mailaender PhD
Background
Lacking causal treatment options in most cases, severe IgE-mediated food allergies (IgE-FA) are associated with a high burden of disease due to permanent risk of anaphylactic reactions after accidental allergen ingestion. To date, only few data comparing health resources and burden of disease between the pediatric and adult population are available.
Objective
Our survey aimed to assess the care situation of pediatric and adult patients with severe, self-reported physician-diagnosed IgE-FA.
Methods
The survey was conducted via an online questionnaire consisting of 32 items covering participant demographics, comorbidities, triggers, utilization of health resources, current management and burden of disease of FA, according to age groups (<18 years: proxy report by parents or ≥ 18 years: self-report by adults).
Results
A total of 367 participants (n = 237 children/parents, n = 130 adults) with self-reported physician-diagnosed IgE-FA and physician-prescribed adrenalin autoinjector were enrolled. Emergency training and having an emergency action plan were significantly more common in the pediatric group (81.4%) than in the adult group (36.2%). Children had clearer medical contact points (pediatrician or [pediatric] pulmonologist, 89.0%), while adults visited a variety of specialized physicians according to their FA-related symptoms. Adults were more unsatisfied with their overall coping-strategy for allergen avoidance (18.5%), daily FA management (27.9%), and treating physician (34.4%) than the pediatric group (2.6%/17.0%/14.8%, respectively, p < 0.05).
Discussion
Our data reveal a general undersupply for severe IgE-FA in Germany, with adults being significantly more affected. This may lead to the reported higher burden of disease in this age group. Increasing clearer medical contact points (eg, qualified allergologists specialized in food allergy)—especially for the adult patient population, finding available therapeutic options for this group of patients, and increasing the awareness of severe food allergy in the general population might overcome this problem.
{"title":"Management and disease burden of children and adults with severe IgE-mediated food allergy: Are adults the lost population?","authors":"Katharina Blumchen MD , Martin Hutter MSc , Sabine Schnadt MSc , Gregor Bushart PhD , Claudia Mailaender PhD","doi":"10.1016/j.waojou.2024.100971","DOIUrl":"10.1016/j.waojou.2024.100971","url":null,"abstract":"<div><h3>Background</h3><div>Lacking causal treatment options in most cases, severe IgE-mediated food allergies (IgE-FA) are associated with a high burden of disease due to permanent risk of anaphylactic reactions after accidental allergen ingestion. To date, only few data comparing health resources and burden of disease between the pediatric and adult population are available.</div></div><div><h3>Objective</h3><div>Our survey aimed to assess the care situation of pediatric and adult patients with severe, self-reported physician-diagnosed IgE-FA.</div></div><div><h3>Methods</h3><div>The survey was conducted via an online questionnaire consisting of 32 items covering participant demographics, comorbidities, triggers, utilization of health resources, current management and burden of disease of FA, according to age groups (<18 years: proxy report by parents or ≥ 18 years: self-report by adults).</div></div><div><h3>Results</h3><div>A total of 367 participants (n = 237 children/parents, n = 130 adults) with self-reported physician-diagnosed IgE-FA and physician-prescribed adrenalin autoinjector were enrolled. Emergency training and having an emergency action plan were significantly more common in the pediatric group (81.4%) than in the adult group (36.2%). Children had clearer medical contact points (pediatrician or [pediatric] pulmonologist, 89.0%), while adults visited a variety of specialized physicians according to their FA-related symptoms. Adults were more unsatisfied with their overall coping-strategy for allergen avoidance (18.5%), daily FA management (27.9%), and treating physician (34.4%) than the pediatric group (2.6%/17.0%/14.8%, respectively, p < 0.05).</div></div><div><h3>Discussion</h3><div>Our data reveal a general undersupply for severe IgE-FA in Germany, with adults being significantly more affected. This may lead to the reported higher burden of disease in this age group. Increasing clearer medical contact points (eg, qualified allergologists specialized in food allergy)—especially for the adult patient population, finding available therapeutic options for this group of patients, and increasing the awareness of severe food allergy in the general population might overcome this problem.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100971"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958861","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 : 2024-12-01DOI: 10.1016/j.waojou.2024.101010
Angela Pinot de Moira PhD, Adnan Custovic MD, PhD, FMedSci
Asthma is a complex, heterogeneous condition, broadly characterized by chronic airway inflammation with variable expiratory airflow limitation, but with several subtypes underpinned by different (although likely overlapping) pathological mechanisms. It is one of the most common chronic diseases of childhood and represents a significant cost for healthcare systems and affected families. Evidence suggests that a disproportionate proportion of this burden falls on families from disadvantaged socioeconomic circumstances (SECs).
In this review, we describe the extent to which growing up in disadvantaged SECs is associated with an increased risk of childhood asthma diagnosis and asthma outcomes, including how this differs geographically and across different asthma subtypes. We also discuss the complex and interdependent mediating pathways that may link disadvantaged SECs with childhood asthma and asthma-related outcomes.
In high-income countries (HICs), there is a fairly consistent association between growing up in disadvantaged SECs and increased prevalence of childhood asthma. However, evidence suggests that this social patterning differs across different asthma subtypes, with asthma phenotypes associated with disadvantaged SECs being less likely to be associated with atopy and more likely to begin in infancy and persist into adolescence. Disadvantaged SECs are also associated with worse asthma outcomes, which may contribute to the persistence of symptoms among disadvantaged children.
In low- and middle-income countries (LMICs), the patterns are more variable and data more limited, but there is some evidence that disadvantaged SECs and atopic asthma are similarly negatively associated. There are also clear disparities in asthma outcomes, with LMICs having disproportionately high asthma-related morbidity and mortality, despite having lower asthma prevalence. A lack of accessibility to essential medication and appropriate care no doubt contributes to these disparities.
The pathways leading to social inequalities in asthma are complex and interdependent, and as yet not fully understood. There is a clear need for further research into the relative importance of potential mediating pathways, including how these vary across the life course and across asthma subtypes. A stronger understanding of these pathways will help identify the most effective policy entry points for intervention, ultimately reducing inequalities across the life course.
{"title":"Social inequalities in childhood asthma","authors":"Angela Pinot de Moira PhD, Adnan Custovic MD, PhD, FMedSci","doi":"10.1016/j.waojou.2024.101010","DOIUrl":"10.1016/j.waojou.2024.101010","url":null,"abstract":"<div><div>Asthma is a complex, heterogeneous condition, broadly characterized by chronic airway inflammation with variable expiratory airflow limitation, but with several subtypes underpinned by different (although likely overlapping) pathological mechanisms. It is one of the most common chronic diseases of childhood and represents a significant cost for healthcare systems and affected families. Evidence suggests that a disproportionate proportion of this burden falls on families from disadvantaged socioeconomic circumstances (SECs).</div><div>In this review, we describe the extent to which growing up in disadvantaged SECs is associated with an increased risk of childhood asthma diagnosis and asthma outcomes, including how this differs geographically and across different asthma subtypes. We also discuss the complex and interdependent mediating pathways that may link disadvantaged SECs with childhood asthma and asthma-related outcomes.</div><div>In high-income countries (HICs), there is a fairly consistent association between growing up in disadvantaged SECs and increased prevalence of childhood asthma. However, evidence suggests that this social patterning differs across different asthma subtypes, with asthma phenotypes associated with disadvantaged SECs being less likely to be associated with atopy and more likely to begin in infancy and persist into adolescence. Disadvantaged SECs are also associated with worse asthma outcomes, which may contribute to the persistence of symptoms among disadvantaged children.</div><div>In low- and middle-income countries (LMICs), the patterns are more variable and data more limited, but there is some evidence that disadvantaged SECs and atopic asthma are similarly negatively associated. There are also clear disparities in asthma outcomes, with LMICs having disproportionately high asthma-related morbidity and mortality, despite having lower asthma prevalence. A lack of accessibility to essential medication and appropriate care no doubt contributes to these disparities.</div><div>The pathways leading to social inequalities in asthma are complex and interdependent, and as yet not fully understood. There is a clear need for further research into the relative importance of potential mediating pathways, including how these vary across the life course and across asthma subtypes. A stronger understanding of these pathways will help identify the most effective policy entry points for intervention, ultimately reducing inequalities across the life course.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101010"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759419","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}
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