Respiratory Research最新文献

{"title":"Identification of progressive pulmonary fibrosis: consensus findings from a modified Delphi study.","authors":"Athol U Wells, Simon L F Walsh, Ayodeji Adegunsoye, Vincent Cottin, Sonye K Danoff, Anand Devaraj, Kevin R Flaherty, Peter M George, Kerri A Johannson, Martin Kolb, Yasuhiro Kondoh, Andrew G Nicholson, Sara Tomassetti, Elizabeth R Volkmann, Kevin K Brown","doi":"10.1186/s12931-024-03070-z","DOIUrl":"10.1186/s12931-024-03070-z","url":null,"abstract":"<p><strong>Background: </strong>We sought consensus among practising respiratory physicians on the prediction, identification and monitoring of progression in patients with fibrosing interstitial lung disease (ILD) using a modified Delphi process.</p><p><strong>Methods: </strong>Following a literature review, statements on the prediction, identification and monitoring of progression of ILD were developed by a panel of physicians with specialist expertise. Practising respiratory physicians were sent a survey asking them to indicate their level of agreement with these statements on a binary scale or 7-point Likert scale (- 3 to 3), or to select answers from a list. Consensus was considered to be achieved if ≥ 70% of respondents selected the same answer, or, for responses on a Likert scale, the median score was ≤ -2 (disagree/not important) or ≥ 2 (agree/important) with an interquartile range ≤ 1. There were three rounds of the survey.</p><p><strong>Results: </strong>Surveys 1, 2 and 3 were completed by 207, 131 and 94 physicians, respectively, between March 2022 and July 2023. Decline in forced vital capacity (FVC), decline in diffusing capacity of the lungs for carbon monoxide, and increased fibrosis on high-resolution computed tomography (HRCT) were ranked as the most important endpoints for determining progression. Consensus was reached that progression on HRCT or a decline in FVC ≥ 10% from baseline is sufficient to determine progression, and that small declines in multiple endpoints indicates progression. Consensus was reached that a histological pattern of usual interstitial pneumonia (UIP) is a risk factor for progression of ILD, but that a biopsy to look for a UIP pattern should not be performed solely for prognostic reasons. Consensus was not reached on the time period over which progression should be defined. There was consensus that appropriate management of ILD depends on the type of ILD, and that 'despite adequate management' or 'despite usual management' should be included in the definition of progression.</p><p><strong>Conclusions: </strong>This modified Delphi process provided consensus statements on the identification of ILD progression that were supported by a broad group of clinicians and may help to inform clinical practice until robust evidence-based guidelines are available.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"448"},"PeriodicalIF":5.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in initial pharmacological COPD treatment in primary care (2010-2021): a population-based study using the PHARMO Data Network.","authors":"Guilherme Rodrigues, Joana Antão, Qichen Deng, Brenda N Baak, Alda Marques, Frits M E Franssen, Martijn A Spruit","doi":"10.1186/s12931-024-03073-w","DOIUrl":"10.1186/s12931-024-03073-w","url":null,"abstract":"<p><strong>Background: </strong>Pharmacological treatment is a cornerstone of chronic obstructive pulmonary disease (COPD) management, with general practitioners providing the most care. However, the lack of data on prescribing trends in initial pharmacotherapy in primary care hinders the understanding of how scientific and technical developments impact patient care and may also perpetuate suboptimal practices. Hence, this study aims to analyze trends in the initial pharmacological treatment of newly diagnosed COPD patients in Dutch primary care from 2010 to 2021.</p><p><strong>Methods: </strong>A repeated cross-sectional study was conducted via the PHARMO GP Database. Data were extracted from the electronic health records of individuals managed by general practitioners in the Netherlands within the PHARMO Data Network. Individuals aged ≥ 40 years at diagnosis with an International Classification of Primary Care code for COPD (R95) were included. Initial pharmacological treatment was identified based on the first prescription issued within 90 days postdiagnosis. The annual proportions of individuals receiving a specific treatment among those diagnosed were calculated and directly standardized by age and sex according to the 2021 Dutch population structure. Trend analysis was performed via joinpoint regression.</p><p><strong>Results: </strong>A total of 54,628 COPD patients were included (median [IQR] age: 65 [57-73]; 53.7% male), with 36.4% not receiving respiratory medication within 90 days of diagnosis, and 4.2% on other treatments. Trend analysis revealed that LAMA monotherapy increased from 13.4% in 2010 to 15.1% in 2015 and then declined to 11.0% by 2021. Moreover, LABA-ICS decreased from 17.6% to 8.5% between 2010 and 2018, after which it plateaued. In contrast, LABA-LAMA sharply increased, from 0.6% in 2010 to 9.6% in 2021. LABA monotherapy increased from 2.6% in 2010 to 5.7% in 2021. Triple therapy has remained constant. For reliever-only therapies, SABA increased from 8.5% in 2010 to 14.3% in 2018 and then stabilized, whereas SAMA and SABA-SAMA remained low throughout.</p><p><strong>Conclusions: </strong>Shifts in initial pharmacological COPD treatment from 2010 to 2021 likely reflect the introduction of new inhalers and updated management strategies. However, a significant proportion of patients remain without GP prescriptions, which warrants further investigation.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"447"},"PeriodicalIF":5.8,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gas transport mechanisms during high-frequency ventilation.","authors":"Thomas J A Scott, Chinthaka Jacob, David G Tingay, Justin S Leontini","doi":"10.1186/s12931-024-03049-w","DOIUrl":"10.1186/s12931-024-03049-w","url":null,"abstract":"<p><p>By virtue of applying small tidal volumes, high-frequency ventilation is advocated as a method of minimizing ventilator-induced lung injury. Lung protective benefits are established in infants, but not in other patient cohorts. Efforts to improve and extend the lung protection potential should consider how fundamental modes of gas transport can be exploited to minimize harmful tidal volumes while maintaining or improving ventilation.This research investigates different models of gas transport during high-frequency ventilation and discusses the extent to which the gas transport mechanisms are considered in each. The research focuses on the rationale for current ventilation protocols, how they were informed by these models, and investigates alternative protocols that may improve gas transport and lung protection. A review of high-frequency ventilation physiology and fluid mechanics literature was performed, and dimensional analyses were conducted showing the relationship between clinical data and the model outputs. We show that contemporary protocols have been informed by resistor-inductor-capacitor, or network, models of the airway-lung system that are formulated around a ventilation pressure cost framework. This framework leads to clinical protocol selection that ventilates patients at frequencies that excite a resonance in the lung. We extend on these models by considering frequencies that are much higher than resonance which further optimize gas transport in the airway via alternative gas transport mechanisms to bulk advection that operate for very low tidal volumes. Our findings suggest it is unlikely that gas transport is optimally exploited during current approaches to high-frequency ventilation and protocols that differ significantly from those currently in use could achieve ventilation while using very low tidal volumes.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"446"},"PeriodicalIF":5.8,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11682653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-induced bronchoconstriction in children: Delphi study and consensus document about definition and epidemiology, diagnostic work-up, treatment, and follow-up.","authors":"Valentina Fainardi, Roberto Grandinetti, Nicole Mussi, Arianna Rossi, Marco Masetti, Antonella Giudice, Simone Pilloni, Michela Deolmi, Greta Ramundo, Stefano Alboresi, Barbara Maria Bergamini, Andrea Bergomi, Maria Teresa Bersini, Loretta Biserna, Paolo Bottau, Elena Corinaldesi, Sara Crestani, Nicoletta De Paulis, Simone Fontijn, Battista Guidi, Francesca Lombardi, Lanfranco Loretano, Paola Gallo, Fabio Guerrera, Sandra Mari, Francesca Marotti, Angela Miniaci, Marco Parpanesi, Silvia Pastorelli, Alessandra Piccorossi, Carlotta Povesi Dascola, Lamberto Reggiani, Roberto Sacchetti, Valeria Scialpi, Francesca Vaienti, Cristina Venturelli, Lucia Vignutelli, Giampaolo Ricci, Carlo Caffarelli, Susanna Esposito","doi":"10.1186/s12931-024-03078-5","DOIUrl":"10.1186/s12931-024-03078-5","url":null,"abstract":"<p><strong>Background: </strong>Exercise-induced bronchoconstriction (EIB) is common in children with asthma but can be present also in children without asthma, especially athletes. Differential diagnosis includes several conditions such as exercise-induced laryngeal obstruction (EILO), cardiac disease, or physical deconditioning. Detailed medical history, clinical examination and specific tests are mandatory to exclude alternative diagnoses. Given the high prevalence of EIB in children and its potential impact on health, sport performance, and daily levels of physical activity, health care professionals should be aware of this condition and able to provide a specific work-up for its identification. The aims of the present study were: (a) to assess the agreement among hospital pediatricians and primary care pediatricians of Emilia-Romagna Region (Italy) about the management of EIB in children and (b) formulate statements in a consensus document to help clinicians in daily clinical practice.</p><p><strong>Methods: </strong>According to Delphi method, a panel of specialists scored 40 statements that were then revised and discussed during online meetings to reach full consensus. Statements were then formulated.</p><p><strong>Results: </strong>To obtain full consensus, the questionnaire was administered in two rounds after full discussion of the uncertain topics on the basis of the latest evidence on EIB published over the last 10 years. Despite an overall agreement on EIB management, some gaps emerged in the sections dedicated to diagnosis and treatment. Nine summary statements on definition, pathogenesis, diagnostic work-up, treatment, and follow-up were eventually formulated.</p><p><strong>Conclusions: </strong>This study describes the knowledge of EIB in a group of pediatricians and highlights gaps and uncertainties in diagnosis and treatment. The creation of statements shared by the specialists of the same area may improve the management of EIB in children. However, more research and evidence are needed to better clarify the best treatment and to standardize the best diagnostic protocol limiting useless examinations but at the same time assuring the best management.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"445"},"PeriodicalIF":5.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in muscle-to-fat ratio are associated with lung function decline and airflow obstruction in the general population.","authors":"Eunwoo Kim, Ah Young Leem, Ji Ye Jung, Young Sam Kim, Youngmok Park","doi":"10.1186/s12931-024-03081-w","DOIUrl":"10.1186/s12931-024-03081-w","url":null,"abstract":"<p><strong>Background: </strong>The long-term relationship between body composition and lung function has not yet been fully demonstrated. We investigated the longitudinal association between muscle-to-fat (MF) ratio and lung function among middle-aged general population.</p><p><strong>Methods: </strong>Participants were enrolled from a community-based prospective cohort between 2005 and 2014. Lung function parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV₁], and FEV₁/FVC) and the MF ratio (total body muscle mass [kg]/fat mass [kg]) were assessed biannually via spirometry and bioelectrical impedance analysis, respectively.</p><p><strong>Results: </strong>We followed up 4,712 participants (age 53.9 ± 7.9 years, men 45.8%) for 8 years. With an increase in MF ratio of 1, in men, the FVC increased by 43.9 mL, FEV₁ by 37.6 mL, and FEV₁/FVC by 0.320%, while in non-smoking women, the FVC increased by 55.8 mL, FEV₁ by 44.3 mL, and FEV₁/FVC by 0.265% (all P < 0.001). The MF ratio-decreased group showed further annual deterioration in lung function than the MF ratio-increased group (men: FVC - 44.1 mL vs. -28.4 mL, FEV₁ -55.8 mL vs. -39.7 mL, FEV₁/FVC - 0.53% vs. -0.42%; non-smoking women: FVC - 34.2 mL vs. -30.3 mL, FEV₁ -38.0 mL vs. -35.2 mL; all P < 0.001, except FEV₁ in non-smoking women; P = 0.005). The odds ratio for the incidence of airflow obstruction according to the MF ratio was 0.77 (95% CI, 0.68-0.87) in men and 0.85 (95% CI, 0.74-0.97) in non-smoking women.</p><p><strong>Conclusions: </strong>Long-term changes in the MF ratio are related to lung function deterioration and incidence of airflow obstruction in middle-aged general population.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"444"},"PeriodicalIF":5.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activated DRP1 promotes mitochondrial fission and induces glycolysis in ATII cells under hyperoxia.","authors":"Tong Sun, Haiyang Yu, Dingning Zhang, Danni Li, Jianhua Fu","doi":"10.1186/s12931-024-03083-8","DOIUrl":"10.1186/s12931-024-03083-8","url":null,"abstract":"<p><strong>Backgroud: </strong>Recent studies have reported mitochondrial damage and metabolic dysregulation in BPD, but the changes in mitochondrial dynamics and glucose metabolic reprogramming in ATII cells and their regulatory relationship have not been reported.</p><p><strong>Methods: </strong>Neonatal rats in this study were divided into model (FIO2:85%) and control (FIO2: 21%) groups. Lung tissues were extracted at 3, 7, 10 and 14 postnatal days and then conducted HE staining for histopathological observation. We assessed the expression of mitochondria dynamic associated proteins and glycolysis associated enzymes in lung tissues, primary ATII cells and RLE-6TN cells. Double immunofluorescence staining was used to confirm the co-localization of DRP1 and ATII cells. Real-time analyses of ECAR and OCR were performed with primary ATII cells using Seahorse XF96. ATP concentration was measured using an ATP kit. We treated RLE-6TN cells at 85% hyperoxia for 48 h with mitochondrial fission inhibitor Mdivi-1 to verify the role of DRP1 in regulating glucose metabolic reprogramming.</p><p><strong>Findings: </strong>We found that hyperoxia causes ATII cells' mitochondrial morphological change. The expression of DRP1 and p-DRP1 increased in lung tissue and primary ATII cells of neonatal rats exposed to hyperoxia. Glycolysis related enzymes including PFKM, HK2, and LDHA were also increased. Hyperoxia inhibited ATP production in ATII cells. In RLE-6TN cells, we verified that the administration of Mdivi-1 could alleviate the enhancement of aerobic glycolysis and fragmentation of mitochondria caused by hyperoxia.</p><p><strong>Interpretations: </strong>Hyperoxia exposure leads to increased mitochondrial fission in ATII cells and mediates the reprogramming of glucose metabolism via the DRP1 signaling pathway. Inhibiting the activation of DRP1 signaling pathway may be a promising therapeutic target for BPD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"443"},"PeriodicalIF":5.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferritinophagy mediated by the AMPK/ULK1 pathway is involved in ferroptosis subsequent to ventilator-induced lung injury.","authors":"Huajin Ou, Jinyuan Lin, Liu Ji, Liu Ye, Maoyao Ling, Xiaoting Liao, Fei Lin, Yuqing Wang, Bijun Luo, Zhaokun Hu, Linghui Pan","doi":"10.1186/s12931-024-03076-7","DOIUrl":"10.1186/s12931-024-03076-7","url":null,"abstract":"<p><p>Mechanical ventilation (MV) remains a cornerstone of critical care; however, its prolonged application can exacerbate lung injury, leading to ventilator-induced lung injury (VILI). Although previous studies have implicated ferroptosis in the pathogenesis of VILI, the underlying mechanisms remain unclear. This study investigated the roles of ferritinophagy in ferroptosis subsequent to VILI. Using C57BL/6J mice and MLE-12 cells, we established both in vivo and in vitro models of VILI and cyclic stretching (CS)-induced cellular injury. We assessed lung injury and the biomarkers of ferroptosis and ferritinophagy, after appropriate pretreatments. This study demonstrated that high tidal volumes (HTV) for 4 h enhanced the sensitivity to ferroptosis in both models, evidenced by increased intracellular iron levels, lipid peroxidation and cell death, which can be mitigated by ferrostatin-1 treatment. Notably, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy contributed to ferroptosis in VILI. Inhibition of autophagy with 3-methyladenine or NCOA4 knockdown decreased intracellular Fe²⁺ levels and inhibited lipid peroxidation, thereby attenuating CS-induced lung injury. Furthermore, it has also been observed that the AMPK/ULK1 axis can trigger ferritinophagy in VILI. Collectively, our study indicated that MV can induce ferroptosis by promoting NCOA4-dependent ferritinophagy, which could be a novel therapeutic target for the prevention and treatment of VILI.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"440"},"PeriodicalIF":5.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bronchoscopic biopsies - a novel source for primary airway epithelial cells in respiratory research.","authors":"Kimberly Barbet, Mona S Schmitz, Dirk Westhölter, Markus Kamler, Stephan Rütten, Anja L Thiebes, Barbara Sitek, Malte Bayer, Michaela Schedel, Sebastian Reuter, Kaid Darwiche, Anja E Luengen, Christian Taube","doi":"10.1186/s12931-024-03060-1","DOIUrl":"10.1186/s12931-024-03060-1","url":null,"abstract":"<p><strong>Background: </strong>Using primary airway epithelial cells (AEC) is essential to mimic more closely different types and stages of lung disease in humans while reducing or even replacing animal experiments. Access to lung tissue remains limited because these samples are generally obtained from patients who undergo lung transplantation for end-stage lung disease or thoracic surgery for (mostly) lung cancer. We investigated whether forceps or cryo biopsies are a viable alternative source of AEC compared to the conventional technique.</p><p><strong>Methods: </strong>AECs were obtained ex vivo from healthy donor lung tissue using the conventional method and two biopsy procedures (forceps, cryo). The influence of the isolation method on the quality and function of AEC was investigated at different time-points during expansion and differentiation in air-liquid interface cultures. In addition, fully-differentiated AECs were stimulated with house dust mite extract (HDM) to allow functional analyses in an allergic in vitro model. Vitality or differentiation capacity were determined using flow cytometry, scanning electron microscope, periodic acid-Schiff reaction, immunofluorescence staining, and proteomics.</p><p><strong>Results: </strong>As anticipated, no significant differences between each of the sampling methods were detected for any of the measured outcomes. The proteome composition was comparable for each isolation method, while donor-dependent effects were observed. Treatment with HDM led to minor differences in mucociliary differentiation.</p><p><strong>Conclusions: </strong>Our findings confirmed the adequacy of these alternative approaches for attaining primary AECs, which can now expand the research for a broader range of lung diseases and for studies at an earlier stage not requiring lung surgery.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"439"},"PeriodicalIF":5.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of a composite physiologic index developed by adding bronchial and hyperlucent volumes quantified via artificial intelligence technology.","authors":"Michihiro Uyama, Tomohiro Handa, Ryuji Uozumi, Seishu Hashimoto, Yoshio Taguchi, Kohei Ikezoe, Kiminobu Tanizawa, Naoya Tanabe, Tsuyoshi Oguma, Atsushi Matsunashi, Takafumi Niwamoto, Hiroshi Shima, Ryobu Mori, Tomoki Maetani, Yusuke Shiraishi, Tomomi W Nobashi, Ryo Sakamoto, Takeshi Kubo, Akihiko Yoshizawa, Kazuhiro Terada, Yuji Nakamoto, Toyohiro Hirai","doi":"10.1186/s12931-024-03075-8","DOIUrl":"10.1186/s12931-024-03075-8","url":null,"abstract":"<p><strong>Background: </strong>The composite physiologic index (CPI) was developed to estimate the extent of interstitial lung disease (ILD) in idiopathic pulmonary fibrosis (IPF) patients based on pulmonary function tests (PFTs). The CALIPER-revised version of the CPI (CALIPER-CPI) was also developed to estimate the volume fraction of ILD measured by CALIPER, an automated quantitative CT postprocessing software. Recently, artificial intelligence-based quantitative CT image analysis software (AIQCT), which can be used to quantify the bronchial volume separately from the ILD volume, was developed and validated in IPF. The aim of this study was to develop AIQCT-derived CPI formulas to quantify CT abnormalities in IPF and to investigate the associations of these CPI formulas with survival.</p><p><strong>Methods: </strong>The first cohort included 116 patients with IPF. In this cohort, ILD, bronchial, and hyperlucent volumes on CT were quantified using AIQCT. New CPI formulas were developed based on PFTs to estimate the volume fraction of ILD (ILD-CPI), the sum of the ILD and bronchial volume fractions (ILDB-CPI), and the sum of the ILD, bronchial and hyperlucent volume fractions (ILDBH-CPI). The associations of the original CPI, the CALIPER-CPI and the AIQCT-derived CPIs with survival were analyzed in the first cohort and in a second cohort of patients with IPF (n = 72).</p><p><strong>Results: </strong>In the first cohort, over a median observation time of 92.8 months, 79 patients (68.1%) died, and one patient (0.9%) underwent living-donor lung transplantation. The original CPI, the CALIPER-CPI, and all AIQCT-derived CPIs were associated with overall survival (hazard ratios: 1.07-1.22). The C-index of the ILDB-CPI (0.759) was the highest among all AIQCT-derived CPIs and was comparable to that of the original CPI (0.765) and the CALIPER-CPI (0.749). The C-index of the ILDBH-CPI (0.729) was lower than that of the other CPI variables. The second cohort yielded similar C-indices as the first cohort for the original CPI (0.738), CALIPER-CPI (0.757) and ILDB-CPI (0.749).</p><p><strong>Conclusions: </strong>The ILDB-CPI can predict the outcomes of IPF patients with a similar performance to that of the original CPI and the CALIPER-CPI. Adding the hyperlucent volume to the CPI formula did not improve its predictive accuracy for mortality.</p><p><strong>Trial registration: </strong>None (no health care interventions were performed).</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"442"},"PeriodicalIF":5.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CTSS contributes to airway neutrophilic inflammation in mixed granulocytic asthma.","authors":"Haixiong Tang, Zhongli Li, Changyun Yang, Lin Fu, Xiaolong Ji, Zemin Chen, Sudan Gan, Hailing Zhang, PingAn Zhang, Shiyue Li, Wenjun Zhang, Xin Chen, Lihong Yao, Jing Li","doi":"10.1186/s12931-024-03077-6","DOIUrl":"10.1186/s12931-024-03077-6","url":null,"abstract":"<p><strong>Background: </strong>Mixed granulocytic asthma (MGA) is usually associated with poor response to corticosteroid therapy and a high risk of severe asthma. Cathepsin S (CTSS) has been found to play an important role in various inflammatory diseases. This study was aimed to investigate the role of CTSS in MGA.</p><p><strong>Methods: </strong>Induced sputum was obtained from healthy subjects and asthma patients. Two murine models of MGA were established using either TDI (toluene diisocyanate) alone or OVA emulsified in CFA. LY3000328, a specific antagonist of CTSS, was therapeutically given to BALB/c mice after airway challenge with TDI or OVA. The effects of recombinant CTSS was tested in vivo, and Akt inhibition was used to explore a possible mechanism for CTSS-induced airway inflammation.</p><p><strong>Results: </strong>MGA patients have a significant higher sputum CTSS level than the health and subjects with other inflammatory phenotypes, which was positively correlated with sputum level of soluble E-cadherin (sE-cadherin), sputum neutrophils, FeNO, FEF25-75% and glucocorticoid dosage. Allergen exposure markedly increased CTSS level and pharmacological antagonism of CTSS with LY3000328 decreased airway hyperresponsiveness, airway neutrophil accumulation, as well as the release of IL-17 and sE-cadherin in murine models of MGA, yet had no effects on eosinophilic inflammation nor type 2 inflammatory cytokines (IL-4 and IL-5). In addition, intratracheal instillation of recombinant CTSS leads to neutrophil recruitment and overproduction of sE-cadherin in the lung tissues, which could be attenuated by inhibition of Akt signaling.</p><p><strong>Conclusion: </strong>Our data suggested that CTSS contributes to airway neutrophilic inflammation in MGA through an Akt-dependent pathway.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"441"},"PeriodicalIF":5.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}