European Respiratory Journal最新文献

{"title":"Genome-wide association study of susceptibility to <i>Pseudomonas aeruginosa</i> infection in cystic fibrosis.","authors":"Boxi Lin, Jiafen Gong, Katherine Keenan, Fan Lin, Yu-Chung Lin, Julie Mésinèle, Claire Calmel, Badreddine Mohand Oumoussa, Pierre-Yves Boëlle, Loïc Guillot, Harriet Corvol, Valerie Waters, Lei Sun, Lisa J Strug","doi":"10.1183/13993003.00062-2024","DOIUrl":"10.1183/13993003.00062-2024","url":null,"abstract":"<p><strong>Background: </strong><i>Pseudomonas aeruginosa</i> is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing <i>CFTR</i> (CF transmembrane conductance regulator) variations contribute ∼85% of the variation in chronic <i>P. aeruginosa</i> infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to <i>P. aeruginosa</i> infection.</p><p><strong>Materials and methods: </strong>We conducted a genome-wide association study of chronic <i>P. aeruginosa</i> infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic <i>P. aeruginosa</i> infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bidirectional Mendelian randomisation analysis.</p><p><strong>Results: </strong>Two novel genome-wide significant loci with lead single nucleotide polymorphisms (SNPs) rs62369766 (chr5p12; p=1.98×10^-8) and rs927553 (chr13q12.12; p=1.91×10^-8) were associated with chronic <i>P. aeruginosa</i> infection age. The rs62369766 locus was validated using an independent French cohort (n=501). Furthermore, the PRS constructed from CF lung function-associated SNPs was significantly associated with chronic <i>P. aeruginosa</i> infection age (p=0.002). Finally, our analysis presented evidence for a causal effect of lung function on chronic <i>P. aeruginosa</i> infection age (β=0.782 years, p=4.24×10^-4). In the reverse direction, we observed a moderate effect (β=0.002, p=0.012).</p><p><strong>Conclusions: </strong>We identified two novel loci that are associated with chronic <i>P. aeruginosa</i> infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between <i>P. aeruginosa</i> infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections, which account for significant remaining morbidity in CF.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906376","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}

{"title":"Pulmonary gas exchange in relation to exercise pulmonary hypertension in patients with heart failure with preserved ejection fraction.","authors":"Bryce N Balmain, Andrew R Tomlinson, Josh T Goh, James P MacNamara, Denis J Wakeham, Tiffany L Brazile, Michael G Leahy, Kevin C Lutz, Linda S Hynan, Benjamin D Levine, Satyam Sarma, Tony G Babb","doi":"10.1183/13993003.00722-2024","DOIUrl":"https://doi.org/10.1183/13993003.00722-2024","url":null,"abstract":"<p><strong>Background: </strong>Exercise pulmonary hypertension (ePH), defined as a mean pulmonary artery pressure (mPAP)/cardiac output (Qc) slope >3 WU during exercise, is common in patients with heart failure with preserved ejection fraction (HFpEF). However, the pulmonary gas exchange-related effects of an exaggerated ePH (EePH) response are not well-defined, especially in relation to dyspnea on exertion (DOE) and exercise intolerance.</p><p><strong>Methods: </strong>48 HFpEF patients underwent invasive (pulmonary and radial artery catheters) constant-load (20W) and maximal incremental cycle testing. Hemodynamic measurements (mPAP and Qc), arterial blood and expired gases, and ratings of breathlessness (RPB, Borg 0-10) were obtained. The mPAP/Qc slope was calculated from rest-to-20W. Those with a mPAP/Qc slope >4.2 (median) were classified as HFpEF+EePH (n=24) and those with a mPAP/Qc slope <4.2 were classified as HFpEF (without EePH) (n=24). The A-aDO₂, V_D/V_T (Bohr equation), and the V_E/VCO₂ slope (from rest-to-20W) were calculated.</p><p><strong>Results: </strong>PaO₂ was lower (p=0.03), and V_D/V_T was higher (p=0.03) at peak exercise in HFpEF+EePH compared with HFpEF. A-aDO₂ was similar at peak exercise between groups (p=0.14); however, HFpEF+EePH achieved the peak A-aDO₂ at a lower peak work rate (p<0.01). The V_E/VCO₂ slope was higher in HFpEF+EePH compared with HFpEF (p=0.01). RPB was ≥1-unit higher at 20W and VO_2peak was lower (p<0.01) in HFpEF+EePH compared with HFpEF.</p><p><strong>Conclusions: </strong>These data suggest that EePH contributes to pulmonary gas exchange impairments during exercise by causing a V/Q mismatch that provokes both ventilatory inefficiency and hypoxemia, both of which seem to contribute to DOE and exercise intolerance in patients with HFpEF.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603762","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":"Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French pharmacovigilance database.","authors":"Sophie Yavordios, Guillaume Beltramo, Romane Freppel, Frédérique Beau Salinas, Christine Le Beller, Kevin Bihan, Pierre Mouillot, Marjolaine Georges, Aurélie Grandvuillemin, Philippe Bonniaud","doi":"10.1183/13993003.00756-2024","DOIUrl":"https://doi.org/10.1183/13993003.00756-2024","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung diseases (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through Adverse Drug Reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs.</p><p><strong>Methods: </strong>This retrospective study included cases registered in the FPVD from 1st January 1985 to 1st April 2022 which had ADR coded in MedDRA with a High Level Group Term \"Lower respiratory tract disorders (excluding obstruction and infection)\" involving patients aged 18 and over.</p><p><strong>Results: </strong>We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and in 13.3% death ensued. Men accounted for 54.4% of the cases. Median age was 69 [18-103] years. The most prevalent ADRs were \"ILD\" (51.0%), \"Pulmonary oedema\" (acute/non-acute) (15.6%) and \"Pulmonary fibrosis\" (10.5%). \"Anti-cancer drugs\" (31.2%) and \"Cardiovascular drugs\" (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%).</p><p><strong>Conclusion: </strong>This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify it properly and discontinue the culprit drug urgently.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603723","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":"<i>ERJ</i> Podcast October 2024: World Symposium on Pulmonary Hypertension.","authors":"","doi":"10.1183/13993003.E6404-2024","DOIUrl":"https://doi.org/10.1183/13993003.E6404-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 4","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557507","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":"Exploring the patient perspective in pulmonary hypertension.","authors":"H James Ford, Colleen Brunetti, Pisana Ferrari, Gergely Meszaros, Victor M Moles, Hall Skaara, Adam Torbicki, J Simon R Gibbs","doi":"10.1183/13993003.01129-2024","DOIUrl":"10.1183/13993003.01129-2024","url":null,"abstract":"<p><p>The global impacts of pulmonary hypertension (PH) were formally recognised in 1973 at the 1st World Health Organization meeting dedicated to primary pulmonary hypertension, held in Geneva. Investigations into disease pathogenesis and classification led to the development of numerous therapies over the ensuing decades. While the impacts of the disease have been lessened due to treatments, the symptoms and adverse effects of PH and its therapies on patients' wellbeing and mental health remain significant. As such, there is a critical need to enhance understanding of the challenges patients face on a global scale with respect to care access, multidimensional patient support and advocacy. In addition, thoughtful analysis of the potential benefits and utilisation of mechanisms for the incorporation of patient-reported outcomes into diagnosis and treatment plans is needed. A summary of these areas is included here. We present a report of global surveys of patient and provider experiences and challenges regarding care access and discuss possible solutions. Also addressed is the current state of PH patient associations around the world. Potential ways to enhance patient associations and enable them to provide the utmost support are discussed. A summary of relevant patient-reported outcome measures to assess health-related quality of life in PH is presented, with suggestions regarding incorporation of these tools in patient care and research. Finally, information on how current global threats such as pandemics, climate change and armed conflict may impact PH patients is offered, along with insights as to how they may be mitigated with advanced contingency planning.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105944","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}

{"title":"The Seventh World Symposium on Pulmonary Hypertension: our journey to Barcelona.","authors":"Marc Humbert, Nazzareno Galiè, Lewis J Rubin, Gérald Simonneau, Vallerie V McLaughlin","doi":"10.1183/13993003.01222-2024","DOIUrl":"10.1183/13993003.01222-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105952","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}

{"title":"Chronic thromboembolic pulmonary disease.","authors":"Nick H Kim, Andrea M D'Armini, Marion Delcroix, Xavier Jaïs, Mitja Jevnikar, Michael M Madani, Hiromi Matsubara, Massimiliano Palazzini, Christoph B Wiedenroth, Gérald Simonneau, David P Jenkins","doi":"10.1183/13993003.01294-2024","DOIUrl":"10.1183/13993003.01294-2024","url":null,"abstract":"<p><p>Chronic thromboembolic pulmonary hypertension is a complication of pulmonary embolism and a treatable cause of pulmonary hypertension. The pathology is a unique combination of mechanical obstruction due to failure of clot resolution, and a variable degree of microvascular disease, that both contribute to pulmonary vascular resistance. Accordingly, multiple treatments have been developed to target the disease components. However, accurate diagnosis is often delayed. Evaluation includes high-quality imaging modalities, necessary for disease confirmation and for appropriate treatment planning. All patients with chronic thromboembolic pulmonary disease, and especially those with pulmonary hypertension, should be referred to expert centres for multidisciplinary team decision on treatment. The first decision remains assessment of operability, and the best improvement in symptoms and survival is achieved by the mechanical therapies, pulmonary endarterectomy and balloon pulmonary angioplasty. With the advances in multimodal therapies, excellent outcomes can be achieved with 3-year survival of >90%.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105939","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}

{"title":"Transplantation, bridging, and support technologies in pulmonary hypertension.","authors":"Laurent Savale, Alberto Benazzo, Paul Corris, Shaf Keshavjee, Deborah Jo Levine, Olaf Mercier, R Duane Davis, John T Granton","doi":"10.1183/13993003.01193-2024","DOIUrl":"10.1183/13993003.01193-2024","url":null,"abstract":"<p><p>Despite the progress made in medical therapies for treating pulmonary hypertension (PH), a subset of patients remain susceptible to developing a maladaptive right ventricular phenotype. The effective management of end-stage PH presents substantial challenges, necessitating a multidisciplinary approach and early identification of patients prone to acute decompensation. Identifying potential transplant candidates and assessing the feasibility of such a procedure are pivotal tasks that should be undertaken early in the treatment algorithm. Inclusion on the transplant list is contingent upon a comprehensive risk assessment, also considering the specific type of PH and various factors affecting waiting times, all of which should inform the decision-making process. While bilateral lung transplantation is the preferred option, it demands expert intra- and post-operative management to mitigate the heightened risks of pulmonary oedema and primary graft dysfunction in PH patients. Despite the availability of risk assessment tools, the occurrence of acute PH decompensation episodes can be unpredictable, potentially leading to refractory right ventricular failure even with optimal medical intervention, necessitating the use of rescue therapies. Advancements in right ventricular assist techniques and adjustments to graft allocation protocols for the most critically ill patients have significantly enhanced the survival in intensive care, affording the opportunity to endure while awaiting an urgent transplant. Given the breadth of therapeutic options available, specialised centres capable of delivering comprehensive care have become indispensable for optimising patient outcomes. These centres are instrumental in providing holistic support and management tailored to the complex needs of PH patients, ultimately enhancing their chances of a successful transplant and improved long-term prognosis.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105953","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}

{"title":"Worsening dyspnoea as a predictor of progression of pulmonary fibrosis.","authors":"Marlies S Wijsenbeek, Jeffrey J Swigris, Paolo Spagnolo, Martin Kolb, Michael Kreuter, Hilario Nunes, Wibke Stansen, Klaus B Rohr, Yoshikazu Inoue","doi":"10.1183/13993003.02211-2023","DOIUrl":"10.1183/13993003.02211-2023","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125255","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}

{"title":"Genetics and precision genomics approaches to pulmonary hypertension.","authors":"Eric D Austin, Micheala A Aldred, Mona Alotaibi, Stefan Gräf, William C Nichols, Richard C Trembath, Wendy K Chung","doi":"10.1183/13993003.01370-2024","DOIUrl":"10.1183/13993003.01370-2024","url":null,"abstract":"<p><p>Considerable progress has been made in the genomics of pulmonary arterial hypertension (PAH) since the 6th World Symposium on Pulmonary Hypertension, with the identification of rare variants in several novel genes, as well as common variants that confer a modest increase in PAH risk. Gene and variant curation by an expert panel now provides a robust framework for knowing which genes to test and how to interpret variants in clinical practice. We recommend that genetic testing be offered to specific subgroups of symptomatic patients with PAH, and to children with certain types of group 3 pulmonary hypertension (PH). Testing of asymptomatic family members and the use of genetics in reproductive decision-making require the involvement of genetics experts. Large cohorts of PAH patients with biospecimens now exist and extension to non-group 1 PH has begun. However, these cohorts are largely of European origin; greater diversity will be essential to characterise the full extent of genomic variation contributing to PH risk and treatment responses. Other types of omics data are also being incorporated. Furthermore, to advance gene- and pathway-specific care and targeted therapies, gene-specific registries will be essential to support patients and their families and to lay the foundation for genetically informed clinical trials. This will require international outreach and collaboration between patients/families, clinicians and researchers. Ultimately, harmonisation of patient-derived biospecimens, clinical and omic information, and analytic approaches will advance the field.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105945","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}