{"title":"What Is the Next Step for Patients With Aspirin‐Exacerbated Respiratory Disease: Biologics With or Without Aspirin Therapy?","authors":"Piotr Szatkowski, Lucyna Mastalerz","doi":"10.1111/all.16462","DOIUrl":"https://doi.org/10.1111/all.16462","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"20 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908222","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}
Rahul Sharma, Kaiyuan Wu, Kim Han, Anna Chiara Russo, Pradeep K Dagur, Christian A Combs, Xianglan Yao, Stewart J Levine, Michael N Sack
Background: The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4+ T cells may further advance our understanding of regulatory events linked to mitochondrial and/or endolysosomal function in adaptive immunity.
Methods: CD4+ T cells were analyzed from control and CD4+ T-cell-specific BLOC1S1 knockout mice. Polarization profiles were assayed using biochemical and molecular signatures, and signaling pathways were disrupted pharmacologically or via siRNA. Mouse models of airway and skin inflammation were generated by Ovalbumin and MC903 exposure, respectively.
Results: TH2 regulator GATA3 and phosphorylated STAT6 were preferentially induced in BLOC1S1-depleted primary CD4+ T (TKO) cells. The levels of IL-4, IL-5, and IL-13 were markedly induced in the absence of BLOC1S1. At the organelle level, mitochondrial DNA leakage evoked cGAS-STING and NF-κB pathway activation with subsequent TH2 polarization. The induction of autophagy with rapamycin reduced cytosolic mtDNA and reversed these TH2 signatures. Furthermore, genetic knockdown of STING and NF-κB inhibition ameliorated this immune regulatory cascade in TKO cells. Finally, at a functional level, TKO mice displayed an increased susceptibility to allergic conditions, including dermatitis and allergic asthma.
Conclusions: BLOC1S1 depletion in mouse CD4+ T cells mediated disruption of mitochondrial integrity to initiate a predominant TH2-responsive phenotype via STING-NF-κB-driven signaling of the canonical TH2 regulatory program.
{"title":"BLOC1S1 Control of Vacuolar Organelle Fidelity Modulates Murine T<sub>H</sub>2 Cell Immunity and Allergy Susceptibility.","authors":"Rahul Sharma, Kaiyuan Wu, Kim Han, Anna Chiara Russo, Pradeep K Dagur, Christian A Combs, Xianglan Yao, Stewart J Levine, Michael N Sack","doi":"10.1111/all.16461","DOIUrl":"10.1111/all.16461","url":null,"abstract":"<p><strong>Background: </strong>The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4<sup>+</sup> T cells may further advance our understanding of regulatory events linked to mitochondrial and/or endolysosomal function in adaptive immunity.</p><p><strong>Methods: </strong>CD4<sup>+</sup> T cells were analyzed from control and CD4<sup>+</sup> T-cell-specific BLOC1S1 knockout mice. Polarization profiles were assayed using biochemical and molecular signatures, and signaling pathways were disrupted pharmacologically or via siRNA. Mouse models of airway and skin inflammation were generated by Ovalbumin and MC903 exposure, respectively.</p><p><strong>Results: </strong>T<sub>H</sub>2 regulator GATA3 and phosphorylated STAT6 were preferentially induced in BLOC1S1-depleted primary CD4<sup>+</sup> T (TKO) cells. The levels of IL-4, IL-5, and IL-13 were markedly induced in the absence of BLOC1S1. At the organelle level, mitochondrial DNA leakage evoked cGAS-STING and NF-κB pathway activation with subsequent T<sub>H</sub>2 polarization. The induction of autophagy with rapamycin reduced cytosolic mtDNA and reversed these T<sub>H</sub>2 signatures. Furthermore, genetic knockdown of STING and NF-κB inhibition ameliorated this immune regulatory cascade in TKO cells. Finally, at a functional level, TKO mice displayed an increased susceptibility to allergic conditions, including dermatitis and allergic asthma.</p><p><strong>Conclusions: </strong>BLOC1S1 depletion in mouse CD4<sup>+</sup> T cells mediated disruption of mitochondrial integrity to initiate a predominant T<sub>H</sub>2-responsive phenotype via STING-NF-κB-driven signaling of the canonical T<sub>H</sub>2 regulatory program.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906370","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}
Deniz Eyice Karabacak, Lisa Arzt-Gradwohl, Barbara Binder, Eva Schadelbauer, Christina Vallant, Karin Laipold, Gunter J Sturm
{"title":"Soybean Oil in Propofol Is Not Able to Induce Allergic Reactions.","authors":"Deniz Eyice Karabacak, Lisa Arzt-Gradwohl, Barbara Binder, Eva Schadelbauer, Christina Vallant, Karin Laipold, Gunter J Sturm","doi":"10.1111/all.16454","DOIUrl":"https://doi.org/10.1111/all.16454","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902517","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}
Virginie Doyen,Nicolas Migueres,Vera van Kampen,Hille Suojalehto,Paola Mason,Xavier Munoz,Joaquin Sastre,Santiago Quirce,Cecilie Svanes,Gareth Walters,Vicky Moore,Iben Brock Jacobsen,Ilenia Folletti,Alexandra M Preiser,Jolanta Walusiak-Skorupa,Catherine Rifflart,Frédéric de Blay,Olivier Vandenplas,
BACKGROUNDExposure-related changes in exhaled nitric oxide (FeNO) and sputum eosinophils have not been thoroughly compared in the investigation of occupational asthma.OBJECTIVEThis study aimed at comparing the accuracies of the changes in FeNO concentrations and sputum eosinophil counts in identifying asthmatic reactions induced by occupational agents during specific inhalation challenges (SICs).METHODSThis retrospective multicenter study included 321 subjects who completed an assessment of FeNO and sputum eosinophils before and 24 h after SICs with various occupational agents, of whom 156 showed a positive result.RESULTSPost-challenge changes in FeNO and sputum eosinophils showed similar accuracies, with areas under the receiver operating characteristics curve of 0.78 (95% confidence interval [95% CI], 0.72-0.83) and 0.81 (95% CI, 0.76-0.86), respectively. Increases in FeNO level ≥ 13 ppb and sputum eosinophils ≥ 1.25% were identified as the optimal threshold values for differentiating positive from negative SICs. Using these thresholds, the changes in FeNO and sputum eosinophils each achieved a ≥ 95% specificity but a low sensitivity (55% and 62%, respectively). FeNO and sputum eosinophils showed discordant increases in 38% of subjects with a positive SIC. Combining either a rise in FeNO ≥ 13 ppb or an increase in sputum eosinophils ≥ 1.25% increased the sensitivity to 77%.CONCLUSIONSIncreases in FeNO concentration and/or sputum eosinophils after exposure to occupational agents strongly support a diagnosis of occupational asthma. The assessment of both markers of airway inflammation should be regarded as a reliable complementary tool to spirometry for identifying bronchial responses to occupational agents.
{"title":"Exhaled Nitric Oxide and Sputum Eosinophils Are Complementary Tools for Diagnosing Occupational Asthma.","authors":"Virginie Doyen,Nicolas Migueres,Vera van Kampen,Hille Suojalehto,Paola Mason,Xavier Munoz,Joaquin Sastre,Santiago Quirce,Cecilie Svanes,Gareth Walters,Vicky Moore,Iben Brock Jacobsen,Ilenia Folletti,Alexandra M Preiser,Jolanta Walusiak-Skorupa,Catherine Rifflart,Frédéric de Blay,Olivier Vandenplas,","doi":"10.1111/all.16447","DOIUrl":"https://doi.org/10.1111/all.16447","url":null,"abstract":"BACKGROUNDExposure-related changes in exhaled nitric oxide (FeNO) and sputum eosinophils have not been thoroughly compared in the investigation of occupational asthma.OBJECTIVEThis study aimed at comparing the accuracies of the changes in FeNO concentrations and sputum eosinophil counts in identifying asthmatic reactions induced by occupational agents during specific inhalation challenges (SICs).METHODSThis retrospective multicenter study included 321 subjects who completed an assessment of FeNO and sputum eosinophils before and 24 h after SICs with various occupational agents, of whom 156 showed a positive result.RESULTSPost-challenge changes in FeNO and sputum eosinophils showed similar accuracies, with areas under the receiver operating characteristics curve of 0.78 (95% confidence interval [95% CI], 0.72-0.83) and 0.81 (95% CI, 0.76-0.86), respectively. Increases in FeNO level ≥ 13 ppb and sputum eosinophils ≥ 1.25% were identified as the optimal threshold values for differentiating positive from negative SICs. Using these thresholds, the changes in FeNO and sputum eosinophils each achieved a ≥ 95% specificity but a low sensitivity (55% and 62%, respectively). FeNO and sputum eosinophils showed discordant increases in 38% of subjects with a positive SIC. Combining either a rise in FeNO ≥ 13 ppb or an increase in sputum eosinophils ≥ 1.25% increased the sensitivity to 77%.CONCLUSIONSIncreases in FeNO concentration and/or sputum eosinophils after exposure to occupational agents strongly support a diagnosis of occupational asthma. The assessment of both markers of airway inflammation should be regarded as a reliable complementary tool to spirometry for identifying bronchial responses to occupational agents.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"148 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887544","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}
Agnes Sze‐Yin Leung, Yuhan Xing, Montserrat Fernández‐Rivas, Gary Wing‐Kin Wong
Food allergies are increasing globally, particularly in Asia; however, the etiologies of allergic diseases remain poorly understood despite comprehensive studies conducted across a variety of populations. Epidemiological research demonstrates that food allergy is more prevalent in Westernized or urbanized societies than in rural or developing ones. As such, comparing the distribution and patterns of food allergies as well as the environmental exposures between regions may provide insight into potential causal and protective factors of food allergy. Diet is an important exposome that has been shown to modulate the immune system both directly and indirectly via pathways involving the microbiota. Changes in dietary patterns, especially the shift to a Westernized diet with reduced dietary fiber and an abundance of processed foods, impact the gut and skin epithelial barrier and contribute to the development of chronic inflammatory diseases, such as food allergy. Although dietary intervention is believed to have tremendous potential as a strategy to promote immunological health, it is essential to recognize that diet is only one of many factors that have changed in urbanized societies. Other factors, such as pollution, microplastics, the use of medications like antibiotics, and exposure to biodiversity and animals, may also play significant roles, and further research is needed to determine which exposures are most critical for the development of food allergies.
{"title":"The Relationship Between Dietary Patterns and the Epidemiology of Food Allergy","authors":"Agnes Sze‐Yin Leung, Yuhan Xing, Montserrat Fernández‐Rivas, Gary Wing‐Kin Wong","doi":"10.1111/all.16455","DOIUrl":"https://doi.org/10.1111/all.16455","url":null,"abstract":"Food allergies are increasing globally, particularly in Asia; however, the etiologies of allergic diseases remain poorly understood despite comprehensive studies conducted across a variety of populations. Epidemiological research demonstrates that food allergy is more prevalent in Westernized or urbanized societies than in rural or developing ones. As such, comparing the distribution and patterns of food allergies as well as the environmental exposures between regions may provide insight into potential causal and protective factors of food allergy. Diet is an important exposome that has been shown to modulate the immune system both directly and indirectly via pathways involving the microbiota. Changes in dietary patterns, especially the shift to a Westernized diet with reduced dietary fiber and an abundance of processed foods, impact the gut and skin epithelial barrier and contribute to the development of chronic inflammatory diseases, such as food allergy. Although dietary intervention is believed to have tremendous potential as a strategy to promote immunological health, it is essential to recognize that diet is only one of many factors that have changed in urbanized societies. Other factors, such as pollution, microplastics, the use of medications like antibiotics, and exposure to biodiversity and animals, may also play significant roles, and further research is needed to determine which exposures are most critical for the development of food allergies.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"29 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886903","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}
Elise M. A. Slob, Susanne J. H. Vijverberg, Tom Ruffles, Lieke C. E. Noij, Jacqueline Biermann, Alwin F. J. Brouwer, Kristel van den Brink, Annette de Bruin‐Kok, Bart E. Van Ewijk, Eric Haarman, Sanne C. Hammer, Simone Hashimoto, Fiona Hogarth, Christina J. Jones, Arvid W. A. Kamps, Elin T. G. Kersten, Ismé de Kleer, Brian J. Lipworth, Roberta Littleford, Marieke Mérelle, Alexander Moeller, Colin N. A. Palmer, Kristina Pilvinyte, Niels W. Rutjes, Ron H. N. van Schaik, Helen E. Smith, Roger Tavendale, Suzanne W. J. Terheggen‐Lagro, Steve Turner, Jos W. R. Twisk, Anja Vaessen‐Verberne, Mariël Verwaal, Tjalling de Vries, Judit Wesseling, Mariëlle W. Pijnenburg, Gerard H. Koppelman, Somnath Mukhopadhyay, Anke H. Maitland‐van der Zee
BackgroundLong‐acting beta2‐agonists (LABA) in combination with inhaled corticosteroids (ICS) are commonly used to treat asthma, however, some children lack response to the addition of LABA. This might be partially due to the presence of the Arg16Gly polymorphism, encoded by rs1042713 G>A in the ADRB2 gene. Carrying the A allele (Arg16) at this variant has been associated with an increased risk of exacerbations despite LABA treatment. We investigated whether genotype‐guided treatment improved asthma‐related outcomes.MethodsWe conducted an individual participant data meta‐analysis of two randomised controlled trials: PUFFIN (Dutch and Swiss 6–18 year‐olds) and PACT (English and Scottish 12–18 year‐olds). Children with uncontrolled asthma despite ICS who required a step‐up in treatment were included. Participants were randomised to genotype‐guided treatment or the control group with a follow‐up of at least 6 months. Genotype‐guided treatment consisted of adding LABA for children with ADRB2 Gly16/Gly16, whilst children with ADRB2 Arg16/Arg16 or Arg16/Gly16 were treated with double dose ICS (PUFFIN) or add‐on montelukast (PACT). The primary outcome was a change in asthma control; secondary outcomes included exacerbation rate and time to exacerbation. Repeated measures mixed models and Cox regression were used.ResultsFifty‐nine out of 102 (PUFFIN) and 59 out of 91 (PACT) children had at least one Arg (A allele). Amongst all 193 children, no difference was observed in asthma control between the study groups. However, genotype‐guided treatment resulted in lower asthma exacerbation rates (−0.08 (95%CI −0.16 to −0.00, p = 0.04)) compared to the control group.ConclusionGenotype‐guided step‐up treatment for children with uncontrolled asthma on ICS may lower asthma exacerbation rates and may be useful for personalising asthma care.
{"title":"Genotype‐Guided Asthma Treatment Reduces Exacerbations in Children: Meta‐Analysis of Two RCTs","authors":"Elise M. A. Slob, Susanne J. H. Vijverberg, Tom Ruffles, Lieke C. E. Noij, Jacqueline Biermann, Alwin F. J. Brouwer, Kristel van den Brink, Annette de Bruin‐Kok, Bart E. Van Ewijk, Eric Haarman, Sanne C. Hammer, Simone Hashimoto, Fiona Hogarth, Christina J. Jones, Arvid W. A. Kamps, Elin T. G. Kersten, Ismé de Kleer, Brian J. Lipworth, Roberta Littleford, Marieke Mérelle, Alexander Moeller, Colin N. A. Palmer, Kristina Pilvinyte, Niels W. Rutjes, Ron H. N. van Schaik, Helen E. Smith, Roger Tavendale, Suzanne W. J. Terheggen‐Lagro, Steve Turner, Jos W. R. Twisk, Anja Vaessen‐Verberne, Mariël Verwaal, Tjalling de Vries, Judit Wesseling, Mariëlle W. Pijnenburg, Gerard H. Koppelman, Somnath Mukhopadhyay, Anke H. Maitland‐van der Zee","doi":"10.1111/all.16438","DOIUrl":"https://doi.org/10.1111/all.16438","url":null,"abstract":"BackgroundLong‐acting beta2‐agonists (LABA) in combination with inhaled corticosteroids (ICS) are commonly used to treat asthma, however, some children lack response to the addition of LABA. This might be partially due to the presence of the Arg16Gly polymorphism, encoded by rs1042713 G>A in the <jats:italic>ADRB2</jats:italic> gene. Carrying the A allele (Arg16) at this variant has been associated with an increased risk of exacerbations despite LABA treatment. We investigated whether genotype‐guided treatment improved asthma‐related outcomes.MethodsWe conducted an individual participant data meta‐analysis of two randomised controlled trials: PUFFIN (Dutch and Swiss 6–18 year‐olds) and PACT (English and Scottish 12–18 year‐olds). Children with uncontrolled asthma despite ICS who required a step‐up in treatment were included. Participants were randomised to genotype‐guided treatment or the control group with a follow‐up of at least 6 months. Genotype‐guided treatment consisted of adding LABA for children with <jats:italic>ADRB2</jats:italic> Gly16/Gly16, whilst children with <jats:italic>ADRB2</jats:italic> Arg16/Arg16 or Arg16/Gly16 were treated with double dose ICS (PUFFIN) or add‐on montelukast (PACT). The primary outcome was a change in asthma control; secondary outcomes included exacerbation rate and time to exacerbation. Repeated measures mixed models and Cox regression were used.ResultsFifty‐nine out of 102 (PUFFIN) and 59 out of 91 (PACT) children had at least one Arg (A allele). Amongst all 193 children, no difference was observed in asthma control between the study groups. However, genotype‐guided treatment resulted in lower asthma exacerbation rates (−0.08 (95%CI −0.16 to −0.00, <jats:italic>p</jats:italic> = 0.04)) compared to the control group.ConclusionGenotype‐guided step‐up treatment for children with uncontrolled asthma on ICS may lower asthma exacerbation rates and may be useful for personalising asthma care.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"32 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886907","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}
Emilie Pacheco Da Silva, Tobias Weinmann, Jessica Gerlich, Gudrun Weinmayr, Jon Genuneit, Dennis Nowak, Erika von Mutius, Christian Vogelberg, Katja Radon, Felix Forster
BackgroundUsing disinfectants and cleaning products (DCPs) at home and work is known to influence both the onset and course of asthma, but most epidemiological studies did not consider the multiplicity and correlations of exposures to DCPs. We aimed to identify exposure profiles for the long‐term weekly use of DCPs by latent class analysis (LCA) and assess their associations with asthma.MethodsLCA was conducted on data from 1143 young adults initially recruited in the German centers of Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC) and followed up three times. In our LCA model, we included the use of cleaning sprays, disinfectant sprays, and nonspray disinfection methods, measured at ages 19–24 (first assessment) and 29–34 years (second assessment). Associations between identified exposure profiles and current as well as incident asthma/wheeze were evaluated by logistic regression.ResultsWe identified five long‐term exposure profiles to DCPs (latent classes): no weekly use of DCPs (55% of participants), use in first assessment (7%), use in second assessment (18%), persistent use (8%), and persistent cleaning sprays use (12%). Compared to “no weekly use,” being in the “persistent use” profile was associated with both current asthma (OR = 1.68, 95% CI = [0.48–5.88]) and current wheeze (OR = 1.71, 95% CI = [0.75–3.90]). For incident asthma/wheeze, interval estimates were very wide.ConclusionsOur study identified five distinct long‐term exposure profiles to DCPs. Among those, only a persistent weekly use of multiple DCPs over time seemed to have an adverse effect on asthma. However, large confidence intervals indicate considerable uncertainty.
{"title":"Exposure Profiles for the Long‐Term Use of Disinfectants and Cleaning Products and Asthma","authors":"Emilie Pacheco Da Silva, Tobias Weinmann, Jessica Gerlich, Gudrun Weinmayr, Jon Genuneit, Dennis Nowak, Erika von Mutius, Christian Vogelberg, Katja Radon, Felix Forster","doi":"10.1111/all.16456","DOIUrl":"https://doi.org/10.1111/all.16456","url":null,"abstract":"BackgroundUsing disinfectants and cleaning products (DCPs) at home and work is known to influence both the onset and course of asthma, but most epidemiological studies did not consider the multiplicity and correlations of exposures to DCPs. We aimed to identify exposure profiles for the long‐term weekly use of DCPs by latent class analysis (LCA) and assess their associations with asthma.MethodsLCA was conducted on data from 1143 young adults initially recruited in the German centers of Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC) and followed up three times. In our LCA model, we included the use of cleaning sprays, disinfectant sprays, and nonspray disinfection methods, measured at ages 19–24 (first assessment) and 29–34 years (second assessment). Associations between identified exposure profiles and current as well as incident asthma/wheeze were evaluated by logistic regression.ResultsWe identified five long‐term exposure profiles to DCPs (latent classes): no weekly use of DCPs (55% of participants), use in first assessment (7%), use in second assessment (18%), persistent use (8%), and persistent cleaning sprays use (12%). Compared to “no weekly use,” being in the “persistent use” profile was associated with both current asthma (OR = 1.68, 95% CI = [0.48–5.88]) and current wheeze (OR = 1.71, 95% CI = [0.75–3.90]). For incident asthma/wheeze, interval estimates were very wide.ConclusionsOur study identified five distinct long‐term exposure profiles to DCPs. Among those, only a persistent weekly use of multiple DCPs over time seemed to have an adverse effect on asthma. However, large confidence intervals indicate considerable uncertainty.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"5 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886909","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}
A. Lemoine, N. Kapel, I. Nicolis, P. Tounian, A. Bruneau, N. Kapandji, K. Adel‐Patient, M. Thomas
BackgroundFood protein‐induced enterocolitis syndrome (FPIES) is a non‐IgE‐mediated allergy without known biomarkers. We aimed to compare fecal biomarkers related to gut inflammation and immunity in children with FPIES, with resolved FPIES (tolerant), and in matched controls.MethodsStools were collected from FPIES children on elimination diet, before and after an oral food challenge (OFC) performed to assess their natural tolerance, at the end of a follow‐up in tolerant FPIES children, and in matched controls (1:1 ratio). Concentrations of calprotectin, EDN (eosinophilic derived neurotoxin), and secretory IgA (sIgA) underwent comparative paired analysis.ResultsThirty‐eight patients were included (age: 1.3 years old, interquartile range: IQR [0.9–2.0]), of which 22 became tolerant during follow‐up. Upon inclusion, allergic patients and controls had similar concentrations of calprotectin (38 μg/g [8–85] vs. 27 μg/g [11–46], p = 0.15) and EDN (504 ng/g [275–1252] vs. 516 ng/g [215–844], p = 0.86). However, concentrations of these inflammatory biomarkers increased transiently after a failed OFC (p < 0.001 and p = 0.01 respectively), without correlating with the severity of an allergic reaction. sIgA were higher in allergic than in tolerant patients: 2224 μg/g [878–3529] vs. 794 μg/g [699–1767] (p < 0.01). Calprotectin, EDN, and sIgA were comparable in tolerant patients and controls. sIgA less than 2637 μg/g had a negative predictive value of 75.3% for the differentiation allergic patients from tolerant patients and controls (area under curve: 0.63, 95% CI: 0.52–0.74).ConclusionA few days after an acute allergic reaction, there was no detectable chronic gut inflammation in FPIES. sIgA may be a useful tool for clinicians in timing OFC.
{"title":"Identification of Gut Biomarkers of FPIES in a Longitudinal Comparative Pediatric Study","authors":"A. Lemoine, N. Kapel, I. Nicolis, P. Tounian, A. Bruneau, N. Kapandji, K. Adel‐Patient, M. Thomas","doi":"10.1111/all.16457","DOIUrl":"https://doi.org/10.1111/all.16457","url":null,"abstract":"BackgroundFood protein‐induced enterocolitis syndrome (FPIES) is a non‐IgE‐mediated allergy without known biomarkers. We aimed to compare fecal biomarkers related to gut inflammation and immunity in children with FPIES, with resolved FPIES (tolerant), and in matched controls.MethodsStools were collected from FPIES children on elimination diet, before and after an oral food challenge (OFC) performed to assess their natural tolerance, at the end of a follow‐up in tolerant FPIES children, and in matched controls (1:1 ratio). Concentrations of calprotectin, EDN (eosinophilic derived neurotoxin), and secretory IgA (sIgA) underwent comparative paired analysis.ResultsThirty‐eight patients were included (age: 1.3 years old, interquartile range: IQR [0.9–2.0]), of which 22 became tolerant during follow‐up. Upon inclusion, allergic patients and controls had similar concentrations of calprotectin (38 μg/g [8–85] vs. 27 μg/g [11–46], <jats:italic>p</jats:italic> = 0.15) and EDN (504 ng/g [275–1252] vs. 516 ng/g [215–844], <jats:italic>p</jats:italic> = 0.86). However, concentrations of these inflammatory biomarkers increased transiently after a failed OFC (<jats:italic>p</jats:italic> < 0.001 and <jats:italic>p</jats:italic> = 0.01 respectively), without correlating with the severity of an allergic reaction. sIgA were higher in allergic than in tolerant patients: 2224 μg/g [878–3529] vs. 794 μg/g [699–1767] (<jats:italic>p</jats:italic> < 0.01). Calprotectin, EDN, and sIgA were comparable in tolerant patients and controls. sIgA less than 2637 μg/g had a negative predictive value of 75.3% for the differentiation allergic patients from tolerant patients and controls (area under curve: 0.63, 95% CI: 0.52–0.74).ConclusionA few days after an acute allergic reaction, there was no detectable chronic gut inflammation in FPIES. sIgA may be a useful tool for clinicians in timing OFC.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"31 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886690","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}
Jie Ma, Debra J. Palmer, Donna Geddes, Ching Tat Lai, Alethea Rea, Susan L. Prescott, Nina D'Vaz, Lisa F. Stinson
Early infancy is a critical period for immune development. In addition to being the primary food source during early infancy, human milk also provides multiple bioactive components that shape the infant gut microbiome and immune system and provides a constant source of exposure to maternal microbiota. Given the potential interplay between allergic diseases and the human microbiome, this study aimed to characterise the milk microbiome of allergic mothers. Full‐length 16S rRNA gene sequencing was performed on milk samples collected at 3 and 6 months postpartum from 196 women with allergic disease. Multivariate linear mixed models were constructed to identify the maternal, infant, and environmental determinants of the milk microbiome. Human milk microbiome composition and beta diversity varied over time (PERMANOVA R2 = 0.011, p = 0.011). The season of infant birth emerged as the strongest determinant of the microbiome community structure (PERMANOVA R2 = 0.014, p = 0.011) with impacts on five of the most abundant taxa. The milk microbiome also varied according to the type of maternal allergic disease (allergic rhinitis, asthma, atopic dermatitis, and food allergy). Additionally, infant formula exposure reduced the relative abundance of several typical oral taxa in milk. In conclusion, the milk microbiome of allergic mothers was strongly shaped by the season of infant birth, maternal allergic disease phenotype, and infant feeding mode. Maternal allergic disease history and infant season of birth should therefore be considered in future studies of infant and maternal microbiota.Trial Registration: ClinicalTrials.gov identifier: ACTRN12606000281594
{"title":"Maternal Allergic Disease Phenotype and Infant Birth Season Influence the Human Milk Microbiome","authors":"Jie Ma, Debra J. Palmer, Donna Geddes, Ching Tat Lai, Alethea Rea, Susan L. Prescott, Nina D'Vaz, Lisa F. Stinson","doi":"10.1111/all.16442","DOIUrl":"https://doi.org/10.1111/all.16442","url":null,"abstract":"Early infancy is a critical period for immune development. In addition to being the primary food source during early infancy, human milk also provides multiple bioactive components that shape the infant gut microbiome and immune system and provides a constant source of exposure to maternal microbiota. Given the potential interplay between allergic diseases and the human microbiome, this study aimed to characterise the milk microbiome of allergic mothers. Full‐length 16S rRNA gene sequencing was performed on milk samples collected at 3 and 6 months postpartum from 196 women with allergic disease. Multivariate linear mixed models were constructed to identify the maternal, infant, and environmental determinants of the milk microbiome. Human milk microbiome composition and beta diversity varied over time (PERMANOVA <jats:italic>R</jats:italic><jats:sup>2</jats:sup> = 0.011, <jats:italic>p</jats:italic> = 0.011). The season of infant birth emerged as the strongest determinant of the microbiome community structure (PERMANOVA <jats:italic>R</jats:italic><jats:sup>2</jats:sup> = 0.014, <jats:italic>p</jats:italic> = 0.011) with impacts on five of the most abundant taxa. The milk microbiome also varied according to the type of maternal allergic disease (allergic rhinitis, asthma, atopic dermatitis, and food allergy). Additionally, infant formula exposure reduced the relative abundance of several typical oral taxa in milk. In conclusion, the milk microbiome of allergic mothers was strongly shaped by the season of infant birth, maternal allergic disease phenotype, and infant feeding mode. Maternal allergic disease history and infant season of birth should therefore be considered in future studies of infant and maternal microbiota.Trial Registration: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"http://clinicaltrials.gov\">ClinicalTrials.gov</jats:ext-link> identifier: ACTRN12606000281594","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886908","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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