Lung最新文献

{"title":"The Synthetic Surfactant CHF5633 Restores Lung Function and Lung Architecture in Severe Acute Respiratory Distress Syndrome in Adult Rabbits","authors":"Pavol Mikolka, Petra Kosutova, Maros Kolomaznik, Nikolett Nemcova, Juliana Hanusrichterova, Tore Curstedt, Jan Johansson, Andrea Calkovska","doi":"10.1007/s00408-024-00689-z","DOIUrl":"https://doi.org/10.1007/s00408-024-00689-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults. In ARDS extensive inflammation and leakage of fluid into the alveoli lead to dysregulation of pulmonary surfactant metabolism and function. Altered surfactant synthesis, secretion, and breakdown contribute to the clinical features of decreased lung compliance and alveolar collapse. Lung function in ARDS could potentially be restored with surfactant replacement therapy, and synthetic surfactants with modified peptide analogues may better withstand inactivation in ARDS alveoli than natural surfactants.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study aimed to investigate the activity in vitro and the bolus effect (200 mg phospholipids/kg) of synthetic surfactant CHF5633 with analogues of SP‐B and SP‐C, or natural surfactant Poractant alfa (Curosurf^®, both preparations Chiesi Farmaceutici S.p.A.) in a severe ARDS model (the ratio of partial pressure arterial oxygen and fraction of inspired oxygen, <i>P/F</i> ratio ≤ 13.3 kPa) induced by hydrochloric acid instillation followed by injurious ventilation in adult New Zealand rabbits. The animals were ventilated for 4 h after surfactant treatment and the respiratory parameters, histological appearance of lung parenchyma and levels of inflammation, oxidative stress, surfactant dysfunction, and endothelial damage were evaluated.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Both surfactant preparations yielded comparable improvements in lung function parameters, reductions in lung injury score, pro-inflammatory cytokines levels, and lung edema formation compared to untreated controls.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This study indicates that surfactant replacement therapy with CHF5633 improves lung function and lung architecture, and attenuates inflammation in severe ARDS in adult rabbits similarly to Poractant alfa. Clinical trials have so far not yielded conclusive results, but exogenous surfactant may be a valid supportive treatment for patients with ARDS given its anti-inflammatory and lung-protective effects.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"17 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutralization of CX3CL1 Attenuates TGF-β-Induced Fibroblast Differentiation Through NF-κB Activation and Mitochondrial Dysfunction in Airway Fibrosis","authors":"Wun-Hao Cheng, Pao-Lung Chang, Yu-Chih Wu, Shao-An Wang, Chia-Ling Chen, Feng-Lin Hsu, Mei-May Neoh, Lee-Yuan Lin, Fara Silvia Yuliani, Chien-Huang Lin, Bing-Chang Chen","doi":"10.1007/s00408-024-00701-6","DOIUrl":"https://doi.org/10.1007/s00408-024-00701-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Severe asthma, characterized by inflammation and airway remodeling, involves fibroblast differentiation into myofibroblasts expressing α-SMA. This process leads to the production of fibronectin and connective tissue growth factor (CTGF), driven by factors such as transforming growth factor (TGF)-β. Furthermore, the persistent presence of myofibroblasts is associated with resistance to apoptosis and mitochondrial dysfunction. The chemokine (C-X3-C motif) ligand 1 (CX3CL1) plays a role in tissue fibrosis. However, it is currently unknown whether neutralization of CX3CL1 decreases TGF-β-induced fibroblast differentiation and mitochondrial dysfunction in normal human lung fibroblasts (NHLFs).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>CX3CL1/C-X3-C motif chemokine receptor 1 (CX3CR1), CX3CL1 was analyzed by immunofluorescence (IF) or immunohistochemical (IHC) staining of ovalbumin-challenged mice. CX3CL1 release was detected by ELISA. TGF-β-induced CTGF, fibronectin, and α-SMA expression were evaluated in NHLFs following neutralization of CX3CL1 (TP213) treatment for the indicated times by Western blotting or IF staining. Mitochondrion function was detected by a JC-1 assay and seahorse assay. Cell apoptosis was observed by a terminal uridine nick-end labeling (TUNEL) assay.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>An increase in CX3CL1 expression was observed in lung tissues from mice with ovalbumin-induced asthma by IF staining. CX3CR1 was increased in the subepithelial layer of the airway by IHC staining. Moreover, CX3CR1 small interfering (si)RNA downregulated TGF-β-induced CTGF and fibronectin expression in NHLFs. CX3CL1 induced CTGF and fibronectin expression in NHLFs. TGF-β-induced CX3CL1 secretion from NHLFs. Furthermore, TP213 decreased TGF-β-induced CTGF, fibronectin, and α-SMA expression in NHLFs. Mitochondrion-related differentially expressed genes (DEGs) were examined after CX3CL1 neutralization in TGF-β-treated NHLFs. TP213 alleviated TGF-β-induced mitochondrial dysfunction and apoptosis resistance in NHLFs. CX3CL1 induced p65, IκBα, and IKKα phosphorylation in a time-dependent manner. Furthermore, CX3CL1-induced fibronectin expression and JC-1 monomer were decreased by p65 siRNA. TP213 reduced TGF-β-induced p65 and α-SMA expression in NHLFs.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These findings suggest that neutralizing CX3CL1 attenuates lung fibroblast activation and mitochondrial dysfunction. Understanding the impacts of CX3CL1 neutralization on fibroblast mitochondrial function could contribute to the development of therapeutic strategies for managing airway remodeling in severe asthma.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"101 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoprotegerin is an Early Marker of the Fibrotic Process and of Antifibrotic Treatment Responses in Ex Vivo Lung Fibrosis","authors":"Kurnia S. S. Putri, Adhyatmika Adhyatmika, Carian E. Boorsma, Habibie Habibie, Mitchel J. R. Ruigrok, Peter Heukels, Wim Timens, Marina H. de Jager, Wouter L. J. Hinrichs, Peter Olinga, Barbro N. Melgert","doi":"10.1007/s00408-024-00691-5","DOIUrl":"https://doi.org/10.1007/s00408-024-00691-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Lung fibrosis is a chronic lung disease with a high mortality rate with only two approved drugs (pirfenidone and nintedanib) to attenuate its progression. To date, there are no reliable biomarkers to assess fibrosis development and/or treatment effects for these two drugs. Osteoprotegerin (OPG) is used as a serum marker to diagnose liver fibrosis and we have previously shown it associates with lung fibrosis as well.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Here we used murine and human precision-cut lung slices to investigate the regulation of OPG in lung tissue to elucidate whether it tracks with (early) fibrosis development and responds to antifibrotic treatment to assess its potential use as a biomarker.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>OPG mRNA expression in murine lung slices was higher after treatment with profibrotic cytokines TGFβ1 or IL13, and closely correlated with Fn and PAI1 mRNA expression. More OPG protein was released from fibrotic human lung slices than from the control human slices and from TGFβ1 and IL13-stimulated murine lung slices compared to control murine slices. This OPG release was inhibited when murine slices were treated with pirfenidone or nintedanib. OPG release from human fibrotic lung slices was inhibited by pirfenidone treatment.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>OPG can already be detected during the early stages of fibrosis development and responds, both in early- and late-stage fibrosis, to treatment with antifibrotic drugs currently on the market for lung fibrosis. Therefore, OPG should be further investigated as a potential biomarker for lung fibrosis and a potential surrogate marker for treatment effect.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"127 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat-Induced Secretion of Heat Shock Proteins 70 and 90 Does not Affect the Expression of the Glucocorticoid Receptor in Primary Airway Cells in COPD","authors":"Liang Zhou, Lei Fang, Michael Roth, Eleni Papakonstantinou, Michael Tamm, Daiana Stolz","doi":"10.1007/s00408-024-00680-8","DOIUrl":"https://doi.org/10.1007/s00408-024-00680-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>The response to glucocorticoids is hampered in many COPD patients by a yet unknown mechanism. Earlier we reported that short-term heat exposure of primary human bronchial epithelial cells (BEC) and airway smooth muscle cells (ASMC) of asthma patients increased the expression and secretion of extracellular heat shock proteins (eHSPs) resulting in increased expression of glucocorticoid receptor (GR) in BEC and inhibition of ASMC remodeling. The aim of the present study was to assess if the same mechanism is also present in primary airway wall cells of COPD patients.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Primary BEC and ASMC were established from endobronchial biopsies obtained from COPD patients (<i>n</i> = 73), who participated in the HISTORIC study, an investigator-initiated and driven clinical trial. Secretion and protein expression of HSPs was assessed by ELISA and Western blotting. Expression of total GR, its isoforms GRα and GRβ and toll-like receptor 4 (TLR4) was determined by Western-blotting.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Short heat exposure (65 °C, 10 s) of BEC resulted in a significant increase of the secretion of eHSP70 and eHSP90, while the intracellular protein was not altered. Heat treatment or exposure to eHSP70 or eHSP90 had no effect on the expression of GR and GR-isoforms. However, eHSP70 and eHSP90 significantly reduced the expression of TLR4.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The results of this study indicate that primary airway cells from COPD patients respond differently to heat exposure and extracellular HSP70 or HSP90 than cells from asthma patients regarding the expression of GR and this may explain the reduced response to glucocorticoids in patients with COPD.</p><p><i>Trial Registration</i>: ISRCTN11017699</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"101 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and PD-L1 Yields","authors":"Lara M. Khoury, Kristin N. Sheehan, William I. Mariencheck, Katherine A. Gershner, Matthew Maslonka, Angela G. Niehaus, Scott Isom, Christina R. Bellinger","doi":"10.1007/s00408-024-00692-4","DOIUrl":"https://doi.org/10.1007/s00408-024-00692-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Immunotherapy is a leading approach for treating advanced non-small cell lung cancer (NSCLC) by targeting the PD-1/PD-L1 checkpoint signaling pathway, particularly in tumors expressing high levels of PD-L1 (Jug et al. in J Am Soc Cytopathol 9:485–493, 2020; Perrotta et al. in Chest 158: 1230–1239, 2020). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method to obtain tissue for molecular studies, including PD-L1 analysis, in unresectable tumors (Genova et al. in Front Immunol 12: 799455, 2021; Wang et al. in Ann Oncol 29: 1417–1422, 2018). This study aimed to assess the adequacy of PD-L1 assessment in EBUS-TBNA cytology specimens.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Data was collected retrospectively from patients who underwent EBUS-TBNA between 2017 and 2021 for suspected lung cancer biopsy. Samples positive for NSCLC were examined for PD-L1 expression. EBUS was performed by experienced practitioners, following institutional guidelines of a minimum of five aspirations from positively identified lesions. Sample adequacy for molecular testing was determined by the pathology department.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The analysis involved 387 NSCLC cases (149 squamous cell, 191 adenocarcinoma, 47 unspecified). Of the 263 EBUS-TBNA specimens tested for PD-L1, 237 (90.1%) were deemed adequate. While 84% adhered to the protocol, adherence did not yield better results. Significantly higher PD-L1 adequacy was observed in squamous cell carcinomas (93.2%) compared to adenocarcinoma (87.6%). The number of aspirations and sedation type did not correlate with PD-L1 adequacy in either cancer type, but lesion size and location had a significant impact in adenocarcinomas. Adenocarcinoma exhibited higher PD-L1 expression (68%) compared to squamous cell carcinoma (48%).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>EBUS-TBNA offers high yields for assessing immunotherapy markers like PD-L1, with satisfactory adequacy regardless of NSCLC subtype, lesion size, or location.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"17 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: Genetic Association of Circulating Adipokines with Risk of Idiopathic Pulmonary Fibrosis: A Two‑Sample Mendelian Randomization Study","authors":"Youqian Zhang, Qiong Wen, Li Li","doi":"10.1007/s00408-024-00687-1","DOIUrl":"https://doi.org/10.1007/s00408-024-00687-1","url":null,"abstract":"","PeriodicalId":18163,"journal":{"name":"Lung","volume":"885 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Spectrum and Clinical Characteristics of Patients with Primary Ciliary Dyskinesia: a Belgian Single Center Study","authors":"Noelia Rodriguez Mier, Martine Jaspers, Evelien Van Hoof, Mark Jorissen, Natalie Lorent, Marijke Proesmans, François Vermeulen, Jeroen Breckpot, Mieke Boon","doi":"10.1007/s00408-024-00696-0","DOIUrl":"https://doi.org/10.1007/s00408-024-00696-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>We aimed to examine the correlation between clinical characteristics and the pathogenic gene variants in patients with Primary Ciliary Dyskinesia (PCD).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We conducted a retrospective single-center study in patients with PCD followed at the University Hospitals Leuven. We included patients with genetically confirmed PCD and described their genotype, data from ultrastructural ciliary evaluation and clinical characteristics. Genotype/phenotype correlations were studied in patients with the most frequently involved genes.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We enrolled 74 patients with a median age of 25.58 years. The most frequently involved genes were <i>DNAH11</i> (n = 23) and <i>DNAH5</i> (n = 19). The most frequent types of pathogenic variants were missense (n = 42) and frameshift variants (n = 36) and most patients had compound heterozygous variants (n = 44). Ciliary ultrastructure (p &lt; 0.001), situs (p = 0.015) and age at diagnosis (median 9.50 vs 4.71 years, p = 0.037) differed between <i>DNAH11</i> and <i>DNAH5</i>. When correcting for situs this difference in age at diagnosis was no longer significant (p = 0.973). Patients with situs inversus were diagnosed earlier (p = 0.031). Respiratory tract microbiology (p = 0.161), lung function (cross-sectional, p = 0.829 and longitudinal, p = 0.329) and chest CT abnormalities (p = 0.202) were not significantly different between <i>DNAH11</i> and <i>DNAH5</i> variants.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study suggests a genotype–phenotype correlation for some of the evaluated clinical characteristics of the two most frequently involved genes in this study, namely <i>DNAH11</i> and <i>DNAH5</i>.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"212 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pressure Support Ventilation Versus T-piece as Spontaneous Breathing Trials for Extubation of Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.","authors":"Luiza Mendes Fonseca, Pedro Matos da Câmara, Iane Miguel Pereira Lettieri, Caroline Serafim Dagostin, Arthur Oswaldo de Abreu Vianna","doi":"10.1007/s00408-024-00678-2","DOIUrl":"10.1007/s00408-024-00678-2","url":null,"abstract":"<p><strong>Background: </strong>Weaning patients with COPD from mechanical ventilation (MV) presents a challenge, as literature on this topic is limited. This study compares PSV and T-piece during spontaneous breathing trials (SBT) in this specific population.</p><p><strong>Methods: </strong>A search of PubMed, EMBASE, and Cochrane in September 2023 yielded four randomized controlled trials (RCTs) encompassing 560 patients. Among these, 287 (51%) used T-piece during SBTs.</p><p><strong>Results: </strong>The PSV group demonstrated a significant improvement in the successful extubation rate compared to the T-piece (risk ratio [RR] 1.14; 95% confidence interval [CI] 1.03-1.26; p = 0.02). Otherwise, there was no statistically significant difference in the reintubation (RR 1.07; 95% CI 0.79-1.45; p = 0.67) or the ICU mortality rates (RR 0.99; 95% CI 0.63-1.55; p = 0.95).</p><p><strong>Conclusion: </strong>Although PSV in SBTs exhibits superior extubation success, consistent weaning protocols warrant further exploration through additional studies.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"211-216"},"PeriodicalIF":4.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.","authors":"Ji-Yoon Oh, Sung-Yoon Kang, Noeul Kang, Ha-Kyeong Won, Eun-Jung Jo, Seung-Eun Lee, Ji-Hyang Lee, Ji-Su Shim, Young-Chan Kim, Youngsang Yoo, Jin An, Hwa Young Lee, So-Young Park, Mi-Yeong Kim, Ji-Ho Lee, Byung-Keun Kim, Han-Ki Park, Min-Hye Kim, Sae-Hoon Kim, Sang-Heon Kim, Yoon-Seok Chang, Sang-Hoon Kim, Byung-Jae Lee, Kian Fan Chung, Sang-Heon Cho, Woo-Jung Song","doi":"10.1007/s00408-024-00674-6","DOIUrl":"10.1007/s00408-024-00674-6","url":null,"abstract":"<p><strong>Purpose: </strong>Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice.</p><p><strong>Methods: </strong>Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment.</p><p><strong>Results: </strong>Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn.</p><p><strong>Conclusions: </strong>Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"97-106"},"PeriodicalIF":4.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Osteopontin Predicts Clinical and Radiological Response in First-Line Treatment of Advanced Non-Small Cell Lung Cancer.","authors":"Davide Ramoni, Simona Coco, Giovanni Rossi, Chiara Dellepiane, Elisa Bennicelli, Sara Santamaria, Linda Zinoli, Alberto Stefano Tagliafico, Marco Tagliamento, Giulia Barletta, Luca Liberale, Amedeo Tirandi, Silvia Minetti, Maria Bertolotto, Fabrizio Montecucco, Carlo Genova, Federico Carbone","doi":"10.1007/s00408-024-00675-5","DOIUrl":"10.1007/s00408-024-00675-5","url":null,"abstract":"<p><strong>Purpose: </strong>Pembrolizumab-based regimens are conditioned by the expression of PD-L1, but durable response rate is limited by innate and acquired resistance mechanisms. Here, we focus on osteopontin (OPN), an upfront biomarker of senescence, which closely associated with natural history of non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>Seventy-nine patients eligible to pembrolizumab regimens-alone or in combination with chemotherapy-as first-line treatment of advanced NSCLC were enrolled. Predictive value of OPN toward iRECIST progression disease (PD) was set as first outcome. Secondary ones included performance status (ECOG) at baseline, early (first and best) responses, and overall survival (OS).</p><p><strong>Results: </strong>High Serum OPN characterized patients with worse ECOG-PS (p = 0.015) at baseline and subjects experienced PD/death at first (OR 1.17 [1.02 to 1.35]; p = 0.030) and best responses (0.04 [0.00 to 0.81]; p = 0.035). OPN was associated with time-to-progression (B -2.74 [-4.46 to -1.01]) and time-to death (-0.13 [-0.20 to -0.05]). Cox regression models unveil a predictive value for iRECIST-PD (HR 1.01 [1.00 to 1.02]; p = -0.005), RECIST-PD (HR 1.01 [1.00 to 1.02]; p = 0.017), and OS (HR 1.02 [1.01 to 1.03]; p = 0.001). These models were internally validated through bootstrap resampling and characterized by relevant discrimination ability at ROC curve analyses.</p><p><strong>Conclusion: </strong>Baseline levels of serum OPN is closely associated with performance status and short/long term outcomes in patients with advanced NSCLC, which are candidate to pembrolizumab-based regimens. As upfront biomarker of senescence, OPN may pave the way for future studies focusing on senescence patterns in NSCLC.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"197-210"},"PeriodicalIF":4.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11009777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119939","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}