ORCID Profile
0000-0002-2285-9970
Current Organisations
IRCCS FONDAZIONE Cà GRANDA OSPEDALE MAGGIORE POLICLINICO
,
Università degli Studi di Milano
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Publisher: European Respiratory Society (ERS)
Date: 31-01-2019
DOI: 10.1183/13993003.01183-2018
Abstract: 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 FEV
Publisher: Cold Spring Harbor Laboratory
Date: 23-07-2021
DOI: 10.1101/2021.07.21.21260624
Abstract: Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ∼0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5 th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA , a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.PUPT.2017.10.011
Abstract: Long acting muscarinic antagonists (LAMA) are currently considered the therapeutic mainstay for patients with COPD and have been shown to improve clinical outcomes including symptoms, exercise capacity and airflow limitation. Irisin, is a newly discovered hormone-like myokine generated by skeletal muscle cells in response to exercise and it is suggested to regulate energy expenditure and exercise capacity. The aim of the present study was to investigate if treatment with LAMA alters serum irisin levels in patients with COPD. Irisin was assessed by ELISA in the serum of 506 patients with COPD, GOLD II-IV, with a smoking history >10 PY, who were included in the PROMISE-COPD cohort. The effect of inhaled LAMA on serum irisin levels was evaluated in a proof-of-concept cohort of 40 COPD patients. Univariate linear regression analysis revealed that there was a significant negative association of irisin with age-adjusted Charlson score (p = 0.003) and a positive association of irisin with 6-min walking distance (6MWD) (p = 0.018) and treatment with LAMA (p = 0.004) but not with LABA or ICS. Multivariate analysis revealed that the association of irisin with LAMA treatment remains significant after adjustment for age-adjusted score and 6MWD. In the proof-of-concept cohort a single inhalation of LAMA stimulated serum irisin levels after 4 h. These findings imply that treatment of COPD patients with LAMA increase circulating irisin, thus explaining some of the beneficial extra-pulmonary effects of these drugs when used in the treatment of COPD.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Wiley
Date: 21-05-2017
DOI: 10.1111/ALL.13162
Abstract: Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for in iduals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment.
Publisher: Wiley
Date: 11-03-2019
Publisher: Springer Science and Business Media LLC
Date: 05-11-2022
DOI: 10.1038/S41598-022-23282-X
Abstract: The gut is of importance in the pathology of COVID-19 both as a route of infection, and gut dysfunction influencing the severity of disease. Systemic changes caused by SARS-CoV-2 gut infection include alterations in circulating levels of metabolites, nutrients and microbial products which alter immune and inflammatory responses. Circulating plasma markers for gut inflammation and damage such as zonulin, lipopolysaccharide and β-glycan increase in plasma along with severity of disease. However, Intestinal Fatty Acid Binding Protein / Fatty Acid Binding Protein 2 (I-FABP/FABP2), a widely used biomarker for gut cell death, has paradoxically been shown to be reduced in moderate to severe COVID-19. We also found this pattern in a pilot cohort of mild ( n = 18) and moderately severe ( n = 19) COVID-19 patients in Milan from March to June 2020. These patients were part of the first phase of COVID-19 in Europe and were therefore all unvaccinated. After exclusion of outliers, patients with more severe vs milder disease showed reduced FABP2 levels (median [IQR]) (124 [368] vs. 274 [558] pg/mL, P 0.01). A reduction in NMR measured plasma relative lipid-CH3 levels approached significance (median [IQR]) (0.081 [0.011] vs. 0.073 [0.024], P = 0.06). Changes in circulating lipid levels are another feature commonly observed in severe COVID-19 and a weak positive correlation was observed in the more severe group between reduced FABP2 and reduced relative lipid-CH3 and lipid-CH2 levels. FABP2 is a key regulator of enterocyte lipid import, a process which is inhibited by gut SARS-CoV-2 infection. We propose that the reduced circulating FABP2 in moderate to severe COVID-19 is a marker of infected enterocyte functional change rather than gut damage, which could also contribute to the development of hypolipidemia in patients with more severe disease.
Publisher: Wiley
Date: 22-03-2020
DOI: 10.1111/ALL.14204
Abstract: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK‐air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom‐medication scores obtained concurrently. All consecutive MASK‐air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users 205 904 days). Geolocalized users self‐assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom‐medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra‐in idual response variability (IRV) index was calculated. A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom‐medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.
Publisher: Springer Science and Business Media LLC
Date: 08-07-2021
DOI: 10.1038/S41586-021-03767-X
Abstract: The genetic make-up of an in idual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Publisher: European Respiratory Society (ERS)
Date: 04-2016
Publisher: Wiley
Date: 25-10-2018
Publisher: European Respiratory Society (ERS)
Date: 02-2000
DOI: 10.1034/J.1399-3003.2000.15B06.X
Abstract: There is evidence that infection with Chlamydia pneumoniae is associated with asthma of recent onset and that it can influence the severity of asthma. This has led to the suggestion that macrolide antibiotics may be useful in the treatment of asthma in subjects infected with C. pneumoniae. This study examined the association between immunoglobulin (Ig)G and IgA titres to C. pneumoniae and the severity of asthma. IgG and IgA antibodies to C. pneumoniae were measured in 619 subjects with asthma (18-60 yrs), using the microimmunofluoresence method. Subjects were asked about their use of asthma medicines, symptoms, previous hospitalization for asthma, smoking status and age of onset of asthma. In subjects with IgG titres of > or =1:64 and/or IgA titres > or =1:16 (n=212), spirometry was performed and peak expiratory flow rate (PEFR) and symptoms were recorded twice daily for 4 weeks on a diary card. The use of high dose inhaled steroids was associated with an increase of 74.1% in the titre of IgG antibodies (p=0.04) and an increase of 70.6% in the titre of IgA antibodies (p=0.0001) when compared with the use of low dose inhaled steroids. There was an inverse association between IgG antibodies and forced expiratory volume in one second (FEV1) as a percentage of predicted in those subjects with elevated IgG and/or IgA (p=0.04). In this group IgA antibodies were also associated with a higher daytime symptom score (p=0.04). Higher titres of antibodies to Chlamydia pneumoniae appears to be associated with markers of asthma severity. This raises the possibility that chronic infection with Chlamydia pneumoniae leads to an increase in the severity of asthma. Studies aimed at eradicating chronic infection with Chlamydia pneumoniae are necessary to determine whether or not this is the case.
Publisher: Springer Science and Business Media LLC
Date: 04-2021
DOI: 10.1038/S41591-021-01289-7
Abstract: Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced ersity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than in idual microbes, providing a fresh approach to the understanding of respiratory infection.
Publisher: European Respiratory Society (ERS)
Date: 31-08-2017
Abstract: In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areas To understand some of the key features of successful disease registries To review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 years To understand the key research priorities identified by EMBARC for the next 5 years
Publisher: European Respiratory Society (ERS)
Date: 06-2017
DOI: 10.1183/13993003.00051-2017
Abstract: There is a need for a clear definition of exacerbations used in clinical trials in patients with bronchiectasis. An expert conference was convened to develop a consensus definition of an exacerbation for use in clinical research. A systematic review of exacerbation definitions used in clinical trials from January 2000 until December 2015 and involving adults with bronchiectasis was conducted. A Delphi process followed by a round-table meeting involving bronchiectasis experts was organised to reach a consensus definition. These experts came from Europe (representing the European Multicentre Bronchiectasis Research Collaboration), North America (representing the US Bronchiectasis Research Registry/COPD Foundation), Australasia and South Africa. The definition was unanimously approved by the working group as: a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough sputum volume and/or consistency sputum purulence breathlessness and/or exercise tolerance fatigue and/or malaise haemoptysis AND a clinician determines that a change in bronchiectasis treatment is required. The working group proposes the use of this consensus-based definition for bronchiectasis exacerbation in future clinical research involving adults with bronchiectasis.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.BJA.2018.07.039
Abstract: Recruitment manoeuvres generate a transient increase in trans-pulmonary pressure that could open collapsed alveoli. Recruitment manoeuvres might generate very high inspiratory airflows. We evaluated whether recruitment manoeuvres could displace respiratory secretions towards the distal airways and impair gas exchange in a porcine model of bacterial pneumonia. We conducted a prospective randomised study in 10 mechanically ventilated pigs. Pneumonia was produced by direct intra-bronchial introduction of Pseudomonas aeruginosa. Four recruitment manoeuvres were applied randomly: extended sigh (ES), maximal recruitment strategy (MRS), sudden increase in driving pressure and PEEP (SI-PEEP), and sustained inflation (SI). Mucus transport was assessed by fluoroscopic tracking of radiopaque disks before and during each recruitment manoeuvre. The effects of each RM on gas exchange were assessed 15 min after the intervention. Before recruitment manoeuvres, mucus always cleared towards the glottis. Conversely, mucus was displaced towards the distal airways in 28.6% ES applications and 50% of all other recruitment manoeuvres (P=0.053). Median mucus velocity was 1.26 mm min Recruitment manoeuvres dislodge mucus distally, irrespective of airflow generated by different recruitment manoeuvres. Further investigation in humans is warranted to corroborate these pre clinical findings, as there may be limited benefits associated with lung recruitment in pneumonia.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2018
Publisher: European Respiratory Society (ERS)
Date: 2016
DOI: 10.1183/23120541.00081-2015
Abstract: 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 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.
Publisher: Wiley
Date: 29-07-2016
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.CHEST.2016.08.1440
Abstract: Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD. In a prospective, observational, multicenter study including 506 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease grades II to IV), serum s les were analyzed at stable state, exacerbation, and 4 weeks after exacerbation. The analysis comprised a panel of five novel neoepitopes, including fragments of collagen type III (C3M) and collagen type VI (C6M), pro-forms of collagen type III (Pro-C3) and type VI (Pro-C6), and neutrophil elastase-generated fragments of elastin (EL-NE) according to enzyme-linked immunosorbent assay. These neoepitopes were also measured at stable state in a derivation cohort that included 100 patients with COPD. Serum levels of C3M, C6M, Pro-C3, Pro-C6, and EL-NE were associated with lung function. Patients with the lowest levels of Pro-C3 and Pro-C6 had more severe airflow limitation, hyperinflation, air trapping, and emphysema. C3M and C6M were associated with dyspnea. All ECM biomarkers, except Pro-C6, were increased at exacerbation compared with stable state but, except EL-NE, did not differ between stable state and exacerbation follow-up in the crude and adjusted analyses. In Cox regression adjusted analyses, Pro-C3 was associated with a shorter time to exacerbation (hazard ratio, 0.72 CI, 0.59-0.89 P = .002) and Pro-C6 with survival (hazard ratio, 2.09 CI, 1.18-3.71 P = .011). Serum biomarkers of ECM turnover were significantly associated with disease severity and clinically relevant outcomes in patients with COPD. No.: ISRCTN99586989 URL: www.controlled-trials.com.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.JACI.2018.08.049
Abstract: Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
Publisher: Wiley
Date: 20-02-2017
Publisher: Wiley
Date: 12-2016
Publisher: European Respiratory Society (ERS)
Date: 12-06-2014
DOI: 10.1183/09031936.00014614
Abstract: The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure 3) aiding risk stratification in chronic disease patients, using a common strategy 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing) 5) proposing a common simulation tool to assist physicians and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).
Publisher: Springer Science and Business Media LLC
Date: 23-11-2016
Location: Italy
No related grants have been discovered for Francesco Blasi.