Journal of Allergy and Clinical Immunology最新文献

{"title":"Understanding the childhood origins of asthma and COPD: insights from birth cohorts and studies across the lifespan.","authors":"Tina Hartert,Julie Nyholm Kvysgaard,Linesri Thaver,Aisha Suara-Istanbouli,James P Allinson,Heather J Zar","doi":"10.1016/j.jaci.2025.04.012","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.012","url":null,"abstract":"Birth cohorts have identified modifiable risk factors for asthma and respiratory health in children and adults, demonstrating the important role and pathways through which early life events influence not only child outcomes, but also adult health, disease and mortality. This is a focused literature update from 2021-2024 that summarizes birth cohort studies across the lifespan that contribute to our understanding of risk factors for and the childhood origins of asthma and COPD that may inform prevention efforts. We conclude that there are critical periods of developmental plasticity and susceptibility during which early life events and exposures likely have the greatest impact on the development of asthma and chronic obstructive lung disease phenotypes, and that there are important prenatal and early childhood exposures, which if modified, might be candidates for improving respiratory health across the lifespan. Birth cohorts have been and will continue to be critical to advancing our understanding of lung health and disease across the lifespan, including asthma and COPD. As child mortality declines and the human population ages, data from birth cohort studies are needed to inform strategies for optimizing healthy longevity, including the investment in understanding the lifelong consequences of adverse prenatal and early childhood exposures.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"1 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853083","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 Treatment Response Modified by PM2.5, NO2, and O3 Among African American Children: A Reanalysis of the AsthmaNet's BARD Trial.","authors":"Lizbeth F Gómez,Ellen Kinnee,Michael T Young,Joel D Kaufman,Anne M Fitzpatrick,Sharmilee M Nyenhuis,Julian Solway,Steven R White,Edward T Naureckas,Wanda Phipatanakul,Michael E Wechsler,Susan J Kunselman,David T Mauger,Leslie A McClure,Usama Bilal,Stephen C Lazarus,Fernando Holguin,Jane E Clougherty","doi":"10.1016/j.jaci.2025.04.009","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.009","url":null,"abstract":"BACKGROUNDAsthma morbidity significantly affects children of all racial backgrounds; however, African American children experience a greater disease burden than children from other racial groups. Despite the known influence of air pollution on asthma outcomes, its role in the efficacy of asthma treatments remains underexplored.OBJECTIVETo examine how exposure to particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) influenced treatment outcomes in the NIH AsthmaNet Best African American Response to Asthma Drugs (BARD) trial.METHODSThe BARD trial randomized 224 African American children to four asthma treatments consisting of inhaled corticosteroids (ICS) and long-acting beta antagonists (LABA) administered in a randomized crossover fashion. Treatment efficacy was assessed by the frequency of asthma exacerbations, percent predicted FEV1 (%PFEV1), and annualized asthma control days. Residential exposures to PM2.5, NO2, and O3 were estimated using a validated spatiotemporal model. Mixed effects models were used to evaluate the interaction between pollution exposure and treatment efficacy, adjusting for age, household triggers and trial site.RESULTSPM2.5, NO2, and O3 exposures ranged substantially across participants: from 2.28 - 15.3 μg/m3, 2.34 - 63.7 ppm, and 2.57 - 23.7 ppb, respectively. NO2 and PM2.5 exposures were not associated with increased exacerbations post-treatment (p for interaction = 0.15 and 0.08, respectively). However, NO2 exposure significantly modified the effect of high-dose ICS+LABA therapy on lung function. Children with below median NO2 exposures while on ICS + LABA had a reduction of 5.86 (1.16, 10.56) in %PFEV1 compared to those with above-median NO2 exposures.CONCLUSIONSResidential high NO2 exposure may significantly attenuate the efficacy of ICS+LABA therapy on lung function in African American children. These findings suggest the need to consider environmental factors in clinical trials and asthma management strategies.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"30 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849431","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":"Baseline basophil activation and early suppression is associated with clinical outcome after peanut sublingual immunotherapy.","authors":"Jessica R Humphrey,Rishu Guo,Xiaohong Yue,Corrine A Keet,Yamini V Virkud,J Andrew Bird,A Wesley Burks,Edwin H Kim,Johanna M Smeekens,Michael D Kulis","doi":"10.1016/j.jaci.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.010","url":null,"abstract":"BACKGROUNDSublingual immunotherapy (SLIT) was recently shown to safely induce desensitization and remission of peanut allergy in 1-to 4-year-old children.OBJECTIVEBasophil activation has been shown to be suppressed in allergen-specific immunotherapy. We aimed to evaluate the timing of basophil suppression during peanut SLIT and its impact on clinical outcomes.METHODSFifty peanut-allergic children were enrolled in a peanut SLIT trial and randomized to active peanut or placebo SLIT for 36 months followed by a three-month avoidance period to evaluate remission. Blood was collected at baseline, 12, 24, 36, and 39 months to measure basophil activation by CD63 and CD203c.RESULTSFor participants on peanut SLIT, basophil activation based on CD63 expression was significantly reduced by 12 months and continued to decrease throughout peanut SLIT, whereas CD63 activation in participants receiving placebo remained unchanged from 0-36 months. CD203c expression remained unchanged for both peanut SLIT and placebo participants throughout the trial. Actively treated participants who achieved remission had lower CD63 expression at baseline and significant suppression of CD63 expression by 12 months, while treatment failures had higher CD63 expression at baseline and lack of suppression by 12 months. Lower basophil activation in those achieving remission, compared to those that failed treatment, remained present for up to 3 years.CONCLUSIONSFollowing peanut SLIT, participants who achieved remission had significantly suppressed basophils by 12 months, compared to unsuccessful participants that were not desensitized, suggesting that early suppression of basophils may be indicative of peanut SLIT efficacy.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"27 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849470","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":"Innate immune reprogramming in circulating neutrophils of COPD patients.","authors":"Barbara Mariotti,Chiara Bracaglia,Sara Gasperini,Giulia Sartori,Ernesto Crisafulli,Flavia Bazzoni","doi":"10.1016/j.jaci.2025.04.011","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.011","url":null,"abstract":"BACKGROUNDChronic obstructive pulmonary disease (COPD) involves both local and systemic neutrophilic inflammation, with dysregulation in blood neutrophil numbers, frequencies, and functions.OBJECTIVETo characterize the transcriptional and epigenetic profiles of circulating neutrophils in COPD patients and explore correlations with neutrophil dysfunction and clinical disease parameters.METHODSCirculating neutrophils of COPD patients and control donors were subjected to RNA-sequencing (RNA-seq) and genome-wide analysis of histone 3 lysine 4 trimethylation (H3K4me3) by Chromatin Immunoprecipitation coupled with sequencing (ChIP-seq). Neutrophils' activation was assessed by cytofluorimetric analysis, O2- release and C. albicans phagocytosis assays.RESULTSRNA-seq and ChIP-seq analysis of H3K4me3 revealed a poised state in genes involved in innate immune activation, resembling the phenotype observed in neutrophils from BCG-vaccinated individuals, referred to as \"trained\", that is marked by weak or no expression under resting conditions but ready to be expressed at higher levels upon stimulation. The epigenetic signature identified in neutrophils from BCG-vaccinated subjects was enriched in COPD neutrophils. In particular, and consistent with what has been described in \"trained\" neutrophils, COPD neutrophils exhibited transcriptional reprogramming of metabolically relevant genes. Functionally, COPD neutrophils produced higher CXCL8 and IL-1β levels, released more O2-, and displayed greater phagocytic activity upon in vitro stimulation.CONCLUSIONThese findings suggest that COPD neutrophils undergo epigenetic, transcriptomic, and metabolic reprogramming, which enhances their responsiveness and aligns with the phenotype of neutrophils previously identified as \"trained\", offering mechanistic insight into the functional dysregulation observed in COPD.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"17 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846288","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":"Integrating Geospatial Data With Birth Cohorts to Explore Social Determinants of Health and Asthma.","authors":"Patrick H Ryan,Jeff Blossom,Cole Brokamp,Antonella Zanobetti,Diane R Gold","doi":"10.1016/j.jaci.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.001","url":null,"abstract":"Place-based measures of environmental exposures, climate, neighborhood characteristics, housing, and other social determinants of health (SDoH) are powerful predictors of health outcomes, including asthma. In addition, SDoH are likely causes of the persistent racial and ethnic disparities in asthma prevalence and morbidity. The objectives of this commentary are to 1) provide an overview of geospatial data and resources available to researchers to incorporate into studies of asthma-related outcomes, 2) provide a general approach to consider geospatial data in birth cohorts, 3) demonstrate the use of geospatial data in asthma-related research, and 4) highlight challenges and future opportunities for the use of geospatial data in asthma-related research and birth cohort studies. By integrating place-based data into longitudinal studies, researchers may identify critical drivers of asthma and asthma-related disparities and develop strategies to mitigate their impact.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"23 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831545","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":"Advancing birth cohort studies using administrative and other research-independent data repositories - opportunities and challenges.","authors":"Steven M Brunwasser,Allison K Warner,Christian Rosas Salazar,Pingsheng Wu","doi":"10.1016/j.jaci.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.002","url":null,"abstract":"The birth cohort study design is an essential epidemiological tool for investigating the developmental origins of health and disease. Birth cohorts have greatly improved the etiological understanding of asthma and allergic diseases, setting the stage for advancements in translational interventions. Increasingly, investigators leverage data repositories collected and maintained independently of research investigations (administrative data) to establish large birth cohorts or to augment data generated through active participant interaction. In many cases, administrative data can greatly enhance the capacity of birth cohorts to achieve their scientific goals. However, investigators must be wary of common pitfalls and carefully consider whether administrative data is well-suited to the scientific inquiry. This paper reviews the strengths and challenges of using administrative data and pragmatic solutions that have been developed to optimize their use in birth cohorts. As birth cohorts continue to play an important role in understanding early life disease etiology, unleashing the power of administrative data will greatly assist in this scientific process.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"13 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831666","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":"CAR therapies: development, design, and implementation.","authors":"Madeline J Lee,Frank Cichocki,Jeffrey S Miller","doi":"10.1016/j.jaci.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.005","url":null,"abstract":"Chimeric antigen receptor (CAR) T and NK cell therapies represent a promising strategy for the treatment of cancers and other chronic diseases. Engineered CAR constructs endow immune cells with the ability to target desired antigens with high specificity, allowing for directed responses to antigen-expressing cells. CAR T and NK cells have shown marked success in the treatment of hematological malignancies, although there remains a large population of patients that fail to respond to CAR therapies and their efficacy in solid tumors is still limited. In this review, we provide a broad overview of the development, design, and implementation of CAR therapies, from bench to bedside. We discuss the building blocks of CAR constructs and how these can be manipulated to optimize CAR functionality, review the possible sources of T and NK cells for CAR therapies, and examine the limitations of both CAR T and CAR NK cells. Finally, we discuss recent breakthroughs in the CAR field and consider how these advances may impact the success of CAR therapies in the years to come.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"90 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827109","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":"Effects of Inflammatory Endotypes on Disease Trajectory in Chronic Rhinosinusitis with Nasal Polyps.","authors":"Christina Dorismond,Yash Trivedi,Mason R Krysinski,Rory J Lubner,Li-Ching Huang,Sandeep Goswami,Quanhu Sheng,Rakesh K Chandra,Naweed I Chowdhury,Justin H Turner","doi":"10.1016/j.jaci.2025.03.029","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.03.029","url":null,"abstract":"BACKGROUNDWhile phenotypic features have traditionally guided treatment in chronic rhinosinusitis (CRS), recent research has favored categorization based on inflammatory endotype. However, the impact of endotypic differences on clinical outcomes remains largely unknown.OBJECTIVEWe aimed to compare disease trajectory, primarily time-to-polyp recurrence, between CRS with nasal polyp (CRSwNP) endotypes.METHODSSamples were obtained from CRSwNP patients undergoing surgery between 2015-2023, and cytokine levels were measured using a multiplex bead assay. Principal component analysis followed by hierarchical cluster analysis was used to identify endotype clusters. Clinical outcomes were subsequently compared between clusters RESULTS: We identified 6 CRSwNP disease clusters among the 269 included patients. Cluster 1 (46.5%) was characterized by relatively low inflammation. Clusters 4 (13.3%) and 6 (7.1%) also exhibited low inflammation but with elevated levels of interleukin (IL)-12/IL-21 and CCL5, respectively. Cluster 2 (4.5%) represented a mixed type 1/3 inflammatory endotype (IFN-γHigh/IL-4High/IL-17AHigh), and Cluster 3 (10.0%) was characterized by an innate, proinflammatory response (IL-1βHigh/IL-6High/IL-8High). Cluster 5 (18.9%) exhibited type 2 dominant inflammation (IL-5High/IL-9High/IL-13High). When comparing disease trajectory, Cluster 2 (IFN-γHigh/IL-4High/IL-17AHigh) and 4 (IL-12High/IL-21High) had the shortest time-to-polyp recurrence, while Cluster 3 (IL-1βHigh/IL-6High/IL-8High) demonstrated the longest time-to-recurrence (p<0.001). Time-to-oral steroids (p=0.13) and time-to-biologic therapy (p=0.43) were similar across clusters CONCLUSION: Our study highlights the heterogenous nature of CRSwNP and differences in disease trajectory between endotypes, notably that patients with mixed type 1 and 3 inflammation demonstrate more recalcitrant disease. These findings suggest that therapies beyond traditional type 2 inflammation treatments may be needed to effectively reduce CRSwNP disease recurrence.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"183 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827107","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":"A New Era for Complement Therapeutics.","authors":"Trent M Woodruff","doi":"10.1016/j.jaci.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.006","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"21 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827110","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":"Endotypes of Chronic Spontaneous Urticaria and Angioedema.","authors":"Dennis Wong,Susan Waserman,Gordon L Sussman","doi":"10.1016/j.jaci.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.004","url":null,"abstract":"The current understanding of chronic spontaneous urticaria (CSU) suggests that a complex network of inflammatory pathways is involved in its pathogenesis. Recent development highlighted autoimmunity as one of the key pathogenic mechanisms of CSU. Two endotypes, type I autoallergic (associated with IgE antibodies against autoantigens) and type IIb autoimmune (mediated by IgG autoantibodies against IgE or its high affinity receptor (FcεRI), have been characterized. A subpopulation of the patients has an overlap of the two endotypes. About 10% of patients with CSU presents with angioedema only. Patients with isolated mast-cell mediated angioedema have distinct clinical and demographic features and should be distinguished from bradykinin-mediated angioedema. Multiple potential biomarkers such as total IgE level and IgG anti-thyroid peroxidase have been identified, and together with the corresponding endotypes, have been linked to disease severity, duration and response to treatments. Currently, the utility of these biomarkers is limited in clinical settings given the few options of therapy. However, with the advent of novel treatments, endotyping CSU might help with tailoring treatment approach.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"6 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827112","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}