Browsing by Author "Blasi, Francesco (57211284402)"

Background Current multicomponent scores that predict mortality in COPD patients might underestimate the systemic component of COPD. Therefore, we evaluated the accuracy of circulating levels of proadrenomedullin (MR-proADM) alone or combined with the ADO (Age, Dyspnoea, airflow Obstruction), updated ADO or BOD (Body mass index, airflow Obstruction, Dyspnoea) index to predict all-cause mortality in stable COPD patients. Methods This study pooled data of 1285 patients from the COMIC and PROMISE-COPD study. Results Patients with high MR-proADM levels (≥0.87 nmol/l) had a 2.1 fold higher risk of dying than those with lower levels (p < 0.001). Based on the C-statistic, the ADOA index (ADO plus MR-proADM) (C = 0.72) was the most accurate predictor followed by the BODA (BOD plus MR-proADM) (C = 0.71) and the updated ADOA index (updated ADO plus MR-proADM) (C = 0.70). Adding MR-proADM to ADO and BOD was superior in forecasting 1- and 2-year mortality. The net percentages of persons with events correctly reclassified (NRI+) within respectively 1-year and 2-year was 31% and 20% for ADO, 31% and 20% for updated ADO and 25% and 19% for BOD. The net percentages of persons without events correctly reclassified (NRI-) within respectively 1-year and 2-year was 26% and 27% for ADO, 27% and 28% for updated ADO and 34% and 34% for BOD. Conclusions Adding MR-proADM increased the predictive power of BOD, ADO and updated ADO index. © 2015 Elsevier Ltd.

The BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index is wellvalidated for mortality prediction in chronic obstructive pulmonary disease (COPD). Concentrations of plasma pro-adrenomedullin, a surrogate for mature adrenomedullin, independently predicted 2-year mortality among inpatients with COPD exacerbation. We compared accuracy of initial pro-adrenomedullin level, BODE and BODE components, alone or combined, in predicting 1-year or 2-year all-cause mortality in a multicentre, multinational observational cohort with stable, moderate to very severe COPD. Pro-adrenomedullin was significantly associated (p<0.001) with 1-year mortality (4.7%) and 2-year mortality (7.8%) and comparably predictive to BODE regarding both (C statistics 0.691 versus 0.745 and 0.635 versus 0.679, respectively). Relative to using BODE alone, adding pro-adrenomedullin significantly improved 1-year and 2-year mortality prognostication (C statistics 0.750 and 0.818, respectively; both p<0.001). Pro-adrenomedullin plus BOD was more predictive than the original BODE including 6-min walk distance. In multivariable analysis, pro-adrenomedullin (likelihood ratio Chi-squared 13.0, p<0.001), body mass index (8.5, p50.004) and 6-min walk distance (7.5, p50.006) independently foretold 2-year survival, but modified Medical Research Council dyspnoea score (2.2, p50.14) and forced expiratory volume in 1 s % predicted (0.3, p50.60) did not. Pro-adrenomedullin plus BODE better predicts mortality in COPD patients than does BODE alone; proadrenomedullin may substitute for 6-min walk distance in BODE when 6-min walk testing is unavailable. Copyright © ERS 2014.

Background: Who should be tested for viruses in patients with community acquired pneumonia (CAP), prevalence and risk factors for viral CAP are still debated. We evaluated the frequency of viral testing, virus prevalence, risk factors and treatment coverage with oseltamivir in patients admitted for CAP. Methods: Secondary analysis of GLIMP, an international, multicenter, point-prevalence study of hospitalized adults with CAP. Testing frequency, prevalence of viral CAP and treatment with oseltamivir were assessed among patients who underwent a viral swab. Univariate and multivariate analysis was used to evaluate risk factors. Results: 553 (14.9%) patients with CAP underwent nasal swab. Viral CAP was diagnosed in 157 (28.4%) patients. Influenza virus was isolated in 80.9% of cases. Testing frequency and viral CAP prevalence were inhomogeneous across the participating centers. Obesity (OR 1.59, 95%CI: 1.01–2.48; p = 0.043) and need for invasive mechanical ventilation (OR 1.62, 95%CI: 1.02–2.56; p = 0.040) were independently associated with viral CAP. Prevalence of empirical treatment with oseltamivir was 5.1%. Conclusion: In an international scenario, testing frequency for viruses in CAP is very low. The most common cause of viral CAP is Influenza virus. Obesity and need for invasive ventilation represent independent risk factors for viral CAP. Adherence to recommendations for treatment with oseltamivir is poor. © 2018 European Federation of Internal Medicine

BACKGROUND:The prevalence of exertional hypoxemia in unselected patients with COPD is unknown. Intermittent hypoxia leads to adrenomedullin (ADM) upregulation through the hypoxia-inducible factor-1 pathway. We aimed to assess the prevalence and the annual probability to develop exertional hypoxemia in stable COPD. We also hypothesized that increased ADM might be associated with exertional hypoxemia and envisioned that adding ADM to clinical variables might improve its prediction in COPD. METHODS:A total of 1,233 6-min walk tests and circulating proadrenomedullin (proADM) levels from 574 patients with clinically stable, moderate to very severe COPD enrolled in a multinational cohort study and followed up for 2 years were concomitantly analyzed. RESULTS:The prevalence of exertional hypoxemia was 29.1%. In a matrix derived from a fitted-multistate model, the annual probability to develop exertional hypoxemia was 21.6%. Exertional hypoxemia was associated with greater deterioration of specific domains of health-related quality of life, higher severe exacerbation, and death annual rates. In the logistic linear and conditional Cox regression multivariable analyses, both FEV 1% predicted and proADM proved independent predictors of exertional hypoxemia ( P<.001 for both). Adjustment for comorbidities, including cardiovascular disorders, and exacerbation rate did not influence results. Relative to using FEV 1% predicted alone, adding proADM resulted in a significant improvement of the predictive properties ( P = .018). Based on the suggested nonlinear nomogram, patients with moderate COPD (FEV 1% predicted 5 50%) but high proADM levels (>2 nmol/L) presented increased risk (>30%) for exertional desaturation. CONCLUSIONS:Exertional desaturation is common and associated with poorer clinical outcomes in COPD. ADM improves prediction of exertional desaturation as compared with the use of FEV 1% predicted alone. TRIAL REGISTRY:ISRCTN Register; No.:ISRCTN99586989; URL:www.controlled-trials.com © 2014 American College of Chest Physicians.

Background: Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease. We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbations of COPD PROMISE-COPD cohort. Methods: We followed 277 patients with stable COPD GOLD stage II-IV COPD over a median period of 733 days (IQR 641-767) taking survival as the primary outcome parameter. Patients were dichotomized as frequent (≥2 AECOPD/year) or infrequent exacerbators. Serum MBL levels and single nucleotide polymorphisms of the MBL2 gene were assessed at baseline. Results: The MBL2-HYPD haplotype was significantly more prevalent in frequent exacerbators (OR: 3.33; 95 % CI, 1.24-7.14, p=0.01). The median serum MBL concentration was similar in frequent (607 ng/ml, [IQR; 363.0-896.0 ng/ml]) and infrequent exacerbators (615 ng/ml, [IQR; 371.0-942.0 ng/ml]). Serum MBL was not associated with lung function characteristics or bacterial colonization in sputum. However, high serum MBL at stable state was associated with better survival compared to low MBL (p=0.046, log rank test). Conclusions: In COPD, the HYPD haplotype of MBL2 gene is associated with frequent exacerbations and high serum MBL is linked to increased survival. The PROMISE-COPD study was registered at www.controlled-trials.comunder the identifier ISRCTN99586989. © 2015 Mandal et al.

Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD). However, choice of parameters and score complexity restrict clinical applicability. Our aim was to provide and validate a simplified COPD risk index independent of lung function. The PROMISE study (n=530) was used to develop a novel prognostic index. Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality. External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988). Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C. It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05). Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively). External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05). The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk. Copyright © ERS 2016.

Hyaluronic acid (HA) and its degradation products play an important role in lung pathophysiology and airway remodelling in chronic obstructive pulmonary disease (COPD). We investigated if HA and its degrading enzyme hyaluronidase (HYAL)-1 are associated with COPD severity and outcome. Serum HA was assessed in a discovery cohort of 80 COPD patients at stable state and exacerbations. HA, HYAL-1 and HYAL-1 enzymatic activity were evaluated at stable state, exacerbations and 4 weeks after exacerbations in 638 COPD patients from the PROMISE validation cohort. In the discovery cohort, serum HA was higher at exacerbations compared with the stable state (p=0.015). In the validation cohort, HA was higher at moderate and severe exacerbations than at baseline (p<0.001), and remained higher after 4 weeks (p<0.001). HA was strongly predictive for overall survival since it was associated with time to death (p<0.001) independently of adjusted Charlson score, annual exacerbation rate and BODE (body mass, airflow obstruction, dyspnoea, exercise capacity) index. Serum HYAL-1 was increased at moderate (p=0.004) and severe (p=0.003) exacerbations, but decreased after 4 weeks (p<0.001). HYAL-1 enzymatic activity at stable state was inversely correlated with FEV1 % pred (p=0.034) and survival time (p=0.017). Serum HA is associated with COPD severity and predicts overall survival. Degradation of HA is associated with airflow limitation and impairment of lung function. Copyright ©ERS 2019

Bronchiectasis is one of the most neglected diseases in respiratory medicine. There are no approved therapies and few large-scale, representative epidemiological studies. The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) registry is a prospective, pan-European observational study of patients with bronchiectasis. The inclusion criterion is a primary clinical diagnosis of bronchiectasis consisting of: 1) a clinical history consistent with bronchiectasis; and 2) computed tomography demonstrating bronchiectasis. Core exclusion criteria are: 1) bronchiectasis due to known cystic fibrosis; 2) age <18 years; and 3) patients who are unable or unwilling to provide informed consent. The study aims to enrol 1000 patients by April 2016 across at least 20 European countries, and 10 000 patients by March 2020. Patients will undergo a comprehensive baseline assessment and will be followed up annually for up to 5 years with the goal of providing high-quality longitudinal data on outcomes, treatment patterns and quality of life. Data from the registry will be available in the form of annual reports. and will be disseminated in conference presentations and peer-reviewed publications. The European Bronchiectasis Registry aims to make a major contribution to understanding the natural history of the disease, as well as guiding evidence-based decision making and facilitating large randomised controlled trials. © ERS 2015.