Journal of Allergy and Clinical Immunology最新文献

{"title":"An updated review of the use of omalizumab for the treatment of uncontrolled pediatric allergic asthma.","authors":"Bradley E Chipps, Meghan Farrell Garcia, Kevin R Murphy, Tmirah Haselkorn","doi":"10.1016/j.jaci.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.013","url":null,"abstract":"<p><p>Asthma has been increasingly recognized as a heterogeneous disease; however, many patients with asthma suffer from allergic asthma. While inhaled corticosteroids and other inhalers have been integral in treating many symptoms of asthma, these medications do not completely address the underlying mechanism of the disease. Pediatric asthma imposes a substantial burden on patients and the healthcare system. Omalizumab is consistently recognized as an important consideration for add-on therapy in pediatric patients with allergic asthma in published guidelines from multiple international societies such as the Global Initiative for Asthma. Since our last report in 2017, the amount of information available regarding the safety and effectiveness of omalizumab in pediatric patients with allergic asthma has continued to accumulate and is supported by several observational and real-world data studies. A number of studies including real-world effectiveness studies, post-hoc analyses of clinical trial data, and systematic literature reviews and meta-analyses have since expanded the published data on the efficacy and safety of omalizumab in pediatric patients. In this article, we present an updated review of this literature focused on use of omalizumab therapy in children with allergic asthma.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647278","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}

{"title":"COVID-19 in children: Evolving epidemiology, immunology, symptoms, diagnostics, treatment, post covid conditions, prevention strategies, and future directions.","authors":"Juliane Wurm, Nicole Ritz, Petra Zimmermann","doi":"10.1016/j.jaci.2024.11.012","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.012","url":null,"abstract":"<p><p>The epidemiology of COVID-19 in children has evolved throughout the pandemic, with initially low infection rates rising significantly due to the emergence of the more transmissible Omicron variant. Adolescents, children from ethnic minorities and lower-income households, and those with obesity are at increased risk of contracting SARS-CoV-2 infection. The immune response in children leads to milder symptoms compared to adults, with fever and cough being most frequent; tough symptoms vary by SARS-CoV-2 variant and age. Diagnostic methods to confirm current or past infection include RT-PCR, rapid antigen tests and serology. Treatment is mainly supportive, with antivirals and glucocorticoids reserved for severe cases. While serious conditions like MIS-C and other post-COVID-19 conditions are rare, they require careful management. Vaccination has proven effective in reducing severe disease and protecting against post-COVID-19 conditions. Continued surveillance, including wastewater monitoring and universal or pooled testing, remains crucial for controlling community spread. Key questions remain regarding the duration and quality of immunity following re-infection or vaccination, the impact of co-infections, and optimal treatment protocols for different pediatric populations.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647297","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}

{"title":"Anti-IgE therapy in chronic rhinosinusitis with nasal polyps.","authors":"Krishan D Chhiba, Gayatri B Patel, Anju T Peters","doi":"10.1016/j.jaci.2024.11.011","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.011","url":null,"abstract":"<p><p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition characterized by type 2 (T2) immune responses with significant impacts on quality of life and healthcare costs. Local IgE production in nasal polyp tissue plays a key role in the T2 inflammatory cascade. Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment for some patients with CRSwNP regardless of the patient's allergic status. Clinical trials, including pivotal POLYP 1 and POLYP 2 studies, demonstrated omalizumab's efficacy in reducing nasal polyp size, improving symptom scores, and enhancing quality of life, particularly in patients with comorbid asthma and aspirin-exacerbated respiratory disease (AERD). As we summarize in this review, omalizumab's effect appears to involve the reduction in local IgE and T2 inflammation; however, this remains poorly understood. Notably, omalizumab's effectiveness appears to be partially sustained after long-term use, though symptoms and inflammation begin to return upon discontinuation. Ongoing research is needed to determine the optimal duration of therapy and potential for biologics to modify the disease course. Additionally, further studies are needed to identify biomarkers to predict treatment response and to compare omalizumab with other biologics such as dupilumab, in head-to-head trials. Omalizumab is one of the key T2-targeted therapeutic options for CRSwNP with sustained effectiveness and strong safety profile.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647287","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}

{"title":"Making Sense of Adenosine Deaminase Variants and Their Clinical Implications.","authors":"Eyal Grunebaum, Robyn Loves, Donald B Kohn","doi":"10.1016/j.jaci.2024.11.010","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.010","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647309","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}

{"title":"The importance of mast cell histamine secretion in IgG-mediated systemic anaphylaxis.","authors":"Marat V Khodoun, Richard T Strait, Ashley Hall, Adrienne Stolfi, Fred D Finkelman","doi":"10.1016/j.jaci.2024.11.009","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.009","url":null,"abstract":"<p><strong>Background: </strong>IgG can mediate murine and human systemic anaphylaxis (SA). The roles of mast cells (MCs) and histamine in IgG-mediated anaphylaxis are controversial for mice and have not been studied in vivo for humans. We now investigate these issues.</p><p><strong>Methods: </strong>Actively or passively sensitized wild-type and immune-deficient mice were induced to develop anaphylaxis by i.v. antigen challenge. Anaphylaxis was characterized by evaluating hypothermia, hypomobility, histamine, and mast cell protease responses.</p><p><strong>Results: </strong>In contrast to our previous results with protein-immunized mice from a conventional colony, IgG-mediated passive SA in our SPF colony mice depended considerably on histamine produced by connective tissue MCs (CTMCs) in response to FcγRIII crosslinking. This was found for C57BL/6 and young male and female BALB/c mice, including BALB/c mice freshly arrived from 3 vendors. IgG-mediated anaphylaxis was less histamine-dependent in old than young mice. Although both mucosal MC (MMC) and CTMC responses were severely depleted in c-kit-deficient mice, MMC responses depended considerably more than CTMC responses on c-kit for maintenance. In immunologically naïve mice, FcγRIII crosslinking strongly activated a subset of CTMCs, but had little ability to activate MMCs. In vivo LPS + poly I.C treatment decreased histamine-dependence of IgG-mediated anaphylaxis while a strong Th2 immune response increased FcγRIII crosslinking-induced MMC activation. IgG-mediated activation of human MCs in reconstituted immunodeficient mice induced histamine-dependent anaphylaxis.</p><p><strong>Conclusion: </strong>IgG-dependent SA can be mediated largely by histamine released by mouse CTMCs and human MCs; histamine dependence is influenced by mouse age, sex, immune and infectious history, and the anaphylaxis model studied.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644188","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}

{"title":"BTK and MMP9 regulate NLRP3 inflammasome-dependent cytokine and NET responses in primary neutrophils.","authors":"Vinicius N C Leal, Francesca Bork, Maria Mateo Tortola, Juli-Christin von Guilleaume, Carsten L Greve, Stefanie Bugl, Bettina Danker, Bodo Grimbacher, Alessandra Pontillo, Alexander N R Weber","doi":"10.1016/j.jaci.2024.10.035","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.035","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is a double-edged state of immune activation required to resolve threats harmful to the host but can also cause severe collateral damage. Polymorphonuclear neutrophils (PMN) the primary leukocyte population in humans, mediate inflammation through the release of cytokines and neutrophil extracellular traps (NETs). Whilst the pathophysiological importance of NETs is unequivocal, the multiple molecular pathways driving NET release are not fully defined. Recently, NET release was linked to the NLRP3 inflammasome which is regulated by Bruton's tyrosine kinase in macrophages.</p><p><strong>Objective: </strong>As NLRP3 inflammasome regulation by BTK has not been studied in neutrophils, we here explored a potential regulatory role of BTK in primary murine and human neutrophils and matched monocytes or macrophages from Btk-deficient vs WT mice or healthy donors (HD) vs BTK-deficient X-linked agammaglobulinemia (XLA) patients, respectively.</p><p><strong>Methods: </strong>Cytokine, MPO and MMP-9 release were quantified by ELISA, NET release and inflammasome formation by immunofluorescence microscopy.</p><p><strong>Results: </strong>Surprisingly, in both mouse and human primary neutrophils, we observed a significant increase in NLRP3 inflammasome-dependent IL-1β and NETs when BTK was absent or inhibited, whereas IL-1β release was decreased in corresponding primary mouse macrophages or human PBMC, respectively. This suggests a novel negative regulatory role of BTK in terms of neutrophil NLRP3 activation. Both IL-1β and NET release in mouse and human primary neutrophils were strictly dependent of NLRP3, caspase-1 and, surprisingly, MMP-9.</p><p><strong>Conclusion: </strong>This highlights BTK and MMP-9 as novel and versatile inflammasome regulators and may have implications for the clinical use of BTK inhibitors.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638833","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}

{"title":"Early-life Upper Airway Microbiota are Associated with Decreased Lower Respiratory Tract Infections.","authors":"Susan Zelasko, Mary Hannah Swaney, Shelby Sandstrom, Kristine E Lee, Jonah Dixon, Colleen Riley, Lauren Watson, Jared J Godfrey, Naomi Ledrowski, Federico Rey, Nasia Safdar, Christine M Seroogy, James E Gern, Lindsay Kalan, Cameron Currie","doi":"10.1016/j.jaci.2024.11.008","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.008","url":null,"abstract":"<p><p>Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. To gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics, we sequenced and analyzed nasal (n=229) and oral (n=210) microbiomes with associated health/environmental data from our Wisconsin Infant Study Cohort at age 24-months. Participants with early-life lower respiratory tract infection (LRTI) were more likely to be formula-fed, attend daycare, and experience wheezing. Shotgun metagenomic sequencing with detection of viral and bacterial respiratory pathogens revealed nasal microbiome composition to associate with prior LRTI - namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M. catarrhalis, suggesting interbacterial competition impacts nasal pathogen colonization. This work advances understanding of protective host-microbial interactions occurring in airway microbiomes that alter infection susceptibility in early-life.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638887","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}

{"title":"Addressing health disparities in food allergy: A Position Statement of the AAAAI Prior Authorization Task Force.","authors":"","doi":"10.1016/j.jaci.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.008","url":null,"abstract":"<p><p>Self-reported food allergies (FAs) affect approximately 8% of the US pediatric and approximately 10% of the adult population, which reflects potentially disproportionate increases among ethnically and racially minoritized groups. Multiple gaps and unmet needs exist regarding FA disparities. There is reported evidence of disparities in FA outcomes, and the FA burden may also be disproportionate in low-income families. Low family income has been associated with higher emergency care spending and insecure access to allergen-free food. Pharmacoinequity arises in part as a result of structural racism still experienced by historically marginalized populations today. Historically redlined communities continue to experience greater rates of neighborhood-level air pollution and indoor allergen exposure, lack of transportation to medical appointments, poverty, and lower prescription rates of necessary medications. Clinical research needs racially and ethnically diverse participation to ensure generalizability of research findings and equitable access to medical advances, but race reporting in clinical trials has been historically poor. Addressing health disparities in FA is a priority of clinical care, with professional organizations such as the American Academy of Allergy, Asthma & Immunology having a prominent role to play in mitigating the challenges faced by these individuals. In this position statement we recommend some key steps to address this important issue.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638831","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}

{"title":"Developmental trajectories of atopic dermatitis with multi-omics approaches in the infant gut: COCOA birth cohort.","authors":"Eun Lee, Jeong-Hyun Kim, So-Yeon Lee, Si Hyeon Lee, Yoon Mee Park, Hea Young Oh, Jeonghun Yeom, Hee-Sung Ahn, Hyun Ju Yoo, Bong-Soo Kim, Sun Mi Yun, Eom Ji Choi, Kun Baek Song, Min Jee Park, Kangmo Ahn, Kyung Won Kim, Youn Ho Shin, Dong In Suh, Joo Young Song, Soo-Jong Hong","doi":"10.1016/j.jaci.2024.10.036","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.036","url":null,"abstract":"<p><strong>Background: </strong>An understanding of the phenotypes and endotypes of atopic dermatitis (AD) is essential for developing precision therapies. Recent studies have demonstrated evidence for the gut-skin axis in AD.</p><p><strong>Objective: </strong>To determine the natural course and clinical characteristics of AD phenotypes and investigate their mechanisms based on multi-omics analyses.</p><p><strong>Methods: </strong>Latent class trajectory analysis was used to AD phenotype in 2247 children who were followed until 9 years of age from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA) birth cohort study. Multi-omics analyses (microbiome, metabolites, and gut epithelial cell transcriptome) using stool samples collected at 6 months of age were performed to elucidate the underlying mechanisms of AD phenotypes.</p><p><strong>Results: </strong>Five AD phenotypes were classified as follows: never/infrequent, early-onset transient, intermediate-transient, late-onset, and early-onset persistent. Early-onset persistent and late-onset phenotypes showed increased risks of food allergy and wheezing treatment ever, with bronchial hyperresponsiveness only evident in the early-onset persistent phenotype. Multi-omics analyses revealed a significantly lower relative abundance of Ruminococcus gnavus and a decreased gut acetate level in the early-onset persistent phenotype, with potential associations to ACSS2, JAK-STAT signaling, and systemic Th2 inflammation. The early-onset transient phenotype was associated with AMPK and/or chemokine signaling regulation, whereas the late-onset phenotype was linked with IL-17 and barrier dysfunction.</p><p><strong>Conclusions: </strong>Multi-omics profiling in early life may offer insights into different mechanisms underlying AD phenotypes in children.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638883","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}

{"title":"Asthma and Respiratory Co-Morbidities.","authors":"Dennis K Ledford, Tae-Bum Kim, Victor E Ortega, Juan Carlos Cardet","doi":"10.1016/j.jaci.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.006","url":null,"abstract":"<p><p>Asthma is a common respiratory condition with various phenotypes, non-specific symptoms and variable clinical course. The occurrence of other respiratory conditions with asthma, respiratory co-morbidities (RCs), is not unusual. A literature search was performed for asthma and a variety of respiratory co-morbidities using Pub-Med for the years 2019-2024. The 5 conditions with the largest number of references, other than rhinitis and rhinosinusitis addressed in another paper in this issue, or which are the most problematic in the authors' clinical experience are summarized. Others are briefly discussed. The diagnosis and treatment of both asthma and RCs are complicated by the overlap of symptoms and signs. Recognizing RCs is especially problematic in adult onset, non-type 2 asthma as there are no biomarkers to assist in confirming non-type 2 asthma. Treatment decisions in subjects with suspected asthma and RCs are complicated by the potential similarities between the symptoms or signs of the RC and asthma, the absence of a sine quo non for the diagnosis of asthma, the likelihood that many RCs improve with systemic corticosteroids, and the possibility that the manifestations of the RCs are misattributed to asthma or vice versa. Recognition of RCs is critical to the effective management of asthma, particularly severe or difficult to treat asthma.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620965","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}