Background: Asthma exacerbations during pregnancy are associated with adverse maternal and perinatal outcomes. Identifying modifiable risk factors is essential for improving health outcomes. We aimed to describe exacerbation patterns during pregnancy and identify exacerbation risk factors, particularly modifiable risk factors such as inhaled corticosteroid use.
Methods: This was a cohort study using UK primary care and hospital data (2004-2020) to identify pregnant women with asthma. Exacerbations were defined as a short course of oral corticosteroids, emergency department visit or unscheduled hospital admission. Multivariable logistic regression was used to assess associations between maternal characteristics and exacerbations (primary outcome) and inhaled corticosteroid use (secondary outcome).
Results: Among 40 196 pregnant women with asthma, total exacerbations declined by ∼30% during pregnancy. However, exacerbations associated with hospital admission increased by 30-45% during the second and third trimesters, declining abruptly after delivery. Inhaled corticosteroid prescriptions were reduced in 31% of women during pregnancy. Decreased inhaled corticosteroid use was associated with suboptimal asthma control pre-pregnancy, age, ethnicity and smoking. The strongest exacerbation risk factors were a history of exacerbations (adjusted OR 4.09, 95% CI 3.81-4.39), reduced inhaled corticosteroid use during pregnancy (adjusted OR 2.29, 95% CI 2.12-2.47) and ≥4 prescriptions per year for inhaled corticosteroids plus another preventer before pregnancy (adjusted odds ratio 2.11, 95% CI 1.87-2.37). Additional risk factors included blood eosinophilia, smoking and obesity.
Conclusions: Despite fewer total exacerbations, exacerbations associated with a hospital admission increased during pregnancy. One third of women reduced inhaled corticosteroid use during pregnancy, yet this was the second largest exacerbation risk factor and is completely modifiable. Other major risk factors were type 2 inflammation and another modifiable risk factor, suboptimal asthma control pre-pregnancy.
{"title":"Pregnancy, asthma and exacerbations: a population-based cohort.","authors":"Bohee Lee, Ernie Wong, Tricia Tan, Hitasha Rupani, Chloe I Bloom","doi":"10.1183/13993003.01327-2025","DOIUrl":"10.1183/13993003.01327-2025","url":null,"abstract":"<p><strong>Background: </strong>Asthma exacerbations during pregnancy are associated with adverse maternal and perinatal outcomes. Identifying modifiable risk factors is essential for improving health outcomes. We aimed to describe exacerbation patterns during pregnancy and identify exacerbation risk factors, particularly modifiable risk factors such as inhaled corticosteroid use.</p><p><strong>Methods: </strong>This was a cohort study using UK primary care and hospital data (2004-2020) to identify pregnant women with asthma. Exacerbations were defined as a short course of oral corticosteroids, emergency department visit or unscheduled hospital admission. Multivariable logistic regression was used to assess associations between maternal characteristics and exacerbations (primary outcome) and inhaled corticosteroid use (secondary outcome).</p><p><strong>Results: </strong>Among 40 196 pregnant women with asthma, total exacerbations declined by ∼30% during pregnancy. However, exacerbations associated with hospital admission increased by 30-45% during the second and third trimesters, declining abruptly after delivery. Inhaled corticosteroid prescriptions were reduced in 31% of women during pregnancy. Decreased inhaled corticosteroid use was associated with suboptimal asthma control pre-pregnancy, age, ethnicity and smoking. The strongest exacerbation risk factors were a history of exacerbations (adjusted OR 4.09, 95% CI 3.81-4.39), reduced inhaled corticosteroid use during pregnancy (adjusted OR 2.29, 95% CI 2.12-2.47) and ≥4 prescriptions per year for inhaled corticosteroids plus another preventer before pregnancy (adjusted odds ratio 2.11, 95% CI 1.87-2.37). Additional risk factors included blood eosinophilia, smoking and obesity.</p><p><strong>Conclusions: </strong>Despite fewer total exacerbations, exacerbations associated with a hospital admission increased during pregnancy. One third of women reduced inhaled corticosteroid use during pregnancy, yet this was the second largest exacerbation risk factor and is completely modifiable. Other major risk factors were type 2 inflammation and another modifiable risk factor, suboptimal asthma control pre-pregnancy.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12713386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1183/13993003.01046-2025
Agathe Béranger,Belén P Solans,Ryo Miyakawa,Helen McIlleron,Joel Tarning,Ira Shah,Blessed Winston Aruldhas,Binu Susan Mathew,Awewura Kwara,Charles A Peloquin,Aparna Mukherjee,Rakesh Lodha,Paolo Denti,Edmund V Capparelli,Jennifer J Kiser,Adrie Bekker,Chishala Chabala,Louise Choo,Anna Turkova,Fajri Gafar,Rovina Ruslami,Heda M Nataprawira,Scott K Heysell,Tania A Thomas,Thirumurthy Velpandian,Jeremy N Day,Nguyen Duc Bang,Kelly Dooley,Radojka M Savic
BACKGROUNDIsoniazid is a cornerstone of management therapy for tuberculosis. The aim was to determine the association between isoniazid exposure and clinical outcomes, to develop a pharmacokinetic model, and to optimize the dosing regimen in children treated for drug-susceptible tuberculosis.METHODSFor this individual participant data meta-analysis, PubMed was searched for observational studies, involving children (0-18 years), being treated for drug susceptible tuberculosis. The relationship between isoniazid exposure and clinical outcomes was analyzed using a mixed-effects logistic regression model. Pharmacokinetic parameters were described using nonlinear mixed effects modeling. Pharmacokinetic target was the median adult area under the concentration time curve (AUCss) of 23.4 mg.h·L-1.RESULTSSix studies provided clinical outcomes, including 405 patients, of which 21% had unfavorable outcomes. Sixteen studies (1255 patients) were included in the pharmacokinetic model. Unfavorable outcomes were only related to lower BMI for age Z-score (OR 0.96, 95% CI 0.93-0.99, p<0.05). Isoniazid exposure was impacted by NAT2 genotype, weight, age, and nutritional status (using BMI for age Z-score). With currently recommended WHO doses, isoniazid exposure was similar to that of adults. Pharmacokinetic target attainment was 71.7% and 29.5% for slow and fast metabolizers, respectively (p<0.05); 50.5% for patients with a BAZ>0 and 42.6% for malnourished patients (BAZ<-2) (p<0.05). Model-informed dosing regimen showed that fast metabolizers could benefit from higher isoniazid dosing, especially in malnourished children.CONCLUSIONOur findings showed that the only predictor of unfavorable clinical outcomes was a lower BMI for age Z-score. We support the current WHO-recommended dosing regimen for isoniazid. To equalize and attain our pharmacological target for all children, dosing regimens could be adjusted on NAT2 genotype and nutritional status.
背景：双烟肼是结核病管理治疗的基石。目的是确定异烟肼暴露与临床结果之间的关系，建立药代动力学模型，并优化治疗药物敏感结核病儿童的给药方案。方法：对于这项个体参与者数据荟萃分析，检索PubMed中涉及儿童（0-18岁）的观察性研究，这些儿童正在接受药物敏感结核病的治疗。使用混合效应logistic回归模型分析异烟肼暴露与临床结果的关系。采用非线性混合效应模型描述药代动力学参数。药代动力学目标为23.4 mg.h·L-1浓度时间曲线下的中位成人面积。结果6项研究提供了临床结果，包括405例患者，其中21%的患者预后不良。16项研究（1255例患者）纳入药代动力学模型。不良结局仅与年龄z评分较低的BMI相关(OR 0.96, 95% CI 0.93-0.99，营养不良患者的p0和42.6% (BAZ<-2) （p<0.05）。基于模型的给药方案显示，快速代谢者可能受益于较高的异烟肼剂量，特别是在营养不良儿童中。结论：我们的研究结果表明，不良临床结果的唯一预测因子是年龄z分数较低的BMI。我们支持目前世卫组织推荐的异烟肼给药方案。为了平衡和达到我们对所有儿童的药理学目标，可以根据NAT2基因型和营养状况调整给药方案。
{"title":"Efficacy of isoniazid in pediatric tuberculosis: an individual participant data meta-analysis.","authors":"Agathe Béranger,Belén P Solans,Ryo Miyakawa,Helen McIlleron,Joel Tarning,Ira Shah,Blessed Winston Aruldhas,Binu Susan Mathew,Awewura Kwara,Charles A Peloquin,Aparna Mukherjee,Rakesh Lodha,Paolo Denti,Edmund V Capparelli,Jennifer J Kiser,Adrie Bekker,Chishala Chabala,Louise Choo,Anna Turkova,Fajri Gafar,Rovina Ruslami,Heda M Nataprawira,Scott K Heysell,Tania A Thomas,Thirumurthy Velpandian,Jeremy N Day,Nguyen Duc Bang,Kelly Dooley,Radojka M Savic","doi":"10.1183/13993003.01046-2025","DOIUrl":"https://doi.org/10.1183/13993003.01046-2025","url":null,"abstract":"BACKGROUNDIsoniazid is a cornerstone of management therapy for tuberculosis. The aim was to determine the association between isoniazid exposure and clinical outcomes, to develop a pharmacokinetic model, and to optimize the dosing regimen in children treated for drug-susceptible tuberculosis.METHODSFor this individual participant data meta-analysis, PubMed was searched for observational studies, involving children (0-18 years), being treated for drug susceptible tuberculosis. The relationship between isoniazid exposure and clinical outcomes was analyzed using a mixed-effects logistic regression model. Pharmacokinetic parameters were described using nonlinear mixed effects modeling. Pharmacokinetic target was the median adult area under the concentration time curve (AUCss) of 23.4 mg.h·L-1.RESULTSSix studies provided clinical outcomes, including 405 patients, of which 21% had unfavorable outcomes. Sixteen studies (1255 patients) were included in the pharmacokinetic model. Unfavorable outcomes were only related to lower BMI for age Z-score (OR 0.96, 95% CI 0.93-0.99, p<0.05). Isoniazid exposure was impacted by NAT2 genotype, weight, age, and nutritional status (using BMI for age Z-score). With currently recommended WHO doses, isoniazid exposure was similar to that of adults. Pharmacokinetic target attainment was 71.7% and 29.5% for slow and fast metabolizers, respectively (p<0.05); 50.5% for patients with a BAZ>0 and 42.6% for malnourished patients (BAZ<-2) (p<0.05). Model-informed dosing regimen showed that fast metabolizers could benefit from higher isoniazid dosing, especially in malnourished children.CONCLUSIONOur findings showed that the only predictor of unfavorable clinical outcomes was a lower BMI for age Z-score. We support the current WHO-recommended dosing regimen for isoniazid. To equalize and attain our pharmacological target for all children, dosing regimens could be adjusted on NAT2 genotype and nutritional status.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"29 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777459","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 : 2025-12-18Print Date: 2025-12-01DOI: 10.1183/13993003.01610-2025
Mitja Jevnikar, Philippe Brenot, Mithum Kularatne, Alexandre Rodière, Elise Noël-Savina, Ari Chaouat, Samuel Dolidon, Athénaïs Boucly, Olivier Sitbon, Laurent Savale, David Montani, Olaf Mercier, Marc Humbert, Elie Fadel, Xavier Jaïs
{"title":"Chronic thromboembolic pulmonary hypertension associated with venous thoracic outlet syndrome: a retrospective case series.","authors":"Mitja Jevnikar, Philippe Brenot, Mithum Kularatne, Alexandre Rodière, Elise Noël-Savina, Ari Chaouat, Samuel Dolidon, Athénaïs Boucly, Olivier Sitbon, Laurent Savale, David Montani, Olaf Mercier, Marc Humbert, Elie Fadel, Xavier Jaïs","doi":"10.1183/13993003.01610-2025","DOIUrl":"10.1183/13993003.01610-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458171","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 : 2025-12-18Print Date: 2025-12-01DOI: 10.1183/13993003.00728-2025
Jessica Pohl, Matthias I Gröschel, Nino Neumann, Anett Tillmann, Stephan Waldeck, Tobias Schneider, Daniel Overhoff, Stephanie G Lange, Thomas Bucksch, Rebecca Peuker, Dominic Rauschning, Gwendolyn Scheumann, Lorenz Scheit, Maximilian Schreiner, Werner Wenzel, Kai Kehe, Inna Friesen, Viola Dreyer, Stefan Niemann, Leif-Erik Sander, Martin Witzenrath, Geraldine Nouailles, Christian M Zobel
{"title":"Active case finding for tuberculosis among Ukrainian soldiers by German armed forces.","authors":"Jessica Pohl, Matthias I Gröschel, Nino Neumann, Anett Tillmann, Stephan Waldeck, Tobias Schneider, Daniel Overhoff, Stephanie G Lange, Thomas Bucksch, Rebecca Peuker, Dominic Rauschning, Gwendolyn Scheumann, Lorenz Scheit, Maximilian Schreiner, Werner Wenzel, Kai Kehe, Inna Friesen, Viola Dreyer, Stefan Niemann, Leif-Erik Sander, Martin Witzenrath, Geraldine Nouailles, Christian M Zobel","doi":"10.1183/13993003.00728-2025","DOIUrl":"10.1183/13993003.00728-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12713385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18Print Date: 2025-12-01DOI: 10.1183/13993003.E6606-2025
{"title":"<i>ERJ</i> Podcast December 2025: Year in review.","authors":"","doi":"10.1183/13993003.E6606-2025","DOIUrl":"https://doi.org/10.1183/13993003.E6606-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"66 6","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780680","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 : 2025-12-18DOI: 10.1183/13993003.52563-2024
{"title":"\"Natural disasters and respiratory health.\" I. Annesi-Maesano, H. Bayram, L. Cecchi, et al. Eur Respir J 2025; 66: 2402563.","authors":"","doi":"10.1183/13993003.52563-2024","DOIUrl":"https://doi.org/10.1183/13993003.52563-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"125 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777465","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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