Alyson W Wong,Daniel-Costin Marinescu,Kerri A Johannson,Veronica Marcoux,Jolene H Fisher,Deborah Assayag,Helene Manganas,Martin Kolb,Christopher J Ryerson,Sabina A Guler,
{"title":"The impact of frailty on prescribing patterns and medication tolerability in interstitial lung disease.","authors":"Alyson W Wong,Daniel-Costin Marinescu,Kerri A Johannson,Veronica Marcoux,Jolene H Fisher,Deborah Assayag,Helene Manganas,Martin Kolb,Christopher J Ryerson,Sabina A Guler, ","doi":"10.1183/13993003.01533-2025","DOIUrl":"https://doi.org/10.1183/13993003.01533-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"160 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351768","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":"Reply: Colonisation versus infection in ICU-acquired pneumonia.","authors":"Justin de Brabander,Tom van der Poll","doi":"10.1183/13993003.01700-2025","DOIUrl":"https://doi.org/10.1183/13993003.01700-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"1 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305630","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}
Zhaozhong Zhu,Conglin Liu,Carole Ober,Carlos A Camargo
{"title":"Gene-environment interaction at 17q12-q21 locus and its role in asthma pathogenesis.","authors":"Zhaozhong Zhu,Conglin Liu,Carole Ober,Carlos A Camargo","doi":"10.1183/13993003.01232-2025","DOIUrl":"https://doi.org/10.1183/13993003.01232-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"130 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305335","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":"Functional sequence variants of intergenic long noncoding RNA on chromosome 17q21 are associated with asthma.","authors":"Kwei-Yan Liu, Jia-Jyun Sie, Yajing Gao, Yen-Li Lo, Chao-Chien Wu, Chin-Chou Wang, Chau-Chyun Sheu, Ruay-Sheng Lai, Sum-Yee Leung, Chi-Cheng Lin, Yu-Feng Wei, Ching-Hsiung Lin, Sheng-Hao Lin, Jeng-Yuan Hsu, Wei-Chang Huang, Chia-Cheng Tseng, Yung-Fa Lai, Meng-Hsuan Cheng, Huang-Chi Chen, Chih-Jen Yang, Yuan-Ting Hsu, Chian-Heng Su, Shih-Chang Hsu, Wen-Yu Chung, Ming-Tsuen Hsieh, Li-Chen Chen, Chih-Hsing Hung, Chon-Lin Lee, Ming-Shyan Huang, Yufeng Zhou, Cathy S J Fann, Shau-Ku Huang","doi":"10.1183/13993003.00847-2025","DOIUrl":"10.1183/13993003.00847-2025","url":null,"abstract":"<p><strong>Background: </strong>The genetic and molecular basis of asthma remains unclear and its gene-environment interaction is still enigmatic. In the present study, we aimed to identify asthma-causing genetic variants and their interactions with the environment.</p><p><strong>Methods: </strong>We performed case-control genome-wide association studies on individuals of Han Chinese descent from the Taiwan Biobank (n=4877 cases, n=98 218 controls) to identify asthma susceptibility loci, validated in a hospital-based population of subjects (n=2595). The 10-15-year exposures to cumulative ambient particulate matter with a diameter of <2.5 μm (PM<sub>2.5</sub>) and polycyclic aromatic hydrocarbons (PAHs) were assessed for gene-environment relationships. The function of the newly identified long noncoding RNA <i>lncZPBP2-3</i> and its interactions with PM<sub>2.5</sub> and PAH exposure were analysed using RNA immunoprecipitation, RNA pulldown, reverse transcription quantitative PCR and Western blotting.</p><p><strong>Results: </strong>Chromosome 17q12-21 was found to be a significant risk region, encompassing variants of <i>lncZPBP2-3</i> and its neighbouring genes, which interacted with increasing exposure to PM<sub>2.5</sub> and adsorbed PAHs. The expression of <i>lncZPBP2-3</i> was elevated, correlating with the expression of its neighbouring genes, in the peripheral blood of patients with asthma compared to that in controls. Unlike non-risk <i>lncZPBP2-3</i>, the risk variant of <i>lncZPBP2-3</i> disrupted transcriptional suppression of the risk locus <i>via</i> its interaction with the transcription insulator CCCTC-binding factor, concomitant with the higher expression levels of neighbouring genes in individuals with the risk genotype.</p><p><strong>Conclusion: </strong>A functional variant of lncRNA, <i>lncZPBP2-3</i>, was significantly associated with asthma and is inducible by environmental PAH, suggesting a potentially novel genetic and molecular mechanism of asthma.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559593","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}
Isabella Annesi-Maesano, Hasan Bayram, Lorenzo Cecchi, Daniel Croft, Gennaro D'Amato, Arundhati Garud, Ozgecan Kayalar, Mehdi Misraedi, Subhabrata Moitra, Vanitha Sampath, Neeta Thakur, Kari Nadeau, John Balmes
{"title":"Natural disasters and respiratory health.","authors":"Isabella Annesi-Maesano, Hasan Bayram, Lorenzo Cecchi, Daniel Croft, Gennaro D'Amato, Arundhati Garud, Ozgecan Kayalar, Mehdi Misraedi, Subhabrata Moitra, Vanitha Sampath, Neeta Thakur, Kari Nadeau, John Balmes","doi":"10.1183/13993003.02563-2024","DOIUrl":"10.1183/13993003.02563-2024","url":null,"abstract":"<p><p>Natural disasters (including heatwaves, wildfires, hurricanes, floods, earthquakes and volcanic eruptions) significantly impact respiratory health, posing heightened risks to vulnerable populations such as individuals with pre-existing conditions, children, and the elderly. This review explores the complex relationship between natural catastrophes and respiratory health, emphasising the roles of chemical pollutants, biocontaminants and meteorological factors. Epidemiological evidence highlights alarming trends, including increased asthma exacerbations, COPD hospitalisations and respiratory infections following these events. During heatwaves, elevated ozone levels and emissions from power generation for air conditioning exacerbate respiratory conditions, while fine and ultrafine particulate matter, particularly during dust storms and wildfires, emerge as a major contributor to respiratory morbidity and mortality. Volcanic eruptions release hazardous gases, corrosive minerals and plumes of particles and dust into the atmosphere, which exacerbate symptoms in individuals with pre-existing respiratory conditions. Thunderstorms often increase airborne pollen and mould concentrations, triggering episodes of thunderstorm asthma. Earthquake-damaged buildings are significant sources of dust, worsening respiratory symptoms among affected populations. Floods are the origin of mould proliferation, responsible for asthma and other respiratory diseases. First responders, such as firefighters, face acute and potentially chronic respiratory issues due to prolonged exposure to chemical pollutants and biocontaminants during rescue operations. Marginalised communities disproportionately bear the brunt of these health impacts due to systemic vulnerabilities and limited adaptive capacities. This review underscores the escalating respiratory health threats posed by natural disasters amid ongoing climate change. An integrated approach is needed to address these challenges through improved understanding, targeted interventions, and proactive measures to mitigate risks.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948199","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}
Katherine Jankowski, Sarah E Lemay, Daniel Lozano-Ojalvo, Leticia Pérez-Rodríguez, Mélanie Sauvaget, Sandra Breuils-Bonnet, Karina Formoso, Vineeta Jagana, Maria T Ochoa, Shihong Zhang, Javier Milara, Julio Cortijo, Irene C Turnbull, Steeve Provencher, Sebastien Bonnet, Jordi Ochando, Frank Lezoualc'h, Malik Bisserier, Lahouaria Hadri
{"title":"Pharmacological inhibition of Epac1 protects against pulmonary fibrosis by blocking FoxO3a neddylation.","authors":"Katherine Jankowski, Sarah E Lemay, Daniel Lozano-Ojalvo, Leticia Pérez-Rodríguez, Mélanie Sauvaget, Sandra Breuils-Bonnet, Karina Formoso, Vineeta Jagana, Maria T Ochoa, Shihong Zhang, Javier Milara, Julio Cortijo, Irene C Turnbull, Steeve Provencher, Sebastien Bonnet, Jordi Ochando, Frank Lezoualc'h, Malik Bisserier, Lahouaria Hadri","doi":"10.1183/13993003.02250-2024","DOIUrl":"10.1183/13993003.02250-2024","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is marked by progressive lung scarring with no existing cure, emphasising the need for new therapeutic targets. Current evidence suggests that cyclic adenosine monophosphate (cAMP) mitigates lung fibroblast proliferation <i>via</i> the protein kinase A pathway, but the impact of exchange proteins directly activated by cAMP 1 (Epac1) on IPF remains unexplored.</p><p><strong>Objective: </strong>To investigate the role of Epac1 in IPF progression.</p><p><strong>Methods: </strong>We examined lung samples from IPF patients and controls, and from a bleomycin-induced mouse model of pulmonary fibrosis. The effects of Epac were analysed in knockout mice and through modulation using viral vectors. The Epac1-specific small compound inhibitor AM-001 was evaluated <i>in vitro</i> using lung fibroblasts from patients with IPF, <i>in vivo</i> in bleomycin mice and <i>ex vivo</i> in IPF precision-cut lung slices.</p><p><strong>Results: </strong>Increased Epac1 expression was observed in lung tissues from IPF patients, fibrotic fibroblasts and bleomycin-challenged mice. Genetic or pharmacological inhibition of Epac1 with AM-001 decreased proliferation in normal and IPF fibroblasts, and reduced expression of profibrotic markers such as α-smooth muscle actin, transforming growth factor-β/SMAD family member 2/3, and interleukin-6/signal transducer and activator of transcription 3 pathways. Epac1-specific inhibition consistently protected against bleomycin-induced lung injury and fibrosis, suggesting significant therapeutic potential. Global gene expression profiling indicated a reduced profibrotic gene signature and neddylation pathway components in Epac1-deficient fibroblasts and human-derived lung cells. Mechanistically, the protective effects may involve inhibiting the neddylation pathway and preventing neural precursor cell expressed, developmentally downregulated 8 (NEDD8) activation, which in turn reduces the degradation of forkhead box protein O3 by NEDD8. Additionally, these effects may be enhanced while also limiting the proliferation of lung-infiltrating monocytes.</p><p><strong>Conclusions: </strong>Our findings demonstrate that Epac1 regulates fibroblast activity in pulmonary fibrosis, and that targeting Epac1 with the pharmacological specific inhibitor AM-001 offers a promising therapeutic approach for treating IPF disease.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607891","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}
Meliane de Oliveira Daud,Roberta Pulcheri Ramos,Gabriela Oliveira Siqueira Costa,Andrei A A de Campos Cordeiro,Camila Melo Coelho Loureiro,Rudolf K F Oliveira,Luiz Eduardo Nery,Eloara V M Ferreira,Jaquelina Sonoe Ota-Arakaki
{"title":"Oxygen pulse plateau as a qualitative marker for risk stratification in PAH.","authors":"Meliane de Oliveira Daud,Roberta Pulcheri Ramos,Gabriela Oliveira Siqueira Costa,Andrei A A de Campos Cordeiro,Camila Melo Coelho Loureiro,Rudolf K F Oliveira,Luiz Eduardo Nery,Eloara V M Ferreira,Jaquelina Sonoe Ota-Arakaki","doi":"10.1183/13993003.01206-2025","DOIUrl":"https://doi.org/10.1183/13993003.01206-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"53 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305336","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}