silvestro d'anna
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Scopus Publications
- The Muco-Microbiotic Layer in Respiratory Pathophysiology: Integrating Transcriptomics, Inflammation Phenotypes, and Clinical Biomarkers in Precision Pulmonology
Claudio Candia, Adelaide Carista, Melania Ionelia Gratie, Domiziana Picone, Giuseppa D’Amico, Celeste Caruso Bavisotto, Fabio Bucchieri, Silvestro Ennio D’Anna, Alessandro Pitruzzella, Mauro Maniscalco, Giuseppe Bonaventura, Stefano Burgio, Francesco Cappello
Biology, 2026
The lower airways are a dynamic environment where physical, microbial, and molecular factors intersect to regulate respiratory health and disease. The muco-microbiotic (MuMi) layer, composed of mucus, resident microbes, and extracellular vesicles (EVs), is not just a passive barrier but also an active site for host–microbe communication. This layer integrates epithelial cell biology, microbial activity, and immune responses within the bronchial environment. New transcriptomic and metatranscriptomic technologies show that it is not only which microbes are present but also their gene activity that closely links to airway inflammation and disease. EV-associated RNAs from both host and microbial cells act as key messengers, influencing epithelial responses, immune activity, mucus properties, and microbial behaviour. This review highlights evidence that positions the MuMi layer as central to understanding lower airway disease, particularly asthma and chronic obstructive pulmonary disease (COPD). Distinct gene expression programs and biomarker profiles, such as exhaled nitric oxide, may reflect different disease mechanisms even in cases with similar clinical features, such as eosinophilia. Multi-omic approaches focused on the MuMi layer enable better disease classification, biomarker discovery, and therapy selection. By putting the MuMi interface at the core of precision pulmonology, we provide a framework for advancing personalised care in chronic respiratory diseases. - A case scenario study on adherence to GINA recommendations by primary care physicians in an area of Southern Italy: the “Progetto Padre 2.0”
Mauro Maniscalco, Claudio Candia, Marta Coppola, Silvestro Ennio D’Anna, Carmen Lombardi, Claudia Merola, Antonio Iovine, Pasquale Ambrosino, Antonio Molino, Salvatore Fuschillo
BMC Primary Care, 2025
BACKGROUND: Accurate diagnosis and management of bronchial asthma are complex processes guided by national and international asthma guidelines, particularly the Global Initiative for Asthma (GINA). However, adherence to these guidelines is often suboptimal, varying across healthcare professionals and countries, which can lead to poor asthma control and increased healthcare costs. AIM: In this observational study, we assessed the alignment to GINA recommendations in the diagnosis and management of asthma among 15 primary care physicians in two metropolitan areas of the Campania region, Southern Italy. METHODS: 120 patients were randomly selected from the electronic medical records of 15 primary care physicians. Afterwards, the alignment of diagnostic pathways and treatments with current GINA recommendations was assessed by an experienced chest physician. Three main outcomes were defined: diagnostic congruence, diagnostic workup congruence, and therapeutic congruence. RESULTS: Overall, 26.7% of our sample presented with an incongruous asthma diagnosis, while only 46.7% patients had therapeutic prescriptions in line with the latest GINA document recommendations. Patients treated in accordance with GINA recommendations exhibited significantly higher ACT scores, averaging 20.5 ± 4.0, compared to those receiving non-guideline-directed therapy, who averaged 15.7 ± 6.1 (p < 0.001). Diagnostic congruence showed a direct correlation with atopy (r = 0.277, p = 0.002) and an inverse correlation with ACT score (r = -0.335, p < 0.001). CONCLUSIONS: The results of this study indicate that adherence to asthma guidelines in the metropolitan areas of Naples and Benevento remains insufficient. Further research focused on developing individualized interventions to manage non-adherence is warranted. - Appearances can be deceiving: differences in FeNO values among COPD and severe asthmatic patients stratified according to peripheral eosinophilic count
Claudio Candia, Silvestro Ennio D'Anna, Maria D'Amato, Francesco Cappello, Andrea Motta, Mauro Maniscalco
Nitric Oxide Biology and Chemistry, 2025 - Impaired SERPIN–Protease Balance in the Peripheral Lungs of Stable COPD Patients
Antonino Di Stefano, Francesco Nucera, Umberto Rosani, Paola Brun, Isabella Gnemmi, Mauro Maniscalco, Silvestro Ennio D’Anna, Andrea Leonardi, Vitina Carriero, Francesca Bertolini, Josè Freni, Antonio Ieni, Sebastiano Gangemi, Paolo Ruggeri, Fabio Luigi Massimo Ricciardolo
International Journal of Molecular Sciences, 2025
The protease–antiprotease balance is involved in many biological processes, including blood coagulation, tissue remodeling, inflammation and immune responses. The aim of this study is to determine the balance between SERPINs and some related proteases in the lungs of stable COPD patients. In this cross-sectional study, the expression and localization of human SERPINs (anti-proteases) and some related proteases were measured in the lung parenchyma of mild-moderate COPD (MCOPD, n = 13) patients, control smokers (CS, n = 14) and control nonsmokers (CNS, n = 12) using transcriptome analysis, immunohistochemistry, and ELISA tests. Peripheral lung transcriptomic data showed increased mRNA levels of tissue plasminogen activator (tPA), cathepsin-L and caspase-1 as well as increased SERPINs A6, B3, B5, B11, B13 in the COPD group compared to the CNS group. At the protein level, IHC analysis showed that tPA and cathepsin-L increased in the bronchiolar epithelium and alveolar septa of the CS and COPD groups compared to the CNS group, as well as SERPINB5 and B13 in the alveolar macrophages and alveolar septa of the CS and COPD groups compared to the CNS group. SERPINA6 was shown to be decreased in the bronchiolar epithelium, bronchiolar lamina propria, and alveolar septa of the CS and COPD groups compared to the CNS group and was positively correlated with lung function. SERPINB3 was decreased in the alveolar septa of the CS group compared to the CNS group. The ELISA tests showed that in the total lung extracts, decreased levels of SERPINA6 and increased caspase-1 were shown in the COPD group compared to the CNS or both control groups, respectively. These data show an imbalance, at the protein level, of SERPINs and some related proteases in the lungs of the CS and stable COPD groups. These alterations may play a role in damaging the lung parenchyma of susceptible COPD patients. - Long-term inhaled corticosteroid treatment in patients with chronic obstructive pulmonary disease, cardiovascular disease, and a recent hospitalised exacerbation: The ICSLIFE pragmatic, randomised controlled study
Alberto Papi, Giacomo Forini, Mauro Maniscalco, Elena Bargagli, Claudia Crimi, Pierachille Santus, Antonio Molino, Valeria Bandiera, Federico Baraldi, Silvestro Ennio D'Anna, Mauro Carone, Maurizio Marvisi, Corrado Pelaia, Giulia Scioscia, Vincenzo Patella, Maria Aliani, Leonardo M Fabbri, Giuseppina Schipani, Raffaele Antonello Incalzi, Paola Rogliani, Piero Ceriana, Antonio Spanevello, Bruno Balbi, Maria Pia Foschino, Nicola Scichilone, Ombretta Para, Carlo Nozzoli, Francesco Dentali, Bianca Beghè, Manlio Milanese, Eugenia Monaco, Angelo Guido Corsico, Nicola Facciolongo, Carlo Barbetta, Martina Bonifazi, Micaela Romagnoli, Corrado Pelaia, Fabiano di Marco, Andrea Bianco, Alberto Papi, Mauro Maniscalco, Elena Bargagli, Claudia Crimi, Pierachille Santus, Enea Tazzari, Luca Ronzoni, Federica Santoli, Antonio Molino, Maurizio Marvisi, Vincenzo Patella, Maria Aliani
European Journal of Internal Medicine, 2024 - Autoimmunity against Nucleus Ambiguous Is Putatively Possible in Both Long-COVID-19 and Vaccinated Subjects: Scientific Evidence and Working Hypothesis
Silvestro Ennio D’Anna, Alessandra Maria Vitale, Giuseppa D’Amico, Celeste Caruso Bavisotto, Pasquale Ambrosino, Francesco Cappello, Mauro Maniscalco, Antonella Marino Gammazza
Biology, 2024
As reported by the World Health Organization (WHO), about 10–20% of people have experienced mid- to long-term effects following SARS-CoV-2 infection, collectively referred to as post-COVID-19 condition or long-COVID, including some neurovegetative symptoms. Numerous findings have suggested that the onset of these neurovegetative symptoms upon viral infection may be caused by the production of autoantibodies through molecular mimicry phenomena. Accordingly, we had previously demonstrated that 22 of the human proteins sharing putatively immunogenic peptides with SARS-CoV-2 proteins are expressed in the dorsal motor nucleus and nucleus ambiguous. Therefore, if molecular mimicry occurs following severe forms of COVID-19, there could be transitory or permanent damage in some vagal structures, resulting in a lower vagal tone and all the related clinical signs. We investigated the presence of autoantibodies against two proteins of vagal nuclei sharing a peptide with SARS-CoV-2 spike glycoprotein using an immunoassay test on blood obtained from patients with cardiorespiratory symptoms in patients affected by ongoing symptomatic COVID-19 (long-COVID), subjects vaccinated without a history of SARS-CoV-2 infection, and subjects not vaccinated without a history of SARS-CoV-2 infection. Interestingly, putative autoantibodies were present in both long-COVID-19 and vaccinated groups, opening interesting questions about pathogenic mechanisms of the disease. - Upregulation of Notch Signaling and Cell-Differentiation Inhibitory Transcription Factors in Stable Chronic Obstructive Pulmonary Disease Patients
Antonino Di Stefano, Isabella Gnemmi, Umberto Rosani, Mauro Maniscalco, Silvestro Ennio D’Anna, Paola Brun, Vitina Carriero, Francesca Bertolini, Bruno Balbi, Fabio Luigi Massimo Ricciardolo
International Journal of Molecular Sciences, 2024
Notch signaling is involved in the prevention of cell differentiation and cell fate in various organs, including the lungs. We aimed to determine the transcriptomic and protein expression of Notch receptors, their ligands, and related transcription factors in stable COPD. The expression and localization of Notch receptors, their ligands, and related transcription factors were measured in bronchial biopsies of individuals with stable mild/moderate (MCOPD) (n = 18) or severe/very severe (SCOPD) (n = 16) COPD, control smokers (CSs) (n = 13), and control nonsmokers (CNSs) (n = 11), and in the lung parenchyma of those with MCOPD (n = 13), CSs (n = 10), and CNSs (n = 10) using immunohistochemistry, ELISA tests, and transcriptome analyses. In the bronchial biopsies, Notch4 and HES7 significantly increased in the lamina propria of those with SCOPD compared to those with MCOPD, CSs, and CNSs. In the peripheral lung bronchiolar epithelium, Notch1 significantly increased in those with MCOPD and CSs compared to CNSs. ELISA tests of lung parenchyma homogenates showed significantly increased Notch2 in those with MCOPD compared to CSs and CNSs. Transcriptomic data in lung parenchyma showed increased DLL4 and HES1 mRNA levels in those with MCOPD and CSs compared to CNSs. These data show the increased expression of the Notch pathway in the lungs of those with stable COPD. These alterations may play a role in impairing the regenerative–reparative responses of diseased bronchioles and lung parenchyma. - Exploring novel perspectives on eosinophilic inflammation in severe asthma
Claudio Candia, Pasquale Ambrosino, Silvestro E D’Anna, Andrea Motta, Mauro Maniscalco
Biomarkers in Medicine, 2024
Two recent articles by the same research group documented that patients with severe eosinophilic asthma exhibit an increased proportion of a subtype of eosinophils, namely CD62Llow inflammatory eosinophils (iEos) and identified an intriguing correlation between such iEos and asthma control scores. Moreover, CD62Llow iEos were reduced after treatment with the anti-IL-5 monoclonal antibody mepolizumab. In the future, we believe that eosinophil subtypes could represent a useful biomarker in severe eosinophilic asthma, helping clinicians characterize patient endotypes and monitoring the response to biological drugs. - The Role of High-Flow Nasal Cannula Oxygen Therapy in Exercise Testing and Pulmonary Rehabilitation: A Review of the Current Literature
Claudio Candia, Carmen Lombardi, Claudia Merola, Pasquale Ambrosino, Silvestro Ennio D’Anna, Aldo Vicario, Stefania De Marco, Antonio Molino, Mauro Maniscalco
Journal of Clinical Medicine, 2024
High-flow nasal cannula (HFNC) has recently emerged as a crucial therapeutic strategy for hypoxemic patients both in acute and chronic settings. Indeed, HFNC therapy is able to deliver higher fractions of inspired oxygen (FiO2) with a heated and humidified gas flow ranging from 20 up to 60 L per minute, in a more comfortable way for the patient in comparison with Conventional Oxygen Therapy (COT). In fact, the flow keeps the epithelium of the airways adequately moisturized, thus positively affecting the mucus clearance. Finally, the flow is able to wash out the carbon dioxide in the dead space of the airways; this is also enhanced by a modest positive end-expiratory pressure (PEEP) effect. Recent evidence has shown applications of HFNC in exercise training and chronic settings with promising results. In this narrative review, we explored how HFNC might contribute to enhancing outcomes of exercise training and pulmonary rehabilitation among patients dealing with chronic obstructive pulmonary disease, interstitial lung diseases, and lung cancer. - Pulmonary rehabilitation and endothelial function in patients with chronic obstructive pulmonary disease: A prospective cohort study
Pasquale Ambrosino, Matteo Nicola Dario Di Minno, Silvestro Ennio D'Anna, Roberto Formisano, Nicola Pappone, Costantino Mancusi, Antonio Molino, Andrea Motta, Mauro Maniscalco
European Journal of Internal Medicine, 2023 - Cardiovascular Risk Associated with Alpha-1 Antitrypsin Deficiency (AATD) Genotypes: A Meta-Analysis with Meta-Regressions
Pasquale Ambrosino, Giuseppina Marcuccio, Carmen Lombardi, Silvestro Ennio D’Anna, Stefano Sanduzzi Zamparelli, Costantino Mancusi, Giorgio Alfredo Spedicato, Andrea Motta, Mauro Maniscalco
Journal of Clinical Medicine, 2023 - Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients
Antonino Di Stefano, Umberto Rosani, Stefano Levra, Isabella Gnemmi, Paola Brun, Mauro Maniscalco, Silvestro Ennio D’Anna, Vitina Carriero, Francesca Bertolini, Fabio L. M. Ricciardolo
Biology, 2023 - Bacterial load and related innate immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease
Silvestro Ennio D'Anna, Francesca Dossena, Isabella Gnemmi, Paola Brun, Antonio Spanevello, Vitina Carriero, Francesca Bertolini, Mauro Maniscalco, Fabio LM. Ricciardolo, Bruno Balbi, Antonino Di Stefano
Respiratory Medicine, 2023 - Decreased humoral immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease
Antonino Di Stefano, Francesca Dossena, Isabella Gnemmi, Silvestro Ennio D’Anna, Paola Brun, Bruno Balbi, Alessio Piraino, Antonio Spanevello, Francesco Nucera, Vitina Carriero, Francesca Bertolini, Mauro Maniscalco, Ian M. Adcock, Gaetano Caramori, Fabio L. M. Ricciardolo
Respiratory Research, 2022 - Is It All about Endothelial Dysfunction? Focusing on the Alteration in Endothelial Integrity as a Key Determinant of Different Pathological Mechanisms
Pasquale Ambrosino, Silvestro Ennio D’Anna, Guido Grassi, Mauro Maniscalco
Biomedicines, 2022 - Bronchodilator Response as a Possible Predictor of Lung Function Improvement After Pulmonary Rehabilitation in Post-COVID-19 Patients
Mauro Maniscalco, Salvatore Fuschillo, Pasquale Ambrosino, Silvestro Ennio D’Anna, Maria Sofia Accardo, Maria Gabriella Matera, Mario Cazzola
Archivos De Bronconeumologia, 2022 - Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension
Pasquale Ambrosino, Tiziana Bachetti, Silvestro Ennio D’Anna, Brurya Galloway, Andrea Bianco, Vito D’Agnano, Antimo Papa, Andrea Motta, Fabio Perrotta, Mauro Maniscalco
Journal of Cardiovascular Development and Disease, 2022 - Endothelial Dysfunction in COVID‐19: A Unifying Mechanism and a Potential Therapeutic Target
Pasquale Ambrosino, Ilenia Lorenza Calcaterra, Marco Mosella, Roberto Formisano, Silvestro Ennio D’Anna, Tiziana Bachetti, Giuseppina Marcuccio, Brurya Galloway, Francesco Paolo Mancini, Antimo Papa, Andrea Motta, Matteo Nicola Dario Di Minno, Mauro Maniscalco
Biomedicines, 2022 - Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients
Pasquale Ambrosino, Paolo Parrella, Roberto Formisano, Giovanni Perrotta, Silvestro Ennio D’Anna, Marco Mosella, Antimo Papa, Mauro Maniscalco
Journal of Clinical Medicine, 2022 - Bacterial and viral infections and related inflammatory responses in chronic obstructive pulmonary disease
Silvestro Ennio D’Anna, Mauro Maniscalco, Francesco Cappello, Mauro Carone, Andrea Motta, Bruno Balbi, Fabio L. M. Ricciardolo, Gaetano Caramori, Antonino Di Stefano
Annals of Medicine, 2021 - A case scenario study on adherence to COPD GOLD recommendations by general practitioners in a rural area of southern Italy: The “progetto PADRE”
Mauro Maniscalco, Michele Martucci, Salvatore Fuschillo, Alberto de Felice, Silvestro Ennio D'Anna, Mario Cazzola
Respiratory Medicine, 2020 - Evaluation of innate immune mediators related to respiratory viruses in the lung of stable COPD patients
Silvestro E. D’Anna, Mauro Maniscalco, Vitina Carriero, Isabella Gnemmi, Gaetano Caramori, Francesco Nucera, Luisella Righi, Paola Brun, Bruno Balbi, Ian M Adcock, Maria Grazia Stella, Fabio L.M. Ricciardolo, Antonino Di Stefano
Journal of Clinical Medicine, 2020 - Bacterial–viral load and the immune response in stable and exacerbated COPD: Significance and therapeutic prospects
Silvestro D'Anna, Bruno Balbi, Francesco Cappello, Mauro Carone, Antonino Di Stefano
International Journal of Copd, 2016 - Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin
Simona Corrao, Rita Anzalone, Melania Lo Iacono, Tiziana Corsello, Antonino Di Stefano, Silvestro Ennio D'Anna, Bruno Balbi, Mauro Carone, Anna Sala, Davide Corona, Anna Maria Timperio, Lello Zolla, Felicia Farina, Everly Conway de Macario, Alberto J. L. Macario, Francesco Cappello, Giampiero La Rocca
Open Biology, 2014 - High-resolution computed tomography quantitation of emphysema is correlated with selected lung function values in stable COPD
Silvestro Ennio D’Anna, Roberto Asnaghi, Gaetano Caramori, Lorenzo Appendini, Manfredi Rizzo, Carmelo Cavallaro, Giorgio Marino, Francesco Cappello, Bruno Balbi, Antonino Di Stefano
Respiration, 2012 - Convergent sets of data from In Vivo and In Vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis
Francesco Cappello, Gaetano Caramori, Claudia Campanella, Chiara Vicari, Isabella Gnemmi, Andrea Zanini, Antonio Spanevello, Armando Capelli, Giampiero La Rocca, Rita Anzalone, Fabio Bucchieri, Silvestro Ennio D'Anna, Fabio L. M. Ricciardolo, Paola Brun, Bruno Balbi, Mauro Carone, Giovanni Zummo, Everly Conway de Macario, Alberto J. L. Macario, Antonino Di Stefano
Plos One, 2011 - T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients
A Di Stefano, G Caramori, I Gnemmi, M Contoli, C Vicari, A Capelli, F Magno, S E D'Anna, A Zanini, P Brun, P Casolari, K F Chung, P J Barnes, A Papi, I Adcock, B Balbi
Clinical and Experimental Immunology, 2009 - Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD
A Di Stefano, G Caramori, I Gnemmi, M Contoli, L Bristot, A Capelli, F L M Ricciardolo, F Magno, S E. D'Anna, A Zanini, M Carbone, F Sabatini, C Usai, P Brun, K F Chung, P J Barnes, A Papi, I M Adcock, B Balbi
Thorax, 2009 - HSP60 and HSP10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease
Francesco Cappello, Antonino Di Stefano, Sabrina David, Francesco Rappa, Rita Anzalone, Giampiero La Rocca, Silvestro E. D'Anna, Francesca Magno, Claudio F. Donner, Bruno Balbi, Giovanni Zummo
Cancer, 2006 - Immunopositivity of heat shock protein 60 as a biomarker of bronchial carcinogenesis
Francesco Cappello, Antonino Di Stefano, Silvestro E D'Anna, Claudio F Donner, Giovanni Zummo
Lancet Oncology, 2005 - Comparison of five bilevel pressure ventilators in patients with chronic ventilatory failure: A physiologic study
Michele Vitacca, Luca Barbano, Silvestro D’Anna, Roberto Porta, Luca Bianchi, Nicolino Ambrosino
Chest, 2002 - Lung function decline in bronchial asthma
Fabio Cibella, Giuseppina Cuttitta, Vincenzo Bellia, Salvatore Bucchieri, Silvestre D’Anna, Daniela Guerrera, Giovanni Bonsignore
Chest, 2002 - Is there evidence of airway inflammation in non-asthmatic athletes after running a marathon?
Journal of Sports Sciences, 2000
