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Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of global mortality. Despite clinical predictors (age, severity, comorbidities, etc.) being established, proteomics offers comprehensive biological profiling to obtain deeper insights into COPD pathophysiology and survival prognoses. This pilot study aimed to identify proteomic footprints that could be potentially useful in predicting mortality in stable COPD patients. Plasma samples from 40 patients were subjected to both blind (liquid chromatography–mass spectrometry) and hypothesis-driven (multiplex immunoassays) proteomic analyses supported by artificial intelligence (AI) before a 4-year clinical follow-up. Among the 34 patients whose survival status was confirmed (mean age 69 ± 9 years, 29.5% women, FEV1 42 ± 15.3% ref.), 32% were dead in the fourth year. The analysis identified 363 proteins/peptides, with 31 showing significant differences between the survivors and non-survivors. These proteins predominantly belonged to different aspects of the immune response (12 proteins), hemostasis (9), and proinflammatory cytokines (5). The predictive modeling achieved excellent accuracy for mortality (90%) but a weaker performance for days of survival (Q2 0.18), improving mildly with AI-mediated blind selection of proteins (accuracy of 95%, Q2 of 0.52). Further stratification by protein groups highlighted the predictive value for mortality of either hemostasis or pro-inflammatory markers alone (accuracies of 95 and 89%, respectively). Therefore, stable COPD patients' proteomic footprints can effectively forecast 4-year mortality, emphasizing the role of inflammatory, immune, and cardiovascular events. Future applications may enhance the prognostic precision and guide preventive interventions. [ABSTRACT FROM AUTHOR]

Background: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. Method: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. Results: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. Conclusions: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. Trial registration: www.clinicaltrials.gov (ID: NCT04180319). [ABSTRACT FROM AUTHOR]

Objectives Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies. Methods We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants. Results We observed statistically significant increased levels of sP-selectin (P =.015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%). Conclusions The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies. [ABSTRACT FROM AUTHOR]

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design., Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement., Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event., Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD., Competing Interests: Conflict of interest: K. Waeijen-Smit, M. Crutsen, S. Keene, T.J. Ringbæk, F. Fabbian, C-t. Lun, B. Ergan, C. Estebam, J.M. Quintana Lopez, C.L. Chang, R.J. Hancox, E. Shafuddin, H. Ellis, C. Janson, G. Gudmundsson, D. Epstein, A. Lacoma, C. Osadnik, I. Alia, F. Spannella, Z. Karakurt, H. Mehravaran, C. Utens, M.D. de Kruif, F.W.S. Ko, S.P. Trethewey, K. Vermeersch, S. Zilberman-Itskovich, C. Echevarria, R.T.M. Sprooten, P. Faverio, H.J. Prins and S. Houben-Wilke have no grants or personal fees to report. Conflict of interest: M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi and Grifols and research grants from Grifols. Conflict of interest: E. Crisafulli has received honoraria for lecturing, scientific advisory boards and participation in clinical studies for AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis, Qbgroup and Sanofi. Conflict of interest: A. Torres reports speaker/consulting honoraria from Pfizer, MSD, Janssen and Biomerieux. Conflict of interest: C. Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the University of Basel, the University Hospital Basel, the KTI, Abbott, Beckman Coulter, BRAHMS, Idorsia, LSI-Medience, Ortho Diagnostics, Novartis, Roche, Siemens, SpinChip and Singulex, as well as speaker/consulting honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Idorsia, Novartis, Osler, Roche, SpinChip and Sanofi, all outside the submitted work. Conflict of interest: P. Schuetz has received grants from Nestle, Abbot, bioMerieux and Thermofisher outside the submitted work. Conflict of interest: E. Mekov has received grants and personal fees from Chiesi, and speaker or consulting fees from AstraZeneca and Chiesi. Conflict of interest: T.H. Harries is supported by a National Institute for Health and Care Research Academic Clinical Lectureship. Conflict of interest: J.L. López-Campos has received honoraria during the last 3 years for lecturing, scientific advice, participation in clinical studies or writing for publications for (alphabetical order): AstraZeneca, Bial, Boehringer, Chiesi, CSL Behring, Faes, Ferrer, Gebro, Grifols, GSK, Megalabs, Menarini and Novartis. Conflict of interest: C.S. Ulrik has received personal fees and grants from AstraZeneca, Chiesi, Boehringer Ingelheim, GSK, Novartis, Sanofi, Menarini, TEVA, ALK-Abello, Takeda, Orion Pharma, TFF Pharmaceuticals and Covis Pharma outside the submitted work. Conflict of interest: J. Dominguez has received honoraria for lectures from Oxford Immunotec (UK) and received payments for license transference from GenID (Germany), and grants from La Fundació La Marató TV3, Instituto de Salud Carlos III (CP03/00112), Catalan Pulmonology Society (SOCAP), Catalan Pulmonology Foundation (FUCAP) and Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). Conflict of interest: A.M. Turner reports research grants outside the submitted work from AstraZeneca, Resmed, Phillips, Chiesi, Grifols, CSL Behring and NIHR, and honoraria from GSK and Boehringer Ingelheim. Conflict of interest: D. Bumbacea has received grants and personal fees in the last 3 years from AstraZeneca, Eli Lilly, Novartis, Sanofi and Synairgen outside of the submitted work. Conflict of interest: PBM has received grants and personal fees from Philips, ResMed, Breas, Chiesi, Fischer & Paykel and, Sanofi outside the submitted work. Conflict of interest: J. Steer has received grants and honoraria, outside the submitted work, from Chiesi, Menarini Group, AstraZeneca and Pfizer. Conflict of interest: S.C. Bourke has received research grants from GSK (BEC COPD IRAS 285200), and additional support from Radiometer for an NIHR-funded study (NIVOW IRAS 313485), Philips, ResMed, and Pfizer Open Air, took part in clinical advisory boards with Philips and AstraZeneca, and has received honoraria from Boehringer Ingelheim, Chiesi, GSK, and AstraZeneca. Conflict of interest: N. Lane reports research grants from Bright Northumbria and The ResMed Foundation; and nonfinancial support from Chiesi and BREAS outside the submitted work. Conflict of interest: J. de Batlle acknowledges receiving financial support from Instituto de Salud Carlos III (Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund, “Investing in your future”. Conflict of interest: R. Russell has received personal fees, outside of the submitted work, from AstraZeneca, Chiesi, Covis, GlaxoSmithKline and Boehringer Ingelheim. Conflict of interest: J.L. Cross has received grants from National Institute of Health Research. Conflict of interest: M.A. Spruit has received grants from the Netherlands Lung Foundation, Stichting Asthma Bestrijding, AstraZeneca, Boehringer Ingeheim, TEVA and CHIESI outside the submitted work. Conflict of interest: S.O. Simons has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Chiesi outside the submitted work. Conflict of interest: F.M.E. Franssen has received grants and personal fees from AstraZeneca, Chiesi, Boehringer Ingelheim, Glaxosmithkline, Novartis and MSD outside the submitted work. Conflict of interest: All authors declare no conflicts of interest in relation to the present study., (Copyright ©The authors 2024.)