Tiberio Oggionni - Academia.edu (original) (raw)

Papers by Tiberio Oggionni

Research paper thumbnail of Long-Term Off-Line Extracorporeal Photochemotherapy in Patients with Chronic Lung Allograft Rejection Not Responsive to Conventional Treatment: A 10-Year Single-Centre Analysis

Respiration, 2015

deaths (72.4%), of which 32 (76.2%) were CLAD related, over a median of 51 months (cumulative 3,0... more deaths (72.4%), of which 32 (76.2%) were CLAD related, over a median of 51 months (cumulative 3,066.5 person-months; p = 0.09). Among ECP patients, the FEV 1 slope flattened out after a decline in the initial months (slope -19 ml/month in months 0-6, +4 in months 36-48 and later; p = 0.001). RAS was associated with poorer survival, whereas a 'rapid decline in the previous 6 months' was not. No ECP side effects or complications were observed. Conclusion: Long-term ECP for CLAD is safe and reduces FEV 1 decline over time; the RAS phenotype might show a poorer response. ECP deserves to be evaluated in a randomized controlled trial.

Research paper thumbnail of T-lymphocyte subsets in lung transplant recipients: association between nadir CD4 T-cell count and viral infections after transplantation

Journal of Clinical Virology, 2015

Little is known about the kinetics of T-cell subsets in lung transplant recipients (LTR) and thei... more Little is known about the kinetics of T-cell subsets in lung transplant recipients (LTR) and their association with the occurrence of opportunistic infections (OI). To analyze the kinetics of T-lymphocyte subsets in LTR and the association between nadir CD4 T-cell count and viral infections after transplantation. Serial measurements of peripheral blood CD4 and CD8 T-cell counts obtained during the first year post-transplantation from 83 consecutive LTR and their correlation with both viral OI and community-acquired infections post-transplantation were retrospectively analyzed. LTR with a nadir CD4 T-cell count <200 cells/μl had consistently lower CD4 and CD8 T-cell counts than LTR with a nadir CD4 T-cell count >200 cells/μl (p<0.001). In LTR with a nadir CD4 T-cell count <200 cells/μl, the cumulative incidence of viral infections detected in peripheral blood and in bronchoalveolar lavage (BAL) samples was higher than in LTR with a nadir CD4 T-cell count >200 cells/μl (p=0.0012 and p=0.0058, respectively). A nadir CD4 T-cell count <200 cells/μl within the first three months post-transplantation predicted a higher frequency of viral infectious episodes in BAL samples within the subsequent six month period (p=0.0066). Stratification of patients according to nadir CD4 T-cell count may represent a new and simple approach for early identification of patients at risk for subsequent virus infections.

Research paper thumbnail of Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis

European journal of histochemistry : EJH

To investigate simultaneously localization and relative activity of MMPs during extracellular mat... more To investigate simultaneously localization and relative activity of MMPs during extracellular matrix (ECM) remodeling in bleomycin-induced pulmonary fibrosis in rat, we analyzed the time course of the expression, activity and/or concentration of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and TIMP-2, both in alveolar space (cellular and extracellular compartments) and in lung tissue. MMP and TIMP expression was detected (immunohistochemistry) in lung tissue. MMP activity (zymography) and TIMP concentration (ELISA) were evaluated in lung tissue homogenate (LTH), BAL supernatant (BALs) and BAL cell pellet (BALp) 3, 7, 14, and 28 days after bleomycin intratracheal instillation. Immunohistochemistry showed an extensive MMP and TIMP expression from day 7 in a wide range of structural and inflammatory cells in treated rats. MMP-2 was present mainly in epithelia, MMP-9 in inflammatory cells. MMP-2 and MMP-9 activity was increased respectively in BAL fluid and B...

Research paper thumbnail of The Italian register for diffuse infiltrative lung disorders (RIPID): a four-year report

Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders, 2005

RIPID (Italian register for diffuse infiltrative lung disorders) is a register aimed to create a ... more RIPID (Italian register for diffuse infiltrative lung disorders) is a register aimed to create a national database of diffuse infiltrative lung disorders, also known as interstitial lung diseases. The RIPID register collected prevalent data on patients affected by infiltrative diffuse lung disorders. The data form contains socio-demographic information (sex, age, years of education), existence in life, smoking habits, clinical data, diagnostic procedures (chest high resolution computed tomography (HRCT), bronchoalveolar lavage (BAL), transbronchial biopsies (TBB), surgical biopsies) and respiratory function tests at the time of diagnosis. Up to 18/01/2005 a total of 3152 patients had been included in the register. Seventy-nine centers and 138 physicians in all 20 regions of Italy contributed to patient enrolment. The vast majority of cases were from Northern Italy (2343 cases, 75%). The most frequently reported diagnoses were Sarcoidosis (1063 patients) and Idiopathic Pulmonary Fibr...

Research paper thumbnail of Incomplete expression of epithelial–mesenchymal transition markers in idiopathic pulmonary fibrosis

Pathology - Research and Practice, 2011

The hypothesis that epithelial-mesenchymal transition (EMT) contributes to the formation of fibro... more The hypothesis that epithelial-mesenchymal transition (EMT) contributes to the formation of fibroblast foci (FF), which are the histological hallmark and the site of active disease progression of Idiopathic Pulmonary Fibrosis (IPF), has not yet received a conclusive demonstration. Cells undergoing EMT lose epithelial features and acquire mesenchymal markers and morphology. Cadherin expression switch (from E to N) is one of the first events in EMT. We investigated the immunohistochemical expression of E- and N-cadherin, vimentin, fibronectin, laminin-5-γ2, α-smooth muscle actin, and fibroblast-specific protein-1 involved in EMT in 20 IPF lung biopsies, focusing on metaplastic squamous cells of bronchial basal origin, positive for laminin-5-γ2 and ΔNp63/p40, that cover FF. The results were compared with organizing pneumonia, reactive squamous cell metaplasia of bronchiolar epithelia, and squamous cell carcinoma. Bronchiolar basal metaplastic cells in IPF partially lost E-cadherin and expressed vimentin and fibronectin. Hyperplastic pneumocytes in IPF and controls coexpressed E-cadherin and N-cadherin, and were weakly positive for lam5-γ2. Reactive squamous cell metaplasia did not show any mesenchymal markers. Squamous cell carcinoma only expressed lam5-γ2. In IPF lungs, we observed two epithelial cell populations with a different expression profile of markers involved in EMT. Although neither hyperplastic pneumocytes nor bronchial basal cells showed evidence of complete EMT, only the latter seem to be specific for UIP and might have a role in its development.

Research paper thumbnail of Activation of Oncogenic Pathways in Idiopathic Pulmonary Fibrosis

Translational Oncology, 2014

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosi... more Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. The most recent hypotheses on IPF pathogenesis suggest a central role of epithelial cell damage, followed by a dysregulated molecular cross talk between epithelial cells and fibroblasts. Thus, IPF progression has often been assimilated to that of cancer, and several signaling patterns appear to be disrupted in both diseases. Here, we analyze the expression in an IPF series of a panel of molecules, which are known to play a role in tumorigenic process. Our findings, although preliminary, reveal that IPF landscape is enriched in neoplastic potential expressed in a context of complex genomic polyclonality and cellular heterogeneity. These results provide a rationale for further investigations aimed to exploit-in a similar fashion to cancer-targeted therapies for a "precision medicine" approach to IPF.

Research paper thumbnail of Regulatory CD4+CD25+ T cells in the peripheral blood of lung transplant recipients: correlation with transplant outcome

Research paper thumbnail of Incidence of Neoplastic Disease Following Lung Transplantation: A 17-Year Single-Center Experience

Transplantation Proceedings, 2011

Chronic immunosuppressive therapy following solid organ transplantation has been correlated with ... more Chronic immunosuppressive therapy following solid organ transplantation has been correlated with an increased risk of posttransplantation neoplastic disease (PTND). In this study we evaluated PTND incidence and outcome at our institution over a 17-year period among patients receiving lung transplantation. Between February 1992 and December 2008, we performed 290 lung transplantations in 280 patients, including 139 single (48% with 5 retransplantations), and 151 double lung transplantations (52% with 5 retransplantations). Among the 280 patients, 2 had undergone previous double lung transplantation in other hospitals. Follow-up of transplant recipients was performed up to December 2009. Forty-two patients died in the hospital, producing a cumulative early (30-day) mortality rate of 15%. Among the 238 patients discharged from the hospital who entered our follow-up program, 36 (15%) experienced PTND. The mean time between transplantation and diagnosis was 47 ± 42 months, and patients' mean age at time of diagnosis was 55 ± 14 years. Overall freedom from PTND was 97%, 84%, and 73% at 1, 5, and 10 years, respectively. PTND was considered to be the direct cause of death in 11 patients (30%). Overall survival of patients with PTND at five years (45%) did not differ from the remainder of the transplanted population (46%). However, PTND became a relevant cause of death in the long-term (>5 years) follow-up. Our experience confirms that PTND was frequently diagnosed following lung transplantation. Even if PTND did not seem to significantly affect the survival of patients undergoing lung transplantation, it may become a significant cause of death among those surviving beyond 5 years.

Research paper thumbnail of Risk Factors for Chronic Renal Dysfunction in Lung Transplant Recipients

Transplantation, 2007

Several factors predispose to renal dysfunction (RD), a common complication of solid organ transp... more Several factors predispose to renal dysfunction (RD), a common complication of solid organ transplants. We evaluated the impact of clinical and laboratory parameters on the decline of renal function in lung and heart-lung transplant recipients. We enrolled 45 patients who survived more than 6 months after transplantation, had normal renal function and urinalysis before the surgery. The prognostic value of variables for the occurrence of RD was calculated by univariate analysis. Thirty patients developed RD, defined as doubling of serum creatinine or creatinine steadily Ͼ1.5 mg/dL after a median time of 12 months. Serum creatinine above 0.9 mg/dL during the month preceding lung transplant, systolic blood pressure above 130 mmHg, and pretransplant idiopathic pulmonary hypertension were significantly associated with the development of RD. Our findings indicate that increased systolic blood pressure, reduced glomerular filtration rate, and idiopathic pulmonary hypertension are risk factors for chronic RD in lung transplant recipients.

Research paper thumbnail of Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients

Journal of Medical Virology, 2006

Research paper thumbnail of 62: Outcomes Following Lung Transplantation for Pulmonary Hypertension Secondary to Hereditary Hemorrhagic Telangiectasia

The Journal of Heart and Lung Transplantation, 2008

Research paper thumbnail of 37: Incidence of Upper and Lower Airway Viral Infections in a Cohort of Lung Transplant Recipients (LTRs)

The Journal of Heart and Lung Transplantation, 2008

Purpose: Lung transplant (LTx) recipients are at risk for virus infections and reactivations. The... more Purpose: Lung transplant (LTx) recipients are at risk for virus infections and reactivations. The frequency of Epstein-Barr virus (EBV) cytomegalovirus (CMV) and adenovirus (HAdV) infections and reactivations, clinical symptoms and outcome were prospectively assessed in LTx recipients. Methods and Materials: 101 consecutive LTx patients at Hannover Medical School were included in the study from June 2005 to July 2006 and were weekly monitored for clinical symptoms for one to 21 weeks after LTx (median 4 weeks). CMV pp65 antigen and EBV and HAdV DNA by quantitative PCR were determined in blood. Univariable analysis was performed. Results: Prior to LTx 97 % of the patients were EBV-IgG positive and 60 % were CMV-IgG positive. 475 peripheral blood specimens of 101 patients were examined. EBV was detected in peripheral blood in 42 (41.6 %) patients at least once. All EBV DNAemic patients were EBV-IgG positive prior to LTx. Virus load of EBV DNAemic patients was 2000 copies per ml peripheral blood in median and ranged from 900 to 45000 copies per ml. No post transplant lymphoproliferative disease occurred. Even though all patients received antiviral prophylaxis CMV pp65 antigen was detected in 7 (6.9 %) patients of which two had primary infection. HAdV DNA was detected in 2 (2 %) patients.

Research paper thumbnail of Bronchoalveolar lavage cytokine profile in a cohort of lung transplant recipients: A predictive role of interleukin-12 with respect to onset of bronchiolitis obliterans syndrome

The Journal of Heart and Lung Transplantation, 2004

Background: Bronchiolitis obliterans syndrome is the main long-term complication of lung transpla... more Background: Bronchiolitis obliterans syndrome is the main long-term complication of lung transplantation that limits survival of lung transplant patients. Its pathophysiologic mechanisms are still poorly understood but it seems to result from a chronic immunologic/inflammatory insult leading to excessive fibroproliferation. The aim of this longitudinal study of 44 lung recipients was to determine whether a number of bronchoalveolar lavage and clinical variables are associated with a higher risk of developing bronchiolitis obliterans syndrome.

Research paper thumbnail of Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation

The Journal of Heart and Lung Transplantation, 2002

Encouraging results in transplantation of other solid organs led to investigation of the use of t... more Encouraging results in transplantation of other solid organs led to investigation of the use of tacrolimus in lung transplantation as a salvage immunosuppressant in persistent acute rejection.

Research paper thumbnail of 155: Clinical and Immunological Evaluation of Azithromycin in Bronchiolitis Obliterans Syndrome (BOS) after Lung Transplantation

The Journal of Heart and Lung Transplantation, 2009

Research paper thumbnail of 656: Survival Following Single Lung Transplant for Pulmonary Fibrosis: Satisfactory Results in Our 16-Years Single Centre Experience

The Journal of Heart and Lung Transplantation, 2009

Purpose: For pediatric lung transplant and adult lung transplantation, the largest obstacle to lo... more Purpose: For pediatric lung transplant and adult lung transplantation, the largest obstacle to long-term survival remains chronic allograft rejection secondary to the development of bronchiolitis obliterans, for which little advancement has been made in prevention or treatment.The aim of this study was to test whether donor and recipient age influence the development of obliterative airway disease in an established rat model of human bronchiolitis obliterans.

Research paper thumbnail of 655: Incidence of De Novo Malignancies in Lung Transplant Recipients in Italy: A Single-Institution Experience, 1991-2008

The Journal of Heart and Lung Transplantation, 2009

Purpose: For pediatric lung transplant and adult lung transplantation, the largest obstacle to lo... more Purpose: For pediatric lung transplant and adult lung transplantation, the largest obstacle to long-term survival remains chronic allograft rejection secondary to the development of bronchiolitis obliterans, for which little advancement has been made in prevention or treatment.The aim of this study was to test whether donor and recipient age influence the development of obliterative airway disease in an established rat model of human bronchiolitis obliterans.

Research paper thumbnail of SPHERIC-1 (Sildenafil and Pulmonary HypERtension in COPD): Intention-to-Treat (ITT) Analysis of Safety and Efficacy Data

The Journal of Heart and Lung Transplantation, 2014

Research paper thumbnail of 155: Clinical benefit of chronic low dose azythromycin treatment in patients with bronchiolitis obliterans

The Journal of Heart and Lung Transplantation, 2007

While these data are preliminary, the diagnosis of alveolar duct fibrosis (ADF) in TBB was strong... more While these data are preliminary, the diagnosis of alveolar duct fibrosis (ADF) in TBB was strongly associated with BOS/OB in this cohort of LTRs. ADF was present prior to the diagnosis of BOS/OB in the majority of LTRs, and within a year of BOS onset in a third of that subgroup. This suggests a potential role for ADF as a surrogate predictive marker of chronic allograft rejection.

Research paper thumbnail of Bronchoalveolar Lavage Fluid Proteome in Bronchiolitis Obliterans Syndrome: Possible Role for Surfactant Protein A in Disease Onset

The Journal of Heart and Lung Transplantation, 2007

Background: Bronchiolitis obliterans syndrome (BOS) affects long-term survival of lung transplant... more Background: Bronchiolitis obliterans syndrome (BOS) affects long-term survival of lung transplant (Tx) recipients (LTRs), with no consistently effective treatment strategy. Identifying early markers of BOS is of paramount importance for improving graft survival.

Research paper thumbnail of Long-Term Off-Line Extracorporeal Photochemotherapy in Patients with Chronic Lung Allograft Rejection Not Responsive to Conventional Treatment: A 10-Year Single-Centre Analysis

Respiration, 2015

deaths (72.4%), of which 32 (76.2%) were CLAD related, over a median of 51 months (cumulative 3,0... more deaths (72.4%), of which 32 (76.2%) were CLAD related, over a median of 51 months (cumulative 3,066.5 person-months; p = 0.09). Among ECP patients, the FEV 1 slope flattened out after a decline in the initial months (slope -19 ml/month in months 0-6, +4 in months 36-48 and later; p = 0.001). RAS was associated with poorer survival, whereas a 'rapid decline in the previous 6 months' was not. No ECP side effects or complications were observed. Conclusion: Long-term ECP for CLAD is safe and reduces FEV 1 decline over time; the RAS phenotype might show a poorer response. ECP deserves to be evaluated in a randomized controlled trial.

Research paper thumbnail of T-lymphocyte subsets in lung transplant recipients: association between nadir CD4 T-cell count and viral infections after transplantation

Journal of Clinical Virology, 2015

Little is known about the kinetics of T-cell subsets in lung transplant recipients (LTR) and thei... more Little is known about the kinetics of T-cell subsets in lung transplant recipients (LTR) and their association with the occurrence of opportunistic infections (OI). To analyze the kinetics of T-lymphocyte subsets in LTR and the association between nadir CD4 T-cell count and viral infections after transplantation. Serial measurements of peripheral blood CD4 and CD8 T-cell counts obtained during the first year post-transplantation from 83 consecutive LTR and their correlation with both viral OI and community-acquired infections post-transplantation were retrospectively analyzed. LTR with a nadir CD4 T-cell count <200 cells/μl had consistently lower CD4 and CD8 T-cell counts than LTR with a nadir CD4 T-cell count >200 cells/μl (p<0.001). In LTR with a nadir CD4 T-cell count <200 cells/μl, the cumulative incidence of viral infections detected in peripheral blood and in bronchoalveolar lavage (BAL) samples was higher than in LTR with a nadir CD4 T-cell count >200 cells/μl (p=0.0012 and p=0.0058, respectively). A nadir CD4 T-cell count <200 cells/μl within the first three months post-transplantation predicted a higher frequency of viral infectious episodes in BAL samples within the subsequent six month period (p=0.0066). Stratification of patients according to nadir CD4 T-cell count may represent a new and simple approach for early identification of patients at risk for subsequent virus infections.

Research paper thumbnail of Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis

European journal of histochemistry : EJH

To investigate simultaneously localization and relative activity of MMPs during extracellular mat... more To investigate simultaneously localization and relative activity of MMPs during extracellular matrix (ECM) remodeling in bleomycin-induced pulmonary fibrosis in rat, we analyzed the time course of the expression, activity and/or concentration of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and TIMP-2, both in alveolar space (cellular and extracellular compartments) and in lung tissue. MMP and TIMP expression was detected (immunohistochemistry) in lung tissue. MMP activity (zymography) and TIMP concentration (ELISA) were evaluated in lung tissue homogenate (LTH), BAL supernatant (BALs) and BAL cell pellet (BALp) 3, 7, 14, and 28 days after bleomycin intratracheal instillation. Immunohistochemistry showed an extensive MMP and TIMP expression from day 7 in a wide range of structural and inflammatory cells in treated rats. MMP-2 was present mainly in epithelia, MMP-9 in inflammatory cells. MMP-2 and MMP-9 activity was increased respectively in BAL fluid and B...

Research paper thumbnail of The Italian register for diffuse infiltrative lung disorders (RIPID): a four-year report

Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders, 2005

RIPID (Italian register for diffuse infiltrative lung disorders) is a register aimed to create a ... more RIPID (Italian register for diffuse infiltrative lung disorders) is a register aimed to create a national database of diffuse infiltrative lung disorders, also known as interstitial lung diseases. The RIPID register collected prevalent data on patients affected by infiltrative diffuse lung disorders. The data form contains socio-demographic information (sex, age, years of education), existence in life, smoking habits, clinical data, diagnostic procedures (chest high resolution computed tomography (HRCT), bronchoalveolar lavage (BAL), transbronchial biopsies (TBB), surgical biopsies) and respiratory function tests at the time of diagnosis. Up to 18/01/2005 a total of 3152 patients had been included in the register. Seventy-nine centers and 138 physicians in all 20 regions of Italy contributed to patient enrolment. The vast majority of cases were from Northern Italy (2343 cases, 75%). The most frequently reported diagnoses were Sarcoidosis (1063 patients) and Idiopathic Pulmonary Fibr...

Research paper thumbnail of Incomplete expression of epithelial–mesenchymal transition markers in idiopathic pulmonary fibrosis

Pathology - Research and Practice, 2011

The hypothesis that epithelial-mesenchymal transition (EMT) contributes to the formation of fibro... more The hypothesis that epithelial-mesenchymal transition (EMT) contributes to the formation of fibroblast foci (FF), which are the histological hallmark and the site of active disease progression of Idiopathic Pulmonary Fibrosis (IPF), has not yet received a conclusive demonstration. Cells undergoing EMT lose epithelial features and acquire mesenchymal markers and morphology. Cadherin expression switch (from E to N) is one of the first events in EMT. We investigated the immunohistochemical expression of E- and N-cadherin, vimentin, fibronectin, laminin-5-γ2, α-smooth muscle actin, and fibroblast-specific protein-1 involved in EMT in 20 IPF lung biopsies, focusing on metaplastic squamous cells of bronchial basal origin, positive for laminin-5-γ2 and ΔNp63/p40, that cover FF. The results were compared with organizing pneumonia, reactive squamous cell metaplasia of bronchiolar epithelia, and squamous cell carcinoma. Bronchiolar basal metaplastic cells in IPF partially lost E-cadherin and expressed vimentin and fibronectin. Hyperplastic pneumocytes in IPF and controls coexpressed E-cadherin and N-cadherin, and were weakly positive for lam5-γ2. Reactive squamous cell metaplasia did not show any mesenchymal markers. Squamous cell carcinoma only expressed lam5-γ2. In IPF lungs, we observed two epithelial cell populations with a different expression profile of markers involved in EMT. Although neither hyperplastic pneumocytes nor bronchial basal cells showed evidence of complete EMT, only the latter seem to be specific for UIP and might have a role in its development.

Research paper thumbnail of Activation of Oncogenic Pathways in Idiopathic Pulmonary Fibrosis

Translational Oncology, 2014

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosi... more Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. The most recent hypotheses on IPF pathogenesis suggest a central role of epithelial cell damage, followed by a dysregulated molecular cross talk between epithelial cells and fibroblasts. Thus, IPF progression has often been assimilated to that of cancer, and several signaling patterns appear to be disrupted in both diseases. Here, we analyze the expression in an IPF series of a panel of molecules, which are known to play a role in tumorigenic process. Our findings, although preliminary, reveal that IPF landscape is enriched in neoplastic potential expressed in a context of complex genomic polyclonality and cellular heterogeneity. These results provide a rationale for further investigations aimed to exploit-in a similar fashion to cancer-targeted therapies for a "precision medicine" approach to IPF.

Research paper thumbnail of Regulatory CD4+CD25+ T cells in the peripheral blood of lung transplant recipients: correlation with transplant outcome

Research paper thumbnail of Incidence of Neoplastic Disease Following Lung Transplantation: A 17-Year Single-Center Experience

Transplantation Proceedings, 2011

Chronic immunosuppressive therapy following solid organ transplantation has been correlated with ... more Chronic immunosuppressive therapy following solid organ transplantation has been correlated with an increased risk of posttransplantation neoplastic disease (PTND). In this study we evaluated PTND incidence and outcome at our institution over a 17-year period among patients receiving lung transplantation. Between February 1992 and December 2008, we performed 290 lung transplantations in 280 patients, including 139 single (48% with 5 retransplantations), and 151 double lung transplantations (52% with 5 retransplantations). Among the 280 patients, 2 had undergone previous double lung transplantation in other hospitals. Follow-up of transplant recipients was performed up to December 2009. Forty-two patients died in the hospital, producing a cumulative early (30-day) mortality rate of 15%. Among the 238 patients discharged from the hospital who entered our follow-up program, 36 (15%) experienced PTND. The mean time between transplantation and diagnosis was 47 ± 42 months, and patients' mean age at time of diagnosis was 55 ± 14 years. Overall freedom from PTND was 97%, 84%, and 73% at 1, 5, and 10 years, respectively. PTND was considered to be the direct cause of death in 11 patients (30%). Overall survival of patients with PTND at five years (45%) did not differ from the remainder of the transplanted population (46%). However, PTND became a relevant cause of death in the long-term (>5 years) follow-up. Our experience confirms that PTND was frequently diagnosed following lung transplantation. Even if PTND did not seem to significantly affect the survival of patients undergoing lung transplantation, it may become a significant cause of death among those surviving beyond 5 years.

Research paper thumbnail of Risk Factors for Chronic Renal Dysfunction in Lung Transplant Recipients

Transplantation, 2007

Several factors predispose to renal dysfunction (RD), a common complication of solid organ transp... more Several factors predispose to renal dysfunction (RD), a common complication of solid organ transplants. We evaluated the impact of clinical and laboratory parameters on the decline of renal function in lung and heart-lung transplant recipients. We enrolled 45 patients who survived more than 6 months after transplantation, had normal renal function and urinalysis before the surgery. The prognostic value of variables for the occurrence of RD was calculated by univariate analysis. Thirty patients developed RD, defined as doubling of serum creatinine or creatinine steadily Ͼ1.5 mg/dL after a median time of 12 months. Serum creatinine above 0.9 mg/dL during the month preceding lung transplant, systolic blood pressure above 130 mmHg, and pretransplant idiopathic pulmonary hypertension were significantly associated with the development of RD. Our findings indicate that increased systolic blood pressure, reduced glomerular filtration rate, and idiopathic pulmonary hypertension are risk factors for chronic RD in lung transplant recipients.

Research paper thumbnail of Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients

Journal of Medical Virology, 2006

Research paper thumbnail of 62: Outcomes Following Lung Transplantation for Pulmonary Hypertension Secondary to Hereditary Hemorrhagic Telangiectasia

The Journal of Heart and Lung Transplantation, 2008

Research paper thumbnail of 37: Incidence of Upper and Lower Airway Viral Infections in a Cohort of Lung Transplant Recipients (LTRs)

The Journal of Heart and Lung Transplantation, 2008

Purpose: Lung transplant (LTx) recipients are at risk for virus infections and reactivations. The... more Purpose: Lung transplant (LTx) recipients are at risk for virus infections and reactivations. The frequency of Epstein-Barr virus (EBV) cytomegalovirus (CMV) and adenovirus (HAdV) infections and reactivations, clinical symptoms and outcome were prospectively assessed in LTx recipients. Methods and Materials: 101 consecutive LTx patients at Hannover Medical School were included in the study from June 2005 to July 2006 and were weekly monitored for clinical symptoms for one to 21 weeks after LTx (median 4 weeks). CMV pp65 antigen and EBV and HAdV DNA by quantitative PCR were determined in blood. Univariable analysis was performed. Results: Prior to LTx 97 % of the patients were EBV-IgG positive and 60 % were CMV-IgG positive. 475 peripheral blood specimens of 101 patients were examined. EBV was detected in peripheral blood in 42 (41.6 %) patients at least once. All EBV DNAemic patients were EBV-IgG positive prior to LTx. Virus load of EBV DNAemic patients was 2000 copies per ml peripheral blood in median and ranged from 900 to 45000 copies per ml. No post transplant lymphoproliferative disease occurred. Even though all patients received antiviral prophylaxis CMV pp65 antigen was detected in 7 (6.9 %) patients of which two had primary infection. HAdV DNA was detected in 2 (2 %) patients.

Research paper thumbnail of Bronchoalveolar lavage cytokine profile in a cohort of lung transplant recipients: A predictive role of interleukin-12 with respect to onset of bronchiolitis obliterans syndrome

The Journal of Heart and Lung Transplantation, 2004

Background: Bronchiolitis obliterans syndrome is the main long-term complication of lung transpla... more Background: Bronchiolitis obliterans syndrome is the main long-term complication of lung transplantation that limits survival of lung transplant patients. Its pathophysiologic mechanisms are still poorly understood but it seems to result from a chronic immunologic/inflammatory insult leading to excessive fibroproliferation. The aim of this longitudinal study of 44 lung recipients was to determine whether a number of bronchoalveolar lavage and clinical variables are associated with a higher risk of developing bronchiolitis obliterans syndrome.

Research paper thumbnail of Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation

The Journal of Heart and Lung Transplantation, 2002

Encouraging results in transplantation of other solid organs led to investigation of the use of t... more Encouraging results in transplantation of other solid organs led to investigation of the use of tacrolimus in lung transplantation as a salvage immunosuppressant in persistent acute rejection.

Research paper thumbnail of 155: Clinical and Immunological Evaluation of Azithromycin in Bronchiolitis Obliterans Syndrome (BOS) after Lung Transplantation

The Journal of Heart and Lung Transplantation, 2009

Research paper thumbnail of 656: Survival Following Single Lung Transplant for Pulmonary Fibrosis: Satisfactory Results in Our 16-Years Single Centre Experience

The Journal of Heart and Lung Transplantation, 2009

Purpose: For pediatric lung transplant and adult lung transplantation, the largest obstacle to lo... more Purpose: For pediatric lung transplant and adult lung transplantation, the largest obstacle to long-term survival remains chronic allograft rejection secondary to the development of bronchiolitis obliterans, for which little advancement has been made in prevention or treatment.The aim of this study was to test whether donor and recipient age influence the development of obliterative airway disease in an established rat model of human bronchiolitis obliterans.

Research paper thumbnail of 655: Incidence of De Novo Malignancies in Lung Transplant Recipients in Italy: A Single-Institution Experience, 1991-2008

The Journal of Heart and Lung Transplantation, 2009

Purpose: For pediatric lung transplant and adult lung transplantation, the largest obstacle to lo... more Purpose: For pediatric lung transplant and adult lung transplantation, the largest obstacle to long-term survival remains chronic allograft rejection secondary to the development of bronchiolitis obliterans, for which little advancement has been made in prevention or treatment.The aim of this study was to test whether donor and recipient age influence the development of obliterative airway disease in an established rat model of human bronchiolitis obliterans.

Research paper thumbnail of SPHERIC-1 (Sildenafil and Pulmonary HypERtension in COPD): Intention-to-Treat (ITT) Analysis of Safety and Efficacy Data

The Journal of Heart and Lung Transplantation, 2014

Research paper thumbnail of 155: Clinical benefit of chronic low dose azythromycin treatment in patients with bronchiolitis obliterans

The Journal of Heart and Lung Transplantation, 2007

While these data are preliminary, the diagnosis of alveolar duct fibrosis (ADF) in TBB was strong... more While these data are preliminary, the diagnosis of alveolar duct fibrosis (ADF) in TBB was strongly associated with BOS/OB in this cohort of LTRs. ADF was present prior to the diagnosis of BOS/OB in the majority of LTRs, and within a year of BOS onset in a third of that subgroup. This suggests a potential role for ADF as a surrogate predictive marker of chronic allograft rejection.

Research paper thumbnail of Bronchoalveolar Lavage Fluid Proteome in Bronchiolitis Obliterans Syndrome: Possible Role for Surfactant Protein A in Disease Onset

The Journal of Heart and Lung Transplantation, 2007

Background: Bronchiolitis obliterans syndrome (BOS) affects long-term survival of lung transplant... more Background: Bronchiolitis obliterans syndrome (BOS) affects long-term survival of lung transplant (Tx) recipients (LTRs), with no consistently effective treatment strategy. Identifying early markers of BOS is of paramount importance for improving graft survival.