{"title":"Chronic rhinosinusitis and the development of non-cystic fibrosis bronchiectasis","authors":"Nien-Yi Wu RN , Hui-Chin Chang MLS , Shuo-Yan Gau MD, FRSPH","doi":"10.1016/j.jaip.2025.01.008","DOIUrl":"10.1016/j.jaip.2025.01.008","url":null,"abstract":"","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"13 3","pages":"Page 720"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jaip.2024.11.016
Grace Hardwick BS , Twan Sia BA , Leeon Bacchus BA , Xiaolin Jia MD , Andrew R. Chin PhD , Nasim Khavari MD , Marwa Abu El Haija MD , Sean McGhee MD , R. Sharon Chinthrajah MD , John Leung MD , Sayantani B. Sindher MD
{"title":"Management of eosinophilic esophagitis in pediatric patients undergoing oral immunotherapy for food allergies: A 2-center case series","authors":"Grace Hardwick BS , Twan Sia BA , Leeon Bacchus BA , Xiaolin Jia MD , Andrew R. Chin PhD , Nasim Khavari MD , Marwa Abu El Haija MD , Sean McGhee MD , R. Sharon Chinthrajah MD , John Leung MD , Sayantani B. Sindher MD","doi":"10.1016/j.jaip.2024.11.016","DOIUrl":"10.1016/j.jaip.2024.11.016","url":null,"abstract":"","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"13 3","pages":"Pages 702-704"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ibuprofen is a main cause of drug hypersensitivity reactions in children. The gold standard for diagnosis is the drug provocation test (DPT).
Objective
We aimed to create a clinical risk-stratification tool to guide this high-risk procedure.
Methods
We prospectively recruited children with suspected ibuprofen hypersensitivity between January 2017 and March 2024. Using stepwise bidirectional multivariable logistic regression, we calculated a predictive score for a positive ibuprofen DPT.
Results
Eighty-two patients with a median age of 5.9 years (interquartile range: 3.4-11.1 years) had an ibuprofen DPT. Eighteen (22.0%) patients had a positive challenge, with an anaphylactic reaction for 11 (61.1%). The I3A score (acronym for ibuprofen, 3As: angioedema, anaphylaxis, age, cutoff of 3) encompasses the following items: angioedema (2 points), anaphylaxis (1 point), and age at reaction ≥10 years old (1 point). The area under the curve of the I3A score was 0.84, and the optimal cutoff of <3 conferred a sensitivity of 84.4% (95% confidence interval [CI]: 66.7%-100.0%) and a specificity of 83.3% (95% CI: 75.0%-92.2%). The negative predictive value was estimated at 94.7% (95% CI: 90.0%-100.0%), and the positive predictive value at 60.0% (95% CI: 46.2%-76.2%). The relative risk of reacting to a challenge in the group I3A 3-4 compared with 0-2 was 11.4 (95% CI: 3.62%-35.7%, P < .001). Anaphylaxis after DPT was observed in 9 of 25 (36.0% [95% CI: 16.0%-56.0%]) in the high-risk group as compared with 2 of 57 (3.5% [95% CI: 0.0%-8.8%]) in the low-risk group (relative risk 10.3 [95% CI: 2.4%-43.5%]).
Conclusions
We generated a risk-stratification tool to identify children at low risk of reacting to ibuprofen challenges. Further validation is required in external cohorts.
{"title":"Guiding Drug Provocation Testing for Ibuprofen Hypersensitivity in a Pediatric Population: Development of the I3A Risk-Stratification Tool","authors":"Florian Stehlin MD , Connor Prosty MD , Angela Mulé BSc , Ibtihal Al-Otaibi MD , Luca Delli Colli MD , Judy Gaffar MD , Joshua Yu MD , Derek Lanoue MD, MEcon , Ana-Maria Copaescu MD , Moshe Ben-Shoshan MD, MSc","doi":"10.1016/j.jaip.2024.11.022","DOIUrl":"10.1016/j.jaip.2024.11.022","url":null,"abstract":"<div><h3>Background</h3><div>Ibuprofen is a main cause of drug hypersensitivity reactions in children. The gold standard for diagnosis is the drug provocation test (DPT).</div></div><div><h3>Objective</h3><div>We aimed to create a clinical risk-stratification tool to guide this high-risk procedure.</div></div><div><h3>Methods</h3><div>We prospectively recruited children with suspected ibuprofen hypersensitivity between January 2017 and March 2024. Using stepwise bidirectional multivariable logistic regression, we calculated a predictive score for a positive ibuprofen DPT.</div></div><div><h3>Results</h3><div>Eighty-two patients with a median age of 5.9 years (interquartile range: 3.4-11.1 years) had an ibuprofen DPT. Eighteen (22.0%) patients had a positive challenge, with an anaphylactic reaction for 11 (61.1%). The I3A score (acronym for ibuprofen, 3As: angioedema, anaphylaxis, age, cutoff of 3) encompasses the following items: angioedema (2 points), anaphylaxis (1 point), and age at reaction ≥10 years old (1 point). The area under the curve of the I3A score was 0.84, and the optimal cutoff of <3 conferred a sensitivity of 84.4% (95% confidence interval [CI]: 66.7%-100.0%) and a specificity of 83.3% (95% CI: 75.0%-92.2%). The negative predictive value was estimated at 94.7% (95% CI: 90.0%-100.0%), and the positive predictive value at 60.0% (95% CI: 46.2%-76.2%). The relative risk of reacting to a challenge in the group I3A 3-4 compared with 0-2 was 11.4 (95% CI: 3.62%-35.7%, <em>P</em> < .001). Anaphylaxis after DPT was observed in 9 of 25 (36.0% [95% CI: 16.0%-56.0%]) in the high-risk group as compared with 2 of 57 (3.5% [95% CI: 0.0%-8.8%]) in the low-risk group (relative risk 10.3 [95% CI: 2.4%-43.5%]).</div></div><div><h3>Conclusions</h3><div>We generated a risk-stratification tool to identify children at low risk of reacting to ibuprofen challenges. Further validation is required in external cohorts.</div></div>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"13 3","pages":"Pages 583-593.e3"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jaip.2024.12.021
Ha Young Jang PhD , Boyoon Choi PhD , In-Wha Kim PhD , Hye Ryun Kang MD, PhD , Jung Mi Oh PharmD
Background
The development of hypersensitivity reactions (HSRs) to carboplatin can interrupt anticancer treatment and may shorten patient survival. Several studies have evaluated the risk factors for carboplatin HSRs, but the results have been inconclusive.
Objective
This systematic review and meta-analysis aimed to establish a consensus on the risk factors of HSRs to carboplatin in patients with cancer.
Methods
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, relevant studies were searched across MEDLINE, Embase, and Korean Medical Database. Inclusion criteria focused on original articles of case-control or cohort studies that evaluated risk factors for carboplatin HSRs in patients with cancer. Exclusion criteria targeted articles with incomplete or overlapping data. The latest search and quality assessment of the included studies, using the Newcastle-Ottawa scale, was performed on February 1, 2023.
Results
Among 1,182 articles identified, 19 studies were included in the final systematic review and meta-analysis. The identified risk factors for carboplatin hypersensitivity included a history of allergy to medicines, food, or environmental factors (odds ratio [OR] = 1.76; 95% CI, 1.46-2.12), BRCA mutation (OR = 4.03; 95% CI, 2.00-8.13), carboplatin free interval of 12 months or more (OR = 4.93; 95% CI, 2.89-8.40), increased cumulative dose (standardized mean difference, 0.58; 95% CI, 0.41-0.75), relapse (OR = 2.26; 95% CI, 1.58-3.25), and younger age (standardized mean difference, –0.15; 95% CI, –0.26 to –0.03).
Conclusions
To our knowledge, this meta-analysis provides the first comprehensive quantitative evaluation of risk factors for carboplatin HSRs in patients with cancer. These findings can guide the development of personalized risk assessment tools and preventive strategies, potentially improving patient safety and treatment outcomes in carboplatin-based chemotherapy.
{"title":"Risk Factors of Hypersensitivity Reactions to Carboplatin: A Systematic Review and Meta-Analysis","authors":"Ha Young Jang PhD , Boyoon Choi PhD , In-Wha Kim PhD , Hye Ryun Kang MD, PhD , Jung Mi Oh PharmD","doi":"10.1016/j.jaip.2024.12.021","DOIUrl":"10.1016/j.jaip.2024.12.021","url":null,"abstract":"<div><h3>Background</h3><div>The development of hypersensitivity reactions (HSRs) to carboplatin can interrupt anticancer treatment and may shorten patient survival. Several studies have evaluated the risk factors for carboplatin HSRs, but the results have been inconclusive.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis aimed to establish a consensus on the risk factors of HSRs to carboplatin in patients with cancer.</div></div><div><h3>Methods</h3><div>Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, relevant studies were searched across MEDLINE, Embase, and Korean Medical Database. Inclusion criteria focused on original articles of case-control or cohort studies that evaluated risk factors for carboplatin HSRs in patients with cancer. Exclusion criteria targeted articles with incomplete or overlapping data. The latest search and quality assessment of the included studies, using the Newcastle-Ottawa scale, was performed on February 1, 2023.</div></div><div><h3>Results</h3><div>Among 1,182 articles identified, 19 studies were included in the final systematic review and meta-analysis. The identified risk factors for carboplatin hypersensitivity included a history of allergy to medicines, food, or environmental factors (odds ratio [OR] = 1.76; 95% CI, 1.46-2.12), <em>BRCA</em> mutation (OR = 4.03; 95% CI, 2.00-8.13), carboplatin free interval of 12 months or more (OR = 4.93; 95% CI, 2.89-8.40), increased cumulative dose (standardized mean difference, 0.58; 95% CI, 0.41-0.75), relapse (OR = 2.26; 95% CI, 1.58-3.25), and younger age (standardized mean difference, –0.15; 95% CI, –0.26 to –0.03).</div></div><div><h3>Conclusions</h3><div>To our knowledge, this meta-analysis provides the first comprehensive quantitative evaluation of risk factors for carboplatin HSRs in patients with cancer. These findings can guide the development of personalized risk assessment tools and preventive strategies, potentially improving patient safety and treatment outcomes in carboplatin-based chemotherapy.</div></div>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"13 3","pages":"Pages 610-618.e10"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/S2213-2198(25)00108-4
{"title":"March 2025 Practice Notes","authors":"","doi":"10.1016/S2213-2198(25)00108-4","DOIUrl":"10.1016/S2213-2198(25)00108-4","url":null,"abstract":"","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"13 3","pages":"Pages A19-A20"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jaip.2024.10.045
Huqun Li MD , Chongshu Wang MD , Cuilian Guo MD
Background
Tezepelumab has shown promising efficacy for adult patients with severe asthma since its approval. However, the post-marketing safety evaluation of tezepelumab is currently lacking.
Objective
To investigate the post-marketing safety of tezepelumab based on the US Food and Drug Administration Adverse Event Reporting System database.
Methods
Adverse events (AEs) reported from January 2022 to December 2023 were extracted from the US Food and Drug Administration Adverse Event Reporting System database. Disproportionality analysis by reporting odds ratio and empirical Bayesian geometric mean was performed to detect potential AEs related to tezepelumab. We also assessed clinical characteristics and time to onset of AEs.
Results
A total of 1,699 tezepelumab-related AE reports were identified during the study period. We detected 30 tezepelumab-related AE signals by simultaneously applying the two algorithms. At the system organ class level, the most common system organ class related to tezepelumab was respiratory, thoracic, and mediastinal disorders. At the preferred term level, common AEs including arthralgia and back pain were detected, which were also documented in the label of tezepelumab and clinical trials. New unexpected AEs such as chest pain and myalgia were also identified. Median time to onset of tezepelumab-related AEs was 7.5 days and most AEs occurred within the first 1 month after tezepelumab initiation.
Conclusions
This study presents a comprehensive evaluation of the post-marketing safety of tezepelumab in the real-world setting. Our findings will provide valuable evidence for future clinical studies and management of safety issues of tezepelumab.
{"title":"A Pharmacovigilance Analysis of Post-Marketing Safety of Tezepelumab","authors":"Huqun Li MD , Chongshu Wang MD , Cuilian Guo MD","doi":"10.1016/j.jaip.2024.10.045","DOIUrl":"10.1016/j.jaip.2024.10.045","url":null,"abstract":"<div><h3>Background</h3><div>Tezepelumab has shown promising efficacy for adult patients with severe asthma since its approval. However, the post-marketing safety evaluation of tezepelumab is currently lacking.</div></div><div><h3>Objective</h3><div>To investigate the post-marketing safety of tezepelumab based on the US Food and Drug Administration Adverse Event Reporting System database.</div></div><div><h3>Methods</h3><div>Adverse events (AEs) reported from January 2022 to December 2023 were extracted from the US Food and Drug Administration Adverse Event Reporting System database. Disproportionality analysis by reporting odds ratio and empirical Bayesian geometric mean was performed to detect potential AEs related to tezepelumab. We also assessed clinical characteristics and time to onset of AEs.</div></div><div><h3>Results</h3><div>A total of 1,699 tezepelumab-related AE reports were identified during the study period. We detected 30 tezepelumab-related AE signals by simultaneously applying the two algorithms. At the system organ class level, the most common system organ class related to tezepelumab was respiratory, thoracic, and mediastinal disorders. At the preferred term level, common AEs including arthralgia and back pain were detected, which were also documented in the label of tezepelumab and clinical trials. New unexpected AEs such as chest pain and myalgia were also identified. Median time to onset of tezepelumab-related AEs was 7.5 days and most AEs occurred within the first 1 month after tezepelumab initiation.</div></div><div><h3>Conclusions</h3><div>This study presents a comprehensive evaluation of the post-marketing safety of tezepelumab in the real-world setting. Our findings will provide valuable evidence for future clinical studies and management of safety issues of tezepelumab.</div></div>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"13 3","pages":"Pages 551-558.e6"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jaip.2024.12.002
Jie Yin MD , Kevin M. Hayes BS , Mei-Sing Ong PhD , Joseph P. Mizgerd ScD , Charlotte Cunningham-Rundles MD, PhD , Isabel Dominguez PhD , Sara Barmettler MD , Jocelyn R. Farmer MD, PhD , Paul J. Maglione MD, PhD
Background
NFKB1 encodes p105, which is processed to p50 to mediate canonical nuclear factor-κB (NF-κB) signaling. Although NF-κB is a central driver of inflammation and heterozygous NFKB1 variants are considered the most common monogenic etiologies of common variable immunodeficiency (CVID), few studies have explored how NFKB1 variants shape clinical course or inflammation in CVID.
Objective
We leveraged a regional cohort of patients with CVID with and without heterozygous NFKB1 variants to assess how clinical and inflammatory features of CVID are shaped by the presence of these variants.
Methods
We compared clinical complications, immunologic features, and plasma cytokine levels of 15 patients with CVID with heterozygous NFKB1 variants and 77 genetically undefined patients with CVID from the same referral base. We also assessed differences between patients with CVID with frameshift or nonsense NFKB1 variants compared with those with missense NFKB1 variants.
Results
We found patients with CVID with heterozygous NFKB1 variants to have increased autoimmune disease, bronchiectasis, gastrointestinal infections, inflammatory bowel disease, and plasma cytokines. These findings were more pronounced and included elevation of monocytes in patients with CVID with frameshift or nonsense NFKB1 variants relative to those with missense NFKB1 variants.
Conclusions
In a regional cohort, heterozygous NFKB1 variants were associated with worsened CVID clinical course and increased evidence of inflammation in the blood. Patients with CVID with frameshift or nonsense NFKB1 variants had more significant increases in noninfectious complications and peripheral monocytes than those with missense NFKB1 variants. Presence of pathogenic NFKB1 variants in patients with CVID may worsen the disease course and warrant closer monitoring.
{"title":"Common Variable Immunodeficiency Clinical Manifestations Are Shaped by Presence and Type of Heterozygous NFKB1 Variants","authors":"Jie Yin MD , Kevin M. Hayes BS , Mei-Sing Ong PhD , Joseph P. Mizgerd ScD , Charlotte Cunningham-Rundles MD, PhD , Isabel Dominguez PhD , Sara Barmettler MD , Jocelyn R. Farmer MD, PhD , Paul J. Maglione MD, PhD","doi":"10.1016/j.jaip.2024.12.002","DOIUrl":"10.1016/j.jaip.2024.12.002","url":null,"abstract":"<div><h3>Background</h3><div><em>NFKB1</em> encodes p105, which is processed to p50 to mediate canonical nuclear factor-κB (NF-κB) signaling. Although NF-κB is a central driver of inflammation and heterozygous <em>NFKB1</em> variants are considered the most common monogenic etiologies of common variable immunodeficiency (CVID), few studies have explored how <em>NFKB1</em> variants shape clinical course or inflammation in CVID.</div></div><div><h3>Objective</h3><div>We leveraged a regional cohort of patients with CVID with and without heterozygous <em>NFKB1</em> variants to assess how clinical and inflammatory features of CVID are shaped by the presence of these variants.</div></div><div><h3>Methods</h3><div>We compared clinical complications, immunologic features, and plasma cytokine levels of 15 patients with CVID with heterozygous <em>NFKB1</em> variants and 77 genetically undefined patients with CVID from the same referral base. We also assessed differences between patients with CVID with frameshift or nonsense <em>NFKB1</em> variants compared with those with missense <em>NFKB1</em> variants.</div></div><div><h3>Results</h3><div>We found patients with CVID with heterozygous <em>NFKB1</em> variants to have increased autoimmune disease, bronchiectasis, gastrointestinal infections, inflammatory bowel disease, and plasma cytokines. These findings were more pronounced and included elevation of monocytes in patients with CVID with frameshift or nonsense <em>NFKB1</em> variants relative to those with missense <em>NFKB1</em> variants.</div></div><div><h3>Conclusions</h3><div>In a regional cohort, heterozygous <em>NFKB1</em> variants were associated with worsened CVID clinical course and increased evidence of inflammation in the blood. Patients with CVID with frameshift or nonsense <em>NFKB1</em> variants had more significant increases in noninfectious complications and peripheral monocytes than those with missense <em>NFKB1</em> variants. Presence of pathogenic <em>NFKB1</em> variants in patients with CVID may worsen the disease course and warrant closer monitoring.</div></div>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"13 3","pages":"Pages 639-646"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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