The journal of allergy and clinical immunology. Global最新文献

英文中文

Urticaria unveiled in hereditary angioedema with carboxypeptidase N mutation

The journal of allergy and clinical immunology. Global

Pub Date : 2025-01-10 DOI: 10.1016/j.jacig.2025.100405

Pedro Giavina-Bianchi MD, PhD, Mara Giavina-Bianchi MD, PhD, Jorge Kalil MD, PhD

引用次数: 0

Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults

The journal of allergy and clinical immunology. Global

Pub Date : 2025-01-09 DOI: 10.1016/j.jacig.2025.100403

Shay Nemet MD , Daniel Elbirt MD , Ramon Cohen MD , Keren Mahlab-Guri MD , Shira Bezalel-Rosenberg MD , Ilan Asher MD , Aviv Talmon MD , Limor Rubin MD , Yaarit Ribak MD , Ruslan Sergienko MHA , Udi Nussinovitch MD, PhD , Yuval Tal MD, PhD , Oded Shamriz MD

Background

Very high serum IgE (≥1000 IU/mL) is reported in atopic disorders. However, data on its significance in nonallergic disorders are limited.

Objective

We aimed to analyze the diagnostic value of very high IgE in adults.

Methods

A retrospective nationwide study was conducted using the electronic database of Clalit Health Services, covering adults (≥18 years) treated between 2002 and 2022. Subjects with IgE ≥ 1000 IU/mL were compared to the controls with IgE < 100 IU/mL across 3 age groups (18-30, 31-64, and ≥65 years). Outcomes included eosinophilic, autoimmune, autoinflammatory, and cardiovascular disorders (CVD), cancer, and inborn errors of immunity (IEI). A multivariable Cox regression model determined statistical significance (P < .05).

Results

The study included 118,211 subjects: 110,116 controls and 8635 with very high IgE levels. Excluding insect sting and drug allergies, very high IgE was more common across all tested allergic disorders, with asthma showing the highest rate (64.49%). Univariable analysis showed higher prevalence of CVD (3.88% vs 2.72%, P < .001), eosinophilic disorders (0.42% vs 0.06%, P < .001), and IEI (0.35% vs 0.20%, P = .004) in the very high IgE group. Multivariable analysis revealed age-dependent significant results: higher CVD risk in ages 31-64 (hazard ratio = 1.249; 95% confidence interval, 1.054-1.481; P = .010) and borderline IEI association in ages 18-30 (hazard ratio = 1.802; 95% confidence interval, 0.978-3.321; P = .059). Risk of eosinophilic disorders was increased across all age groups (P < .001).

Conclusions

Very high IgE level of ≥1000 IU/mL is associated with increased risks of CVD, IEI, and eosinophilic disorders. Physicians should consider further assessment for these conditions in nonallergic patients with very high IgE levels.

{"title":"Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults","authors":"Shay Nemet MD , Daniel Elbirt MD , Ramon Cohen MD , Keren Mahlab-Guri MD , Shira Bezalel-Rosenberg MD , Ilan Asher MD , Aviv Talmon MD , Limor Rubin MD , Yaarit Ribak MD , Ruslan Sergienko MHA , Udi Nussinovitch MD, PhD , Yuval Tal MD, PhD , Oded Shamriz MD","doi":"10.1016/j.jacig.2025.100403","DOIUrl":"10.1016/j.jacig.2025.100403","url":null,"abstract":"<div><h3>Background</h3><div>Very high serum IgE (≥1000 IU/mL) is reported in atopic disorders. However, data on its significance in nonallergic disorders are limited.</div></div><div><h3>Objective</h3><div>We aimed to analyze the diagnostic value of very high IgE in adults.</div></div><div><h3>Methods</h3><div>A retrospective nationwide study was conducted using the electronic database of Clalit Health Services, covering adults (≥18 years) treated between 2002 and 2022. Subjects with IgE ≥ 1000 IU/mL were compared to the controls with IgE < 100 IU/mL across 3 age groups (18-30, 31-64, and ≥65 years). Outcomes included eosinophilic, autoimmune, autoinflammatory, and cardiovascular disorders (CVD), cancer, and inborn errors of immunity (IEI). A multivariable Cox regression model determined statistical significance (<em>P</em> < .05).</div></div><div><h3>Results</h3><div>The study included 118,211 subjects: 110,116 controls and 8635 with very high IgE levels. Excluding insect sting and drug allergies, very high IgE was more common across all tested allergic disorders, with asthma showing the highest rate (64.49%). Univariable analysis showed higher prevalence of CVD (3.88% vs 2.72%, <em>P</em> < .001), eosinophilic disorders (0.42% vs 0.06%, <em>P</em> < .001), and IEI (0.35% vs 0.20%, <em>P</em> = .004) in the very high IgE group. Multivariable analysis revealed age-dependent significant results: higher CVD risk in ages 31-64 (hazard ratio = 1.249; 95% confidence interval, 1.054-1.481; <em>P</em> = .010) and borderline IEI association in ages 18-30 (hazard ratio = 1.802; 95% confidence interval, 0.978-3.321; <em>P</em> = .059). Risk of eosinophilic disorders was increased across all age groups (<em>P</em> < .001).</div></div><div><h3>Conclusions</h3><div>Very high IgE level of ≥1000 IU/mL is associated with increased risks of CVD, IEI, and eosinophilic disorders. Physicians should consider further assessment for these conditions in nonallergic patients with very high IgE levels.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100403"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Moving to lower-poverty neighborhoods offers broad benefits for children with asthma, regardless of sex or other baseline characteristics

The journal of allergy and clinical immunology. Global

Pub Date : 2025-01-07 DOI: 10.1016/j.jacig.2025.100402

Torie L. Grant MD, MHS , Laken C. Roberts Lavigne PhD, MPH , Craig Evan Pollack MD, MHS , Pete Cimbolic BA , Susan Balcer-Whaley MPH , Roger D. Peng PhD , Elizabeth C. Matsui MD, MHS , Corinne A. Keet MD, PhD

Background

It was previously found that moving to lower-poverty/higher-opportunity neighborhoods as part of a housing mobility program was associated with improvements in asthma exacerbations and symptoms among children with asthma. Whether some subsets of children with asthma experience a greater improvement in asthma morbidity after moving is unknown.

Objective

Our aim was to determine whether the benefits of moving to lower-poverty/higher-opportunity neighborhoods were concentrated in subsets of participants with asthma.

Methods

We conducted a secondary analysis of the participants in the Mobility Asthma Project. Generalized estimating equations were used to assess the association between moving and asthma exacerbations and maximum symptom days. Separately, these models were then stratified by sex, age, body mass index, allergic sensitization, asthma severity, and stress before the move to estimate stratum-specific odds ratios for moving.

Results

Participants broadly experienced a postmove reduction in odds of an exacerbation and maximum symptom days. Male children and children at a higher asthma controller medication treatment step experienced a greater reduction in maximum symptom days with moving.

Conclusion

Children with asthma experience a reduction in odds of an exacerbation and symptoms after moving to lower-poverty/higher-opportunity neighborhoods. These improvements in asthma outcomes are seen regardless of baseline sex, age, body mass index, allergic sensitization, asthma severity, and premove stress.

{"title":"Moving to lower-poverty neighborhoods offers broad benefits for children with asthma, regardless of sex or other baseline characteristics","authors":"Torie L. Grant MD, MHS , Laken C. Roberts Lavigne PhD, MPH , Craig Evan Pollack MD, MHS , Pete Cimbolic BA , Susan Balcer-Whaley MPH , Roger D. Peng PhD , Elizabeth C. Matsui MD, MHS , Corinne A. Keet MD, PhD","doi":"10.1016/j.jacig.2025.100402","DOIUrl":"10.1016/j.jacig.2025.100402","url":null,"abstract":"<div><h3>Background</h3><div>It was previously found that moving to lower-poverty/higher-opportunity neighborhoods as part of a housing mobility program was associated with improvements in asthma exacerbations and symptoms among children with asthma. Whether some subsets of children with asthma experience a greater improvement in asthma morbidity after moving is unknown.</div></div><div><h3>Objective</h3><div>Our aim was to determine whether the benefits of moving to lower-poverty/higher-opportunity neighborhoods were concentrated in subsets of participants with asthma.</div></div><div><h3>Methods</h3><div>We conducted a secondary analysis of the participants in the Mobility Asthma Project. Generalized estimating equations were used to assess the association between moving and asthma exacerbations and maximum symptom days. Separately, these models were then stratified by sex, age, body mass index, allergic sensitization, asthma severity, and stress before the move to estimate stratum-specific odds ratios for moving.</div></div><div><h3>Results</h3><div>Participants broadly experienced a postmove reduction in odds of an exacerbation and maximum symptom days. Male children and children at a higher asthma controller medication treatment step experienced a greater reduction in maximum symptom days with moving.</div></div><div><h3>Conclusion</h3><div>Children with asthma experience a reduction in odds of an exacerbation and symptoms after moving to lower-poverty/higher-opportunity neighborhoods. These improvements in asthma outcomes are seen regardless of baseline sex, age, body mass index, allergic sensitization, asthma severity, and premove stress.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100402"},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143332869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phase 1 study of safety, tolerability, and efficacy of intradermal DNA vaccine ASP2390 in adults allergic to house dust mites

The journal of allergy and clinical immunology. Global

Pub Date : 2025-01-07 DOI: 10.1016/j.jacig.2025.100404

Thomas Kayser MD, BS , Ronald Smulders MD, PhD , Tomohiro Kusawake PhD , Erik Wambre PhD , Gurunadh R. Chichili PhD , Mary B. Blauwet DrPH , Anna Spence MS , Melanie Patton BS , Rima Tabash PhD , Hannah A. DeBerg PhD , Sugandhika Khosa MS , Philipp Badorrek MD , Jens M. Hohlfeld MD , Brian C. Ferslew PharmD, PhD

Background

House dust mite (HDM) allergies are prevalent, yet current treatments like allergen avoidance, pharmacotherapy, and conventional allergen immunotherapy present limitations. The novel LAMP (lysosomal-associated membrane protein)-based DNA vaccine ASP2390 targets major HDM allergens, potentially shifting immune responses toward nonallergic pathways and minimizing the risk of atopy, with positive safety and efficacy signals in preclinical models.

Objective

We evaluated the safety, tolerability, and efficacy of first-in-human intradermal ASP2390 in adults with HDM allergy.

Methods

A randomized, double-blind, placebo-controlled phase 1 trial was conducted in adults with HDM-induced allergic rhinitis. Participants received either 1 mg or 4 mg of ASP2390 or placebo intradermally once weekly for 12 weeks, with safety, tolerability, and pharmacodynamic responses assessed over a 63-week period, including early-phase clinical effects assessed via HDM exposure in an allergen challenge chamber.

Results

Twenty-eight adults (mean age, 26.9 years; 23 male participants), with 7 receiving 1 mg and 13 receiving 4 mg ASP2390, 8 receiving placebo, showed no serious adverse events or withdrawals due to treatment-emergent adverse events. The most common events were nasopharyngitis, coronavirus disease 2019, headache, fatigue, and diarrhea; fatigue and headache were the most frequent systemic reactions, and injection-site tenderness the most frequent local reaction. There were no substantial changes in allergen-specific immunoglobulin levels, basophil activation, or T helper cell subpopulations, and no difference in allergic clinical responses compared to placebo.

Conclusion

Intradermal DNA vaccine ASP2390 is safe and well tolerated but does not show an immunologic or clinical response in a small sample of adults allergic to HDM.

{"title":"Phase 1 study of safety, tolerability, and efficacy of intradermal DNA vaccine ASP2390 in adults allergic to house dust mites","authors":"Thomas Kayser MD, BS , Ronald Smulders MD, PhD , Tomohiro Kusawake PhD , Erik Wambre PhD , Gurunadh R. Chichili PhD , Mary B. Blauwet DrPH , Anna Spence MS , Melanie Patton BS , Rima Tabash PhD , Hannah A. DeBerg PhD , Sugandhika Khosa MS , Philipp Badorrek MD , Jens M. Hohlfeld MD , Brian C. Ferslew PharmD, PhD","doi":"10.1016/j.jacig.2025.100404","DOIUrl":"10.1016/j.jacig.2025.100404","url":null,"abstract":"<div><h3>Background</h3><div>House dust mite (HDM) allergies are prevalent, yet current treatments like allergen avoidance, pharmacotherapy, and conventional allergen immunotherapy present limitations. The novel LAMP (lysosomal-associated membrane protein)-based DNA vaccine ASP2390 targets major HDM allergens, potentially shifting immune responses toward nonallergic pathways and minimizing the risk of atopy, with positive safety and efficacy signals in preclinical models.</div></div><div><h3>Objective</h3><div>We evaluated the safety, tolerability, and efficacy of first-in-human intradermal ASP2390 in adults with HDM allergy.</div></div><div><h3>Methods</h3><div>A randomized, double-blind, placebo-controlled phase 1 trial was conducted in adults with HDM-induced allergic rhinitis. Participants received either 1 mg or 4 mg of ASP2390 or placebo intradermally once weekly for 12 weeks, with safety, tolerability, and pharmacodynamic responses assessed over a 63-week period, including early-phase clinical effects assessed via HDM exposure in an allergen challenge chamber.</div></div><div><h3>Results</h3><div>Twenty-eight adults (mean age, 26.9 years; 23 male participants), with 7 receiving 1 mg and 13 receiving 4 mg ASP2390, 8 receiving placebo, showed no serious adverse events or withdrawals due to treatment-emergent adverse events. The most common events were nasopharyngitis, coronavirus disease 2019, headache, fatigue, and diarrhea; fatigue and headache were the most frequent systemic reactions, and injection-site tenderness the most frequent local reaction. There were no substantial changes in allergen-specific immunoglobulin levels, basophil activation, or T helper cell subpopulations, and no difference in allergic clinical responses compared to placebo.</div></div><div><h3>Conclusion</h3><div>Intradermal DNA vaccine ASP2390 is safe and well tolerated but does not show an immunologic or clinical response in a small sample of adults allergic to HDM.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100404"},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143332861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical validity of dried blood spot assay for the measurement of functional C1 inhibitor in angioedema due to C1 inhibitor deficiency

The journal of allergy and clinical immunology. Global

Pub Date : 2025-01-07 DOI: 10.1016/j.jacig.2025.100401

Jonathan A. Bernstein MD , Jie Cheng PhD , Thomas Pisani MSc , Dan Sexton PhD , Rachel E. Whitaker PhD , Daniel Nova Estepan PharmD, RPh , Neil Inhaber MD

Background

Functional C1 inhibitor (fC1INH) is a key biomarker for the diagnosis of hereditary angioedema due to C1 inhibitor (C1INH) deficiency. A novel fC1INH assay from dried blood spot (DBS) reduces practical fC1INH testing limitations versus conventional fC1INH assays, but its sensitivity and specificity have not yet been characterized.

Objective

We sought to assess the sensitivity and specificity of fC1INH DBS assay and conventional fC1INH ELISA and chromogenic assay.

Methods

fC1INH DBS assay was performed in samples from 30 patients with previously diagnosed recurrent angioedema due to C1INH deficiency and from 100 healthy controls. Whole blood samples were spotted onto blotting paper and dried for 3 hours or longer, and then fC1INH from DBS was measured through its C1s protease inhibitory activity using liquid chromatography tandem mass spectrometry. fC1INH ELISA and chromogenic assays were performed by reanalyzing a subset of 29 patients and 50 healthy controls. Sensitivity and specificity were evaluated using a negative sample mean − 1.96 SD cutoff.

Results

fC1INH DBS assay had a sensitivity of 0.93, a specificity of 0.97, and area under the curve of the receiver-operating characteristic curve of 0.996 (95% CI, 0.989-1.000). In the subset, DBS and chromogenic assay had similar sensitivity (DBS, 1.00; chromogenic assay, 0.97) and specificity (DBS, 0.94; chromogenic assay, 1.00); ELISA sensitivity was lower (0.62) and specificity similar (1.00).

Conclusions

fC1INH DBS assay had similar sensitivity and specificity when contrasted with fC1INH chromogenic assay. Because of its easier sample collection and logistic benefits, fC1INH DBS assay may allow more accessible hereditary angioedema diagnostic testing, especially in underserved regions.

{"title":"Clinical validity of dried blood spot assay for the measurement of functional C1 inhibitor in angioedema due to C1 inhibitor deficiency","authors":"Jonathan A. Bernstein MD , Jie Cheng PhD , Thomas Pisani MSc , Dan Sexton PhD , Rachel E. Whitaker PhD , Daniel Nova Estepan PharmD, RPh , Neil Inhaber MD","doi":"10.1016/j.jacig.2025.100401","DOIUrl":"10.1016/j.jacig.2025.100401","url":null,"abstract":"<div><h3>Background</h3><div>Functional C1 inhibitor (fC1INH) is a key biomarker for the diagnosis of hereditary angioedema due to C1 inhibitor (C1INH) deficiency. A novel fC1INH assay from dried blood spot (DBS) reduces practical fC1INH testing limitations versus conventional fC1INH assays, but its sensitivity and specificity have not yet been characterized.</div></div><div><h3>Objective</h3><div>We sought to assess the sensitivity and specificity of fC1INH DBS assay and conventional fC1INH ELISA and chromogenic assay.</div></div><div><h3>Methods</h3><div>fC1INH DBS assay was performed in samples from 30 patients with previously diagnosed recurrent angioedema due to C1INH deficiency and from 100 healthy controls. Whole blood samples were spotted onto blotting paper and dried for 3 hours or longer, and then fC1INH from DBS was measured through its C1s protease inhibitory activity using liquid chromatography tandem mass spectrometry. fC1INH ELISA and chromogenic assays were performed by reanalyzing a subset of 29 patients and 50 healthy controls. Sensitivity and specificity were evaluated using a negative sample mean − 1.96 SD cutoff.</div></div><div><h3>Results</h3><div>fC1INH DBS assay had a sensitivity of 0.93, a specificity of 0.97, and area under the curve of the receiver-operating characteristic curve of 0.996 (95% CI, 0.989-1.000). In the subset, DBS and chromogenic assay had similar sensitivity (DBS, 1.00; chromogenic assay, 0.97) and specificity (DBS, 0.94; chromogenic assay, 1.00); ELISA sensitivity was lower (0.62) and specificity similar (1.00).</div></div><div><h3>Conclusions</h3><div>fC1INH DBS assay had similar sensitivity and specificity when contrasted with fC1INH chromogenic assay. Because of its easier sample collection and logistic benefits, fC1INH DBS assay may allow more accessible hereditary angioedema diagnostic testing, especially in underserved regions.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100401"},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A 33-year diagnostic odyssey in an Ashkenazi Jewish patient with Aicardi-Goutières syndrome

The journal of allergy and clinical immunology. Global

Pub Date : 2025-01-03 DOI: 10.1016/j.jacig.2025.100400

Oskar Schnappauf PhD , Hongying Wang PhD , Ivona Aksentijevich MD , Daniel L. Kastner MD, PhD , Ronald M. Laxer MD

The critical need for awareness and genetic testing of the SAMHD1 deletion in Ashkenazi Jewish patients is highlighted owing to its relatively high carrier frequency. Early detection can prevent severe disease complications through targeted therapy.

引用次数: 0

Acute/baseline ratios of all 3 MC mediator metabolites can enhance diagnosis and management of mast cell activation syndrome

The journal of allergy and clinical immunology. Global

Pub Date : 2024-12-28 DOI: 10.1016/j.jacig.2024.100399

Joseph H. Butterfield MD , Adela Taylor MD

Background

Mast cell (MC) activation syndrome (MCAS) can be a challenge to diagnose and treat despite the near continuous appearance of publications outlining specific criteria. Follow-up of the clinical responses to treatment is often lacking, and confirmation that leukotriene C₄ (LTC₄) is an active participant in MCAS has been overlooked.

Objective

Three patients with MCAS characterized by anaphylaxis are presented to illustrate (1) the value of contemporaneous urinary mediator sampling during MCAS in addition to serum tryptase measurements and (2) substantiation of the fact that not only can LTC₄ (measured metabolite LTE₄) be the highest metabolite measured, but (3) blockade of the LTE₄ receptor can contribute to symptom prevention.

Method

The study methods comprised clinical review and quantitation of acute and baseline levels of tryptase and urinary MC mediators.

Results

The cases of 3 patients with MCAS are reviewed. In the first case, vespid sting–induced anaphylaxis was associated with a marked increase in the LTE₄ excretion. The addition of montelukast was instituted, and subsequent stings did not evoke symptoms. In the second case, acute measurements showed substantial increased levels of (2,3-dinor)-11β-prostaglandin F_2α, and LTE₄. The addition of aspirin plus montelukast prevented subsequent attacks. The third case documents a perioperative anaphylactic event with an acute/baseline LTE₄ ratio far higher than those of tryptase or other metabolites.

Conclusions

The value of measuring all 3 MC mediator metabolites during MCAS should not be overlooked. These measurements can facilitate the successful prevention of attacks. Furthermore, results from these tests show that histamine is often a minor player, whereas acute/baseline levels of the metabolites of LTC₄ and prostaglandin D₂ are frequently much higher, warranting nonantihistamine treatment.

{"title":"Acute/baseline ratios of all 3 MC mediator metabolites can enhance diagnosis and management of mast cell activation syndrome","authors":"Joseph H. Butterfield MD , Adela Taylor MD","doi":"10.1016/j.jacig.2024.100399","DOIUrl":"10.1016/j.jacig.2024.100399","url":null,"abstract":"<div><h3>Background</h3><div>Mast cell (MC) activation syndrome (MCAS) can be a challenge to diagnose and treat despite the near continuous appearance of publications outlining specific criteria. Follow-up of the clinical responses to treatment is often lacking, and confirmation that leukotriene C<sub>4</sub> (LTC<sub>4</sub>) is an active participant in MCAS has been overlooked.</div></div><div><h3>Objective</h3><div>Three patients with MCAS characterized by anaphylaxis are presented to illustrate (1) the value of contemporaneous urinary mediator sampling during MCAS in addition to serum tryptase measurements and (2) substantiation of the fact that not only can LTC<sub>4</sub> (measured metabolite LTE<sub>4</sub>) be the highest metabolite measured, but (3) blockade of the LTE<sub>4</sub> receptor can contribute to symptom prevention.</div></div><div><h3>Method</h3><div>The study methods comprised clinical review and quantitation of acute and baseline levels of tryptase and urinary MC mediators.</div></div><div><h3>Results</h3><div>The cases of 3 patients with MCAS are reviewed. In the first case, vespid sting–induced anaphylaxis was associated with a marked increase in the LTE<sub>4</sub> excretion. The addition of montelukast was instituted, and subsequent stings did not evoke symptoms. In the second case, acute measurements showed substantial increased levels of (2,3-dinor)-11β-prostaglandin F<sub>2α</sub>, and LTE<sub>4</sub>. The addition of aspirin plus montelukast prevented subsequent attacks. The third case documents a perioperative anaphylactic event with an acute/baseline LTE<sub>4</sub> ratio far higher than those of tryptase or other metabolites.</div></div><div><h3>Conclusions</h3><div>The value of measuring all 3 MC mediator metabolites during MCAS should not be overlooked. These measurements can facilitate the successful prevention of attacks. Furthermore, results from these tests show that histamine is often a minor player, whereas acute/baseline levels of the metabolites of LTC<sub>4</sub> and prostaglandin D<sub>2</sub> are frequently much higher, warranting nonantihistamine treatment.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100399"},"PeriodicalIF":0.0,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tezepelumab treatment in severe asthma with recurrent chronic rhinosinusitis with nasal polyps: Case series

The journal of allergy and clinical immunology. Global

Pub Date : 2024-12-25 DOI: 10.1016/j.jacig.2024.100396

Yoshiro Kai MD, PhD

Background

Tezepelumab is a human IgG2 mAb that inhibits thymic stromal lymphopoietin (TSLP) and is approved for treatment of severe asthma. Bronchial asthma, usually a type 2 inflammatory disease, often co-occurs with chronic rhinosinusitis with nasal polyps (CRSwNP). However, tezepelumab has unknown effects on severe asthma with CRSwNP. Patients with CRSwNP are frequently candidates for endoscopic sinus surgery (ESS). CRSwNP is a crucial factor influencing asthma symptoms. However, some patients experience recurrent CRSwNP.

Objective

Tezepelumab was approved for use with CRSwNP, and TSLP is involved in the pathogenesis of CRSwNP. This study presents the cases of 2 patients with severe asthma complicated with recurrent CRSwNP after ESS in whom tezepelumab rapidly improved asthma and sinusitis symptoms.

Methods

We evaluated tezepelumab treatment in patients with severe asthma with recurrent CRSwNP based on symptoms, asthma exacerbation, level of type 2 cytokines, and lung function.

Results

After they had received a high-dose inhaled corticosteroid and long-acting β₂-agonist, the patients’ asthma remained uncontrolled, as defined by a low Asthma Control Test score. However, tezepelumab reduced severe asthma exacerbation, improved lung function, and controlled asthma symptoms. It improved CRSwNP, asthma-related symptoms, and exercise tolerance, and it inhibited type 2 cytokines extensively, indicating its effectiveness in treating CRSwNP. Tezepelumab was efficacious in these patients and improved their symptoms in terms of comorbidities of the upper and lower airways.

Conclusion

Tezepelumab was effective in treating asthma complicated with CRSwNP recurrence after ESS. However, further studies are required to identify the general and specific roles of tezepelumab in treating severe asthma and recurrent CRSwNP.

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引用次数: 0

Eosinophil ETosis and Charcot-Leyden crystals in Kimura disease

The journal of allergy and clinical immunology. Global

Pub Date : 2024-12-25 DOI: 10.1016/j.jacig.2024.100397

Yuzaburo Inoue MD, PhD , Hitoshi Ogata MD , Yoshitake Sato MD , Daigo Kato MD, PhD , Kanako Mitsunaga MD , Mamiko Saito MD, PhD , Tatsuya Ishigaki MD, PhD , Minako Tomiita MD, PhD , Hiroshi Kuraishi MD, PhD , Keisuke Ito DDS , Shigeharu Ueki MD, PhD

Two cases of refractory Kimura disease that required treatment with biologic agents are reported. Their pathology suggests the involvement of eosinophil ETosis, which is active cell death producing Charcot-Leyden crystals.

引用次数: 0

Correspondence re: Randhawa et al, TIP’s success in the treatment of cow’s milk anaphylaxis leaves many questions unanswered

The journal of allergy and clinical immunology. Global

Pub Date : 2024-12-24 DOI: 10.1016/j.jacig.2024.100394

Brian D. Modena MD, MSc , Allison Ramsey MD , Shahzad Mustafa MD , Doug Jones MD , Caroline Caperton MD, MSPH

引用次数: 0

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