Clinica di Malattie dellApparato Respiratorio

Pavia, Italy

Clinica di Malattie dellApparato Respiratorio

Pavia, Italy
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Cova E.,Clinica di Malattie dell'Apparato Respiratorio | Inghilleri S.,Clinica di Malattie dell'Apparato Respiratorio | Pandolfi L.,University of Milan Bicocca | Morosini M.,Clinica di Malattie dell'Apparato Respiratorio | And 16 more authors.
Nanotoxicology | Year: 2017

The use of gold nanoparticles (GNPs) as drug delivery system represents a promising issue for diseases without effective pharmacological treatment due to insufficient local drug accumulation and excessive systemic toxicity. Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic lung allograft dysfunction, the main challenge to long-term lung transplantation. It is believed that due to repeated insults to epithelial bronchiolar cells local inflammatory response creates a milieu that favors epithelial–mesenchymal transition and activation of local mesenchymal cells (MCs) leading to airway fibro-obliteration. In a previous work, we engineered GNPs loaded with the mammalian target of rapamycin inhibitor everolimus, specifically decorated with an antibody against CD44, a surface receptor expressed by primary MCs isolated from bronchoalveolar lavage of BOS patients. We proved in vitro that these GNPs (GNP-HCe) were able to specifically inhibit primary MCs without affecting the bronchial epithelial cell. In the present work, we investigated the effect of these bioengineered nanoconstructs on inflammatory cells, given that a stimulating effect on macrophages, neutrophils or lymphocytes is strongly unwanted in graft airways since it would foster fibrogenesis. In addition, we administered GNP-HCe by the inhalatory route to normal mice for a preliminary assessment of their pulmonary and peripheral (liver, spleen and kidney) uptake. By these experiments, an evaluation of tissue toxicity was also performed. The present study proves that our bioengineered nanotools do not rise an inflammatory response and, under the tested inhalatory conditions that were used, are non-toxic. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Balbi B.,I.R.C.C.S. Fondazione Salvatore Maugeri | Corda L.,U.O. di Medicina Generale | Ferrarotti I.,Clinica di Malattie dellApparato Respiratorio | Gatta N.,Associazione Nazionale ALFA 1 AT ONLUS | Luisetti M.,Clinica di Malattie dellApparato Respiratorio
Rassegna di Patologia dell'Apparato Respiratorio | Year: 2012

Introduction. Alpha-1 antitrypsin Deficiency (AATD) is a genetic disorder conferring increased risk of developing lung and liver disease. Its prevalence in Italy is not clearly ascertained but certainly there is a great discrepancy between expected and observed cases. Knowledge of a disease is a pre-condition to diagnose it. Aim of the present study was to ascertain the status of the knowledge on AATD among Italian Pulmonologists. Materials and methods. An electronic Survey on AATD was designed. The Survey was repeatedly electronically sent to 250 Heads of Pulmonary Departments in Italy between September and December 2011. It comprised a general and a specific part on AATD, including eight questions. Questions were focused on clinical characteristics, prevalence, diagnosis and treatment of pulmonary manifestations. For each question three answers were available, only one was correct. Results. Only 21.5% of pulmonologists participated to the Survey. The majority of participants gave a correct answer to questions regarding: clinical manifestations, % of subject with COPD affected by AATD, how to diagnose AATD, patients at risk of AATD to be tested for it, differences between treatment of COPD without vs. with AATD, indications to replacement therapy (RT) with exogenous AAT, GOLD stage in which RT is more effective, while the majority of participants thought that AATD in Europe is much rarer (1/20.000) than what is estimated to be (1/5.000). Discussion. The data show that Italian pulmonologists are aware of AATD and are knowledgeable about this condition. However, the response rate was low questioning the representativeness of the examined sample. In addition the majority of participant believe that AATD in Italy is much rarer than what expected from available genetic epidemiology data.


Sdanganelli A.,Clinica di Malattie dellApparato Respiratorio | Lusuardi M.,U.O. Riabilitazione Respiratoria | Soncini F.,University of Modena and Reggio Emilia | Maini M.,AUSL di Parma | And 10 more authors.
Rassegna di Patologia dell'Apparato Respiratorio | Year: 2014

Long-term oxygen therapy (LTOT) at home is an established treatment, which is potentially subjected to inappropriate prescription. This retrospective study aims to identify the determinants of inappropriate prescription through the analysis of existing prescribing information for LTOT and routes of supply within the Northern area of the Emilia-Romagna Region. We selected all first time prescriptions for LTOT released in 2009 in the provinces of Modena, Parma, Piacenza and Reggio Emilia. A specific questionnaire with data collection through an electronic database allowed to analyze both organizational / administrative and clinical variables related to LTOT prescription. We analyzed a total of 364 prescriptions: 62 from Modena, 96 from Parma, 73 from Reggio Emilia, and 133 from Piacenza. The data collected highlighted several differences in the prescribing process between the four provinces. Among the most frequently omitted information in the prescription we identified: a) values of PaO2 and PaCO2 (absent in more than 90% of prescriptions dispensed at the AUSL Modena, while present in about 70% of prescriptions in Parma and in almost all of those of Piacenza and Reggio Emilia); b) differential information on oxygen flow at night or during exercise (absent in the prescriptions from Parma, Modena and Piacenza and present in more than 60% of prescriptions from Reggio Emilia); c) indications concerning the follow-up (not covered in the prescriptions from Modena and Parma). Finally, definition of the diagnosis that justifies the need for prescription of LTOT is often missing or incomplete. Therefore the results of the study have allowed the identification of some factors of inappropriateness both on the clinical side and on the management side. This analysis indicates the need for interventions aimed at improving and standardizing the process of LTOT prescription.


Baldanti F.,Laboratori Sperimentali Of Ricerca | Rognoni V.,Laboratori Sperimentali Of Ricerca | Cascina A.,Clinica di Malattie dellApparato Respiratorio | Oggionni T.,Clinica di Malattie dellApparato Respiratorio | And 2 more authors.
Virology Journal | Year: 2011

Background: Post-transplant lymphoproliferative disorders (PTLD) are serious complications in lung transplant recipients. No consensus on EBV DNAemia levels predictive of PTLD has been reached. In addition, in many instances EBV DNAemia is determined in patients with suggestive symptoms only. Methods. The characteristics of five patients with PTLD as well as the prevalence of EBV DNAmia in a cohort of 137 consecutive patients receiving lung transplantation are described. Results: Twenty-six out of 137 patients (18.9%) were excluded from the analysis because lost at follow-up or dead from PTLD-independent reasons within three months of transplantation. EBV DNA in peripheral blood mononuclear cells (PBMC) was determined in 83/111 patients (74.8%) because of potential PTLD-related symptoms, while 28 patients (25.2%) showed no symptoms and were not examined. EBV DNAemia was positive in 53/83 patients (63.8%), and negative in 30/83 patients (36.2%). PTLD was diagnosed in five (4.5%) patients at a median time of 270 (range 120-870) days following transplantation. All five PTLD (three large B-cell lymphomas, one Hodgkin lymphoma and one possible pre-neoplastic lesion) were potentially associated with EBV infection. However, only 3/5 patients with PTLD had detectable EBV DNAemia: < 1,000 copies EBV DNA/1 × 10 5 PBMC in one patient and > 1,000 copies EBV DNA/1 × 10 5 PBMC in two patients. Conclusion: A systematic multidisciplinary (clinical, radiologic, virologic and histologic) approach is mandatory for the diagnosis and management of PTLD in lung transplant recipients, while monitoring of symptomatic patients only may provide an incomplete or late picture of the clinical problem. In addition, staining for EBV antigens and quantification of EBV DNA in biopsy specimens should always be performed to understand the role of EBV infection in the pathogenesis of PTLD. © 2011 Baldanti et al; licensee BioMed Central Ltd.


Cova E.,Clinica di Malattie dellApparato Respiratorio | Colombo M.,University of Milan Bicocca | Inghilleri S.,Clinica di Malattie dellApparato Respiratorio | Morosini M.,Clinica di Malattie dellApparato Respiratorio | And 10 more authors.
Nanomedicine | Year: 2015

Aims: Chronic lung allograft dysfunction represents the main cause of death after lung transplantation, and so far there is no effective therapy. Mesenchymal cells (MCs) are primarily responsible for fibrous obliteration of small airways typical of chronic lung allograft dysfunction. Here, we engineered gold nanoparticles containing a drug in the hydrophobic section to inhibit MCs, and exposing on the outer hydrophilic surface a monoclonal antibody targeting a MC-specific marker (half-chain gold nanoparticles with everolimus). Materials & methods: Half-chain gold nanoparticles with everolimus have been synthesized and incubated with MCs to evaluate the effect on proliferation and apoptosis. Results & discussion: Drug-loaded gold nanoparticles coated with the specific antibody were able to inhibit proliferation and induce apoptosis without stimulating an inflammatory response, as assessed by in vitro experiments. Conclusion: These findings demonstrate the effectiveness of our nanoparticles in inhibiting MCs and open new perspectives for a local treatment of chronic lung allograft dysfunction. © 2015 Future Medicine Ltd.


PubMed | Clinica di Malattie dellApparato Respiratorio
Type: Journal Article | Journal: Nanomedicine (London, England) | Year: 2015

Chronic lung allograft dysfunction represents the main cause of death after lung transplantation, and so far there is no effective therapy. Mesenchymal cells (MCs) are primarily responsible for fibrous obliteration of small airways typical of chronic lung allograft dysfunction. Here, we engineered gold nanoparticles containing a drug in the hydrophobic section to inhibit MCs, and exposing on the outer hydrophilic surface a monoclonal antibody targeting a MC-specific marker (half-chain gold nanoparticles with everolimus).Half-chain gold nanoparticles with everolimus have been synthesized and incubated with MCs to evaluate the effect on proliferation and apoptosis.Drug-loaded gold nanoparticles coated with the specific antibody were able to inhibit proliferation and induce apoptosis without stimulating an inflammatory response, as assessed by in vitro experiments.These findings demonstrate the effectiveness of our nanoparticles in inhibiting MCs and open new perspectives for a local treatment of chronic lung allograft dysfunction.

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