Pub Date : 2025-04-24DOI: 10.1016/j.jaci.2025.03.026
Yannis Hadjiyannis,Madison N Martinez,Joseph Pechacek,Ibrahim Abukhiran,Deanna Riley,Stefania Pittaluga,Elena M Morariu,Michail S Lionakis,David G Binion,Reed Van Deusen
{"title":"Selective JAK1 inhibition remits multiorgan autoimmunity in a patient with refractory autoimmune polyendocrine syndrome type 1.","authors":"Yannis Hadjiyannis,Madison N Martinez,Joseph Pechacek,Ibrahim Abukhiran,Deanna Riley,Stefania Pittaluga,Elena M Morariu,Michail S Lionakis,David G Binion,Reed Van Deusen","doi":"10.1016/j.jaci.2025.03.026","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.03.026","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"1 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872022","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 : 2025-04-23DOI: 10.1016/j.jaci.2024.12.1086
Dave Singh,MeiLan K Han,Jean-Pierre Llanos,Neil Martin,Amit Parulekar,Konstantinos Kostikas,Sandhia S Ponnarambil
{"title":"Clarification of the efficacy of tezepelumab in the phase 2a COURSE trial.","authors":"Dave Singh,MeiLan K Han,Jean-Pierre Llanos,Neil Martin,Amit Parulekar,Konstantinos Kostikas,Sandhia S Ponnarambil","doi":"10.1016/j.jaci.2024.12.1086","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1086","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"32 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866831","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 : 2025-04-21DOI: 10.1016/j.jaci.2025.03.022
Jean Bousquet,Josep M Anto,Tari Haahtela,Bernardo Sousa-Pinto,Mario Morais-Almeida
{"title":"From \"one airway, one disease\" to \"one airway, many diseases\".","authors":"Jean Bousquet,Josep M Anto,Tari Haahtela,Bernardo Sousa-Pinto,Mario Morais-Almeida","doi":"10.1016/j.jaci.2025.03.022","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.03.022","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"53 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866391","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 : 2025-04-21DOI: 10.1016/j.jaci.2025.04.015
Andrea Apter,Tina Hartert
{"title":"Harnessing birth cohorts to decode asthma.","authors":"Andrea Apter,Tina Hartert","doi":"10.1016/j.jaci.2025.04.015","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.015","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"69 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872096","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 : 2025-04-18DOI: 10.1016/j.jaci.2025.01.048
Tolly E G Epstein,Andrew C Rorie,German D Ramon,Anjeni Keswani,Jonathan Bernstein,Rosa Codina,Christopher Codispoti,Timothy Craig,Mark Dykewicz,Denisa Ferastraoaru,Daniel Katz,Jean Kim,Désirée Larenas-Linnemann,Anil Nanda,Anh Nguyen,Mahesh Padukudru Anand,Amber Patterson,Punita Ponda,Elina Toskala,Anita N Wasan
Climate change is imposing a profound effect on health conditions triggered by environmental exposures. Climate change has affected aeroallergens in numerous ways, including: (1) changes in the vegetation microbiome distribution, (2) increases in C4 grasses globally, (3) increased occurrence of acute weather events, (4) increases in ambient temperature that amplify fungal spore concentration and pollen season duration, and (5) increased allergenicity of pollen and fungi due to exposure to higher levels of carbon dioxide, ozone, and diesel exhaust particles. In addition, greenhouse gases and air pollutants disrupt the epithelial barrier, trigger eosinophilic inflammation, and serve as adjuvants that stimulate IgE-mediated responses. All of these factors have influenced the prevalence and morbidity of allergic rhinitis, nonallergic rhinitis, and chronic rhinosinusitis. Data regarding changes in aeroallergen exposures due to climate change are lacking, and longitudinal sensitization data are rarely available. Allergists need to adapt diagnostic and treatment strategies to limit aeroallergen and air pollutant exposure and facilitate desensitization. Steps needed to address these challenges include: (1) expanding local measurement of pollen and fungal spores, (2) increasing the intensity of allergen avoidance measures, (3) addressing supply chain issues, and (4) promoting collaboration between allergists, insurance companies, aeroallergen manufacturers, and regulatory agencies.
{"title":"Impact of climate change on aerobiology, rhinitis, and allergen immunotherapy: Work Group Report from the Aerobiology, Rhinitis, Rhinosinusitis & Ocular Allergy, and Immunotherapy, Allergen Standardization & Allergy Diagnostics Committees of the American Academy of Allergy, Asthma & Immunology.","authors":"Tolly E G Epstein,Andrew C Rorie,German D Ramon,Anjeni Keswani,Jonathan Bernstein,Rosa Codina,Christopher Codispoti,Timothy Craig,Mark Dykewicz,Denisa Ferastraoaru,Daniel Katz,Jean Kim,Désirée Larenas-Linnemann,Anil Nanda,Anh Nguyen,Mahesh Padukudru Anand,Amber Patterson,Punita Ponda,Elina Toskala,Anita N Wasan","doi":"10.1016/j.jaci.2025.01.048","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.048","url":null,"abstract":"Climate change is imposing a profound effect on health conditions triggered by environmental exposures. Climate change has affected aeroallergens in numerous ways, including: (1) changes in the vegetation microbiome distribution, (2) increases in C4 grasses globally, (3) increased occurrence of acute weather events, (4) increases in ambient temperature that amplify fungal spore concentration and pollen season duration, and (5) increased allergenicity of pollen and fungi due to exposure to higher levels of carbon dioxide, ozone, and diesel exhaust particles. In addition, greenhouse gases and air pollutants disrupt the epithelial barrier, trigger eosinophilic inflammation, and serve as adjuvants that stimulate IgE-mediated responses. All of these factors have influenced the prevalence and morbidity of allergic rhinitis, nonallergic rhinitis, and chronic rhinosinusitis. Data regarding changes in aeroallergen exposures due to climate change are lacking, and longitudinal sensitization data are rarely available. Allergists need to adapt diagnostic and treatment strategies to limit aeroallergen and air pollutant exposure and facilitate desensitization. Steps needed to address these challenges include: (1) expanding local measurement of pollen and fungal spores, (2) increasing the intensity of allergen avoidance measures, (3) addressing supply chain issues, and (4) promoting collaboration between allergists, insurance companies, aeroallergen manufacturers, and regulatory agencies.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"1 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853079","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 : 2025-04-17DOI: 10.1016/j.jaci.2025.04.012
Tina Hartert,Julie Nyholm Kvysgaard,Linesri Thaver,Aisha Suara-Istanbouli,James P Allinson,Heather J Zar
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.
{"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}
Pub Date : 2025-04-15DOI: 10.1016/j.jaci.2025.04.009
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
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.
{"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}
Pub Date : 2025-04-15DOI: 10.1016/j.jaci.2025.04.010
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
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.
{"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}
Pub Date : 2025-04-14DOI: 10.1016/j.jaci.2025.04.011
Barbara Mariotti,Chiara Bracaglia,Sara Gasperini,Giulia Sartori,Ernesto Crisafulli,Flavia Bazzoni
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.
{"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}
Pub Date : 2025-04-11DOI: 10.1016/j.jaci.2025.04.001
Patrick H Ryan,Jeff Blossom,Cole Brokamp,Antonella Zanobetti,Diane R Gold
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.
{"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}
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