Fiorella Calabrese

University of Padova, Padova, Veneto, Italy

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Publications (120)639.79 Total impact

  • Fiorella Calabrese, Francesca Lunardi, Helmut Popper
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    ABSTRACT: The development of different molecular biology techniques in the past decade has led to an explosion of new research in molecular pathology with consequent important applications to diagnosis, prognosis, and therapeutics, as well as a clearer concept of the disease pathogenesis. Many methods used in molecular pathology are now validated and used in several areas of pathological diagnosis, particularly on infectious and neoplastic diseases. The spectrum of infectious diseases, especially lung infective diseases, is now broadening and modifying, thus the pathologist is increasingly involved in the diagnosis of these pathologies. The precise tissue characterization of lung infections has an important impact on specific therapeutic treatment. Increased knowledge of significant alterations in lung cancer has led today to a better understanding of the pathogenic substrate underlying the development, progression and metastasis of neoplastic processes. Molecular tests are now routinely performed in different lung tumors allowing a more precise patient stratification in terms of prognosis and therapy. This review focuses on molecular pathology of the principal infective lung diseases and tumors.
    Frontiers in bioscience (Landmark edition). 01/2015; 20:644-88.
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    ABSTRACT: Rationale: α1-antitrypsin (AAT) is a potent protease inhibitor which deficiency is associated with the presence of emphysema. An imbalance of elastase/antielastase, along with an innate inflammation in the lung, is believed to cause lung destruction in α1-antitrypsin deficiency (AATD). It is now apparent that AAT has important immune regulatory roles that would be lost in AATD, yet adaptive immune responses in the lung have not been investigated in patients with AATD. Objectives: To assess the adaptive immune response in severe AATD emphysema and compare it to that present in "usual" COPD . Methods: The immune inflammatory response in explanted lungs from 10 subjects with AATD was characterized and quantified and the results compared to 26 subjects with "usual" COPD, 17 smoking and 11 non-smoking controls with normal lung function. Results: Lymphoid follicles (LF) in AATD and "usual" COPD were markedly increased when compared to control groups. Molecular analysis of B-lymphocytes in LF showed predominantly mono/oligoclonality. LF number correlated with FEV1/FVC. B-lymphocytes, CD4+ and CD8+ T-lymphocytes were significantly increased in AATD and "usual" COPD when compared to control groups. IL-32, an important cytokine in induction of autoimmunity, was markedly upregulated in AATD and "usual" COPD. Conclusions: An important adaptive immune inflammation, comprising B, CD4+, CD8+ lymphocytes and mono/oligoclonal lymphoid follicles, is a prominent feature in AATD. These results change the paradigm of the mechanism of AATD-induced emphysema from a pure elastase/antielastase imbalance to a much more complex one involving the adaptive immune system, similarly to what occurs in "usual" COPD.
    American Journal of Respiratory and Critical Care Medicine 11/2014; · 11.99 Impact Factor
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    ABSTRACT: Objectives Adenocarcinoma comprises a group of diseases with heterogeneous clinical and molecular characteristics. COPD and lung cancer are strictly related; to date it is unknown if COPD-associated cancers have different features from tumours arising in non-COPD patients. Our aim was to study COPD-associated adenocarcinoma phenotypes mainly focusing on morphological and molecular aspects, in comparison to smoke-related cancer without COPD. Materials and Methods From 2010 to 2013, 54 patients with adenocarcinoma (20 COPD and 34 smokers) were prospectively studied. Each patient underwent a complete clinical and instrumental assessment. Morphological studies included analysis of growth pattern, cell proliferation (Ki-67/MIB1 expression) and parameters of intra-and peri-tumoural remodeling (inflammation, fibrosis and necrosis). Genetic analysis of EGFR and KRAS mutations was also performed. Results The two groups were comparable for the main demographic and biohumoral parameters except for increased blood basophil cell count in the COPD group. Compared to COPD, tumours of smokers presented an increased percentage of solid component (median: 20% vs 5%, p = 0.02), a reduced percentage of lepidic pattern (median: 0% vs 10%, p = 0.06) and higher Ki-67/MIB1 median value (55% vs 30%, p = 0.02). In multivariate analysis lepidic and solid histological pattern were significantly influenced by clinical group (p = 0.03 and 0.05, respectively). Concerning EGFR mutation, no differences were found between groups while KRAS mutation presented a trend of higher percentage in smokers compared to COPD (41% vs 20%, p = NS). Adenocarcinoma with KRAS mutation showed a higher value of Ki-67/MIB1 (65% vs 35%, p = 0.048) and prevalent solid pattern (35% vs 10%, p = 0.019) in comparison to wild-type form. Conclusions COPD-related adenocarcinoma presents molecular and morphological features of lower aggressiveness (increased lepidic component, reduced solid pattern, lower cell proliferation and less frequent KRAS mutation) compared to smokers. Different molecular mechanisms could be associated with the development of COPD associated cancer.
    Lung Cancer 10/2014; · 3.74 Impact Factor
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    ABSTRACT: Objectives To evaluate the role of CT and PET/CT in patients with thymic cancer and thymoma at initial staging.Methods We retrospectively reviewed CT and PET/CT scans of 26 patients with a thymic cancer (n=9) or thymoma (n=17). Chest CT findings documented were qualitative and quantitative. Both qualitative and semiquantitative data were recovered by PET/CT. The outcome of all patients was retrieved by clinical chart or follow-up. The comparisons among histological entities, outcome and qualitative data from CT and PET/CT were made by a non-parametric analysis.ResultsPET/CT resulted positive in 15/17 patients with thymoma. CT was available in 5/9 (56%) patients with thymic cancer and in 3/17 with thymoma. All quantitative CT parameters were significantly higher in patients with thymic cancer than thymoma (maximum axial diameter: 45vs.20mm, maximum longitudinal diameter: 69vs.21mm and volume: 77.91vs.4.52ml; all p<0.05). Conversely, only metabolic tumor volume (MTV) and total lesion glycolysis were significantly different in patients with thymic cancer than the counterpart (126.53vs.6.03cm3 and 246.05vs.20.32, respectively; both p<0.05). After a median follow-up time of 17.45 months, four recurrences of disease occurred: three in patients with thymic cancer and one with a type B2 thymoma. Follow-up data were lost in three subjects. CT volume in patients with recurrent disease was 102.19ml vs. a median value of 62.5ml in six disease-free patients. MTV was higher in recurrent than disease-free patient subset (143.3vs.81.13cm3), although not statistically significant (p=0.075).Conclusion From these preliminary results emerged that both morphological and metabolic volume can be useful from a diagnostic and prognostic point of view in thymic cancer and thymoma patients. A large multi-center clinical trial experience for confirming the findings of this study seems mandatory.
    Thoracic Cancer. 10/2014;
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    ABSTRACT: We analyzed 28 thymic epithelial tumors (TETs) using next-generation sequencing and identified a missense mutation (chromosome 7 c.74146970T>A) in GTF2I at high frequency in type A thymomas, a relatively indolent subtype. In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A and 74% of type AB thymomas but rarely in the aggressive subtypes, where recurrent mutations of known cancer genes have been identified. Therefore, GTF2I mutation correlated with better survival. GTF2I β and δ isoforms were expressed in TETs, and both mutant isoforms were able to stimulate cell proliferation in vitro. Thymic carcinomas carried a higher number of mutations than thymomas (average of 43.5 and 18.4, respectively). Notably, we identified recurrent mutations of known cancer genes, including TP53, CYLD, CDKN2A, BAP1 and PBRM1, in thymic carcinomas. These findings will complement the diagnostic assessment of these tumors and also facilitate development of a molecular classification and assessment of prognosis and treatment strategies.
    Nature Genetics 06/2014; · 29.65 Impact Factor
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    ABSTRACT: We report a rare case of an incidental diagnosis of necrotizing sarcoid granulomatosis (NSG) in a 60-year-old non smoker male. The patient was admitted to the hospital for sudden back pain. Chest X-ray revealed areas of parenchymal consolidation and high resolution computed tomography demonstrated a pulmonary nodular pattern without any lymph node enlargement. All laboratory and pulmonary function tests were normal. Bronchoscopy with bronchoalveolar lavage showed no sign of infection or specific inflammation. The diagnosis of NSG was made by histopathological examination of a lung surgical biopsy and by excluding other causes of granulomatous disease. In pauci/asymptomatic patients, as was our case, therapy is not necessary with a good prognosis and complete recovery. NSG is a rare systemic disease lying in between sarcoidosis and Wegener's granulomatosis with a benign clinical course that should always be kept in mind in patients with nodular pulmonary lesions even with subclinical or uncommon features.
    Respiratory care. 12/2013;
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    ABSTRACT: The physiological roles of the protease inhibitor SERPINB3 (SB3) are still largely unknown. The study was addressed to assess the biological effects of this serpin in vivo using a SB3 transgenic mouse model. Two colonies of mice (123 transgenic for SB3 and 148 C57BL/6J controls) have been studied. Transgenic (TG) mice showed longer survival than controls and the difference was more remarkable in males than in females (18.5% vs 12.7% life span increase). In TG mice decreased IL-6 in serum and lower p66shc in the liver were observed. In addition, TG males showed higher expression of mTOR in the liver. Liver histology showed age-dependent increase of steatosis and decrease of glycogen storage in both groups and none of the animals developed neoplastic lesions. In conclusion, the gain in life span observed in SB3-transgenic mice could be determined by multiple mechanisms, including the decrease of circulating IL-6 and the modulation of ageing genes in the liver.
    Scientific Reports 10/2013; 3:3056. · 5.08 Impact Factor
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    ABSTRACT: The physiological roles of the protease inhibitor SERPINB3 (SB3) are still largely unknown. The study was addressed to assess the biological effects of this serpin in vivo using a SB3 transgenic mouse model. Two colonies of mice (123 transgenic for SB3 and 148 C57BL/6J controls) have been studied. Transgenic (TG) mice showed longer survival than controls and the difference was more remarkable in males than in females (18.5% vs 12.7% life span increase). In TG mice decreased IL-6 in serum and lower p66shc in the liver were observed. In addition, TG males showed higher expression of mTOR in the liver. Liver histology showed age-dependent increase of steatosis and decrease of glycogen storage in both groups and none of the animals developed neoplastic lesions. In conclusion, the gain in life span observed in SB3-transgenic mice could be determined by multiple mechanisms, including the decrease of circulating IL-6 and the modulation of ageing genes in the liver.
    Scientific Reports 10/2013; · 5.08 Impact Factor
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    ABSTRACT: Immunological and histopathological features in pig-to-primate renal xenotransplantation are widely studied. Only limited data have been reported about clinicopathological findings in primate recipients of life-supporting renal xenografts. In human medicine, proteinuria represents a common complication in kidney transplantation and is associated with impaired graft survival. The detection of low molecular weight proteins of tubular origin is considered an early method for predicting potential graft rejection. In this study, the presence and the significance of quantitative and qualitative proteinuria were evaluated in xenotransplanted non-human primates in which kidney function was supported only by the transplanted organ. Eight bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) were transplanted with a single kidney from α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for human CD39, CD55, CD59, and α1,2-fucosyltransferase. In addition to hematological and biochemical analyses, quantitative and qualitative analysis of proteinuria was evaluated by urinary protein-to-creatinine ratio (UPC ratio) and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE), respectively. The main hematological and biochemical changes recorded after transplantation were a progressive anemia and a severe and progressive decrease in total proteins. In urine samples, the UPC ratio was low before transplantation and increased after transplantation. Similarly, SDS-AGE was negative before transplantation, but bands consistent with mixed (i.e., tubular and glomerular) proteinuria were observed in all samples collected post-transplantation. The study of clinicopathological changes in cynomolgus monkey renal xenograft recipients provides a valid help in monitoring the health conditions in the post-transplant period. Moreover, the evaluation of UPC ratio and the use of SDS-AGE technique in urine samples of cynomolgus monkey renal xenograft recipients may be considered a valid, inexpensive, and less time-consuming method than more sophisticated techniques in monitoring proteinuria. Proteinuria and presence of low molecular weight (LMW) proteins were consistently found in urine after transplantation, independent of fluctuations in renal function.
    Xenotransplantation 09/2013; · 1.78 Impact Factor
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    ABSTRACT: We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions. These findings provide a mechanistic clue to explain the switch to aerobic glycolysis of tumors and identify TRAP1 as a promising antineoplastic target.
    Cell metabolism 06/2013; 17(6):988-99. · 17.35 Impact Factor
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    ABSTRACT: Objectifs Cette étude réalisée en ouvert est basée sur une approche translationnelle dans le but de détecter les changements cliniques, à l’imagerie et des biomarqueurs synoviaux dans le liquide synovial (LS) et le tissu synovial (TS) dans la spondyloarthropathie périphérique (SpA) après l’inhibition intra-articulaire (IA) du tumor necrosis factor (TNF)-α par des injections répétées d’etanercept (E). Méthodes Vingt-sept patients présentant une synovite résistante du genou ont reçu quatre injections IA bihebdomadaires d’E (12,5 mg). Le critère d’évaluation principal était l’indice du genou de Thompson (THOMP) et les critères secondaires étaient représentés par l’indice articulaire du genou (IAG), la protéine C-réactive (CRP), le health assessment questionnaire-disability index (HAQ-DI), l’épaisseur maximale de la synoviale (EMS) évaluée par échographie et imagerie par résonnance magnétique (IRM) de contraste, le taux sérique des cellules mononucléaires dans les TS – CD45+ et – CD31+, le taux dans le LS d’interleukine-1β (IL-1β), le récepteur antagoniste de l’IL-1 (IL-1Ra) et d’IL-6 à l’inclusion et à la fin de l’étude. Résultats À la fin de l’étude, les données cliniques, de l’imagerie ainsi que les biomarqueurs ont été tous significativement réduits et améliorés comparativement aux données à l’inclusion. Il y avait une corrélation significative entre la clinique, l’imagerie et les biomarqueurs. (la CRP avec le THOMP, l’IAG, le HAQ-DI et le taux d’IL-1Ra ; l’EMS à l’écho avec l’IAG, le TS-CD45+ avec le THOMP, IAG, TS-CD31+ et LS-IL-1β ; le LS-IL-6 avec le THOMP, IAG, LS-IL-1β, ou IL-1Ra). Conclusions Cette étude en « preuve de concept » a démontré une amélioration précoce des scores locaux et systémiques, de l’épaisseur synoviale mesurée par IRM et échographie, et de l’expression des biomarqueurs synoviaux. Le CD45+, CD31+ dans le TS et l’IL-6 et IL-1β dans le LS peuvent être considérés comme des biomarqueurs potentiels dans la réponse de la SpA périphérique à un agent anti-TNF-α IA.
    Revue du Rhumatisme 03/2013; 80(2):149–156.
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    ABSTRACT: Pulmonary hypertension (PH) represents an important complication of idiopathic pulmonary fibrosis (IPF) with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68) induced pulmonary fibrosis was also assessed. Lung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP) and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice. A higher frequency of virus positive cases was found in IPF patients than in controls (0.0003) and only herpes virus genomes were detected. Viral cases showed higher mPAP (0.01), poorer performance in the six minute walking test (6MWT; 0.002) and higher frequency of primary graft (PGD) dysfunction after lung transplant (p = 0.02). Increased arterial thickening, particularly of the intimal layer (0.002 and 0.004) and higher TGF-β expression (0.002) were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells) in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (0.03), poorer performance in the 6MWT (0.008) and PGD ( = 0.02) after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients. Herpesviral infections may contribute to the development of PH in IPF patients.
    PLoS ONE 02/2013; 8(2):e55715. · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVES Alveolar air leaks represent a challenging problem in thoracic surgery, leading to increased patient morbidity and prolonged hospitalization. Several methods have been used, but no ideal technique exists yet. We investigated the lung-sealing capacity of an experimental kit for laser tissue welding.METHODS The kit is composed of a semiconductor laser system applied on a protein substrate associated with a chromophore that increases absorption. In vitro tests on porcine lung tissue were done to define ideal laser parameters (power 100 Å, frequency 50 Hz, pulse duration 400 µs) and protein substrate dilution (50%). For in vivo tests, through a left thoracotomy, 14 pigs received two different lung damages: a linear incision and a circular incision. Protein substrate applied on damaged areas was treated with laser to obtain a layer that reconstituted the integrity of the visceral pleura. Air leaks were intraoperatively evaluated by water submersion test with an airway pressure of 20 cmH(2)O. Animals were sacrificed at postoperative days 0 and 7 to study early and late pathological features.RESULTSAfter applying laser treatment, no air leaks were seen in all proofs except in 2 cases in which a second application was required. At time 0, pathological damage mostly consisted of superficial alveolar necrotic tissue covered by protein membrane. At time 7, a complete recovery of lung lesions by fibrous scar with slight inflammatory reaction of adjacent lung tissue was seen.CONCLUSIONS This experimental study demonstrated the effectiveness of laser tissue welding applied to seal air leaks after lung surgery. Further studies are needed to verify acceptability for human application.
    Interactive Cardiovascular and Thoracic Surgery 02/2013; · 1.11 Impact Factor
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    ABSTRACT: Acute liver failure (ALF) is characterized by severe neurological complications, known as acute hepatic encephalopathy, where brain ammonia and inflammatory processes play a dominant role. In experimental models of acute liver failure SERPINB3 was found significantly increased in microglia, the intrinsic immune cells of the central nervous system. The aim of the present study was to investigate the extent of brain tissue damage and the inflammatory milieu in experimental acute liver failure using a SERPINB3-transgenic mouse model. C57BL/6J wild-type and transgenic mice were inoculated with acetaminophen or phosphate-buffered saline and sacrificed 20 h postinjection. Proliferation and apoptotic activity were analyzed in brain tissue by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique. The expression of cytokines was analysed in brain and liver tissue by real time polymerase chain reaction and in the corresponding serum samples using a Bio-Plex system. Acetaminophen induced a significantly lower body temperature and shorter survival in transgenic than in wild-type mice, despite liver function was similar in both groups. The brain of transgenic mice, expressing SERPINB3 positivity in microglia, showed increased glial cell number, associated to significant lower apoptotic death events, compared with wild-type mice. In mice injected with acetaminophen, remarkably higher values of cytokines mRNA were observed in the liver of both groups, with a trend toward higher values in transgenic animals. In brain tissue similar increase of tumor necrosis factor-α was detected in transgenic and wild-type mice, while IL-10 mRNA increased only in the wild-type group. A remarkable increase of circulating Th1 cytokines was detected in serum of transgenic mice, while in the wild-type group they remained rather unchanged. These figures were associated with lower levels of granulocyte macropage colony-stimulating factor, despite similar increase of IL-10 values in both groups. In conclusion, in acute liver failure SERPINB3 determines an enhanced inflammatory background, mainly mediated by higher levels of Th1 proinflammatory cytokines.
    Experimental Biology and Medicine 12/2012; 237(12):1474-82. · 2.23 Impact Factor
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    ABSTRACT: In the WHO 1996 classification of cardiomyopathies, myocarditis is defined as an "inflammatory disease of the myocardium associated with cardiac dysfunction" and is listed among "specific cardiomyopathies". Myocarditis is diagnosed on endomyocardial biopsy (EMB) by established histological, immunological, and immunohistochemical criteria, and molecular techniques are recommended to identify viral etiology. Infectious, autoimmune, and idiopathic forms of inflammatory cardiomyopathy are recognized that may lead to dilated cardiomyopathy. According to Dallas criteria, myocarditis is diagnosed in the setting of an "inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes, not typical of ischemic damage associated with coronary artery disease". The majority of experts in the field agree that an actual increase in sensitivity of EMB has now been reached by using immunohistochemistry together with histology. A value of >14 leukocytes/mm(2) with the presence of T lymphocytes >7 cells/mm(2) has been considered a realistic cut off to reach a diagnosis of myocarditis. The development of molecular biological techniques, particularly amplification methods like polymerase chain reaction (PCR) or nested-PCR, allows the detection of low copy viral genomes even from an extremely small amount of tissue such as in EMB specimens. Positive PCR results obtained on EMB should always be accompanied by a parallel investigation on blood samples collected at the time of the EMB. According to the recent Association for European Cardiovascular Pathology guidelines, optimal specimen procurement and triage indicates at least three, preferably four, EMB fragments, each 1-2 mm in size, that should immediately be fixed in 10 % buffered formalin at room temperature for light microscopic examination. In expected focal myocardial lesions, additional sampling is recommended. Moreover, one or two specimens should be snap-frozen in liquid nitrogen and stored at -80 °C or alternatively stored in RNA-later for possible molecular tests or specific stains. A sample of peripheral blood (5-10 ml) in EDTA or citrate from patients with suspected myocarditis allows molecular testing for the same viral genomes sought in the myocardial tissue.
    Heart Failure Reviews 10/2012; · 3.99 Impact Factor
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    ABSTRACT: Background: Increased expression of ceramide has been detected in emphysema. Ceramide promotes autophagy and apoptosis, which concur with cellular homeostasis. Objectives: To determine whether ceramide expression is associated with the development of chronic obstructive pulmonary disease (COPD) and with altered cellular homeostasis in lung parenchyma. Methods: We studied 10 subjects with severe COPD, 13 with mild/moderate COPD, 11 with idiopathic pulmonary fibrosis (IPF), 12 non-COPD smokers, and 11 nonsmoking controls. The immunoreactivity for ceramide along with markers of autophagy (LC3B), apoptosis (cleaved caspase-3), and cell proliferation (MIB1) was quantified in alveolar walls. Results: Ceramide expression was increased in COPD patients compared with control smokers and was related to the impairment of gas exchange but not to the degree of airflow limitation. In COPD, an important activation of apoptosis and autophagy pathways was observed, particularly in patients with severe disease, that was not counterbalanced by cell proliferation. Upregulation of ceramide was observed even in subjects with IPF in whom activation of apoptosis and autophagy was negligible and cell proliferation was instead the most prominent feature. Conclusions: Ceramide expression, which is increased in COPD and even more so in IPF, appears to be neither specific nor related to COPD severity, probably representing a broader marker of lung damage. In contrast, apoptosis and autophagy are characteristics of the COPD pathology, particularly in its most severe stage.
    Respiration 09/2012; · 2.92 Impact Factor
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    ABSTRACT: BACKGROUND: Impaired immune response to viral infections in atopic asthmatic patients has been recently reported and debated. Whether this condition is present in childhood and whether it is affected by atopy per se deserves further investigation. OBJECTIVE: We sought to investigate airway interferon production in response to rhinovirus infection in children who are asthmatic, atopic, or both and its correlation with the airway inflammatory profile. METHODS: Bronchial biopsy specimens and epithelial cells were obtained from 47 children (mean age, 5 ± 0.5 years) undergoing bronchoscopy. The study population included asthmatic children who were either atopic or nonatopic, atopic children without asthma, and children without atopy or asthma. Rhinovirus type 16 induction of IFN-λ and IFN-β mRNA and protein levels was assessed in bronchial epithelial cell cultures. The immunoinflammatory profile was evaluated by means of immunohistochemistry in bronchial biopsy specimens. RESULTS: Rhinovirus type 16-induced interferon production was significantly reduced in atopic asthmatic, nonatopic asthmatic, and atopic nonasthmatic children compared with that seen in nonatopic nonasthmatic children (all P < .05). Increased rhinovirus viral RNA levels paralleled this deficient interferon induction. Additionally, IFN-λ and IFN-β induction correlated inversely with the airway T(H)2 immunopathologic profile (eosinophilia and IL-4 positivity: P < .05 and r = -0.38 and P < .05 and r = -0.58, respectively) and with epithelial damage (P < .05 and r = -0.55). Furthermore, total serum IgE levels correlated negatively with rhinovirus-induced IFN-λ mRNA levels (P < .05 and r = -0.41) and positively with rhinovirus viral RNA levels (P < .05 and r = 0.44). CONCLUSIONS: Deficient interferon responses to rhinovirus infection are present in childhood in asthmatic subjects irrespective of their atopic status and in atopic patients without asthma. These findings suggest that deficient immune responses to viral infections are not limited to patients with atopic asthma but are present in those with other T(H)2-oriented conditions.
    The Journal of allergy and clinical immunology 09/2012; · 12.05 Impact Factor
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    ABSTRACT: Diffuse lung diseases promote the development of vascular changes and pulmonary hypertension (PH). Endothelial progenitor cells (EPCs) seem to be involved in pulmonary vascular remodeling. We evaluated circulating and intra-pulmonary EPCs in end-stage lung diseases in relation to pulmonary arterial pressure (PAP). The study included 19 patients affected by different end-stage lung diseases, with or without PH. Six lung donors were considered as control group. EPCs were measured in blood samples taken at the time of transplant from pulmonary arteries and veins (by flow cytometry) as well as in lung specimen sections (by confocal microscopy) and expressed as percentage of total number of cells. The amount of EPC in lung specimens was significantly different according to type of disease (p = 0.001). Specifically, a higher number of EPCs was detected in idiopathic pulmonary hypertension and idiopathic pulmonary fibrosis with high (> 25 mm Hg) mean PAP (p = 0.03 for both) compared with chronic obstructive pulmonary disease and control group. There was a direct correlation between intrapulmonary EPCs and PAP. According to receiver operating characteristic curve analysis, the presence of > 3% EPCs had a 91% sensitivity and 93% specificity in identifying high mean PAP. There were no differences in circulating arterial or venous EPCs among groups. Intra-pulmonary EPCs are increased in lung diseases with high PAP, suggesting that EPCs may contribute to vascular remodeling in end-stage pulmonary disease.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2012; 31(9):1025-30. · 5.61 Impact Factor
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    ABSTRACT: OBJECTIVES: This open-label study is based on a translational approach with the aim of detecting changes in the clinical condition as well as in imaging and synovial biological markers in both synovial fluid (SF) and synovial tissue (ST) in peripheral spondyloarthritis (SpA) patients following intra-articular (IA) blockade of TNF-α by serial etanercept injections. METHODS: Twenty-seven SpA patients with resistant knee synovitis underwent four biweekly IA injections of etanercept (E) (12.5mg). The primary outcome of Thompson's Knee Index (THOMP), and secondary outcomes of Knee Joint Articular Index (KJAI), C-reactive protein (CRP), HAQ-Disability Index (HAQ-DI), maximal synovial thickness (MST) according to ultrasonography (US) and contrast-enhanced magnetic resonance (C+MR) imaging, ST-CD45+ mononuclear cells (MNC) and ST-CD31+ vessels, IL-1β, IL-1Ra and IL-6 levels in SF were assessed at baseline and at the end of the study. RESULTS: At the study end, clinical and imaging outcomes as well as ST and SF biological markers were significantly reduced compared to baseline. There were significant correlations between clinical, imaging and biological markers (CRP with either THOMP, or KJAI, or HAQ-DI or SF-IL-1Ra; US-MST with KJAI, ST-CD45+ with either THOMP, or KJAI, or ST-CD31+, or SF-IL-1β; SF-IL-6 with either THOMP, or KJAI, or SF-IL-1β, or IL-1Ra). CONCLUSIONS: The proof of concept study revealed early improvement either in local and systemic clinical scores, in synovial thickness measures by C+MR and US, or expression of synovial biological markers. CD45+, CD31+ in ST and IL-6 and IL-1β in SF may be considered potential biomarkers of the peripheral SpA response to IA TNF-α blocking.
    Joint, bone, spine: revue du rhumatisme 08/2012; · 2.25 Impact Factor
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    ABSTRACT: ABSTRACT BACKGROUND. D6 is an atypical chemokine receptor involved in chemokines degradation and resolution of acute inflammatory responses in mice. Emerging evidence suggests that D6 might behave differently in human chronic inflammatory conditions. We therefore investigated the involvement of D6 in the immune responses in COPD, a chronic inflammatory condition of the lung. METHODS. D6 expression was quantified by immunohistochemistry in surgical resected lung specimens from 16 patients with COPD (FEV1: 57 ± 6 % predicted) and 18 controls with normal lung function (9 smoking and 9 non-smoking). Bronchoalveolar lavage (BAL) was also obtained and analysed by flow cytometry, immunofluorescence, and molecular analysis for further assessment of D6 involvement. RESULTS. D6 expression in the lung was mainly detected in alveolar macrophages (AM). The percentage of D6+ AM was markedly increased in COPD patients as compared to both smoking and non-smoking controls (p<0.0005 for both). D6 expression was detected at both transcript and protein level in AM but not in monocyte-derived macrophages. Finally, D6 expression was positively correlated with markers of immune activation (CD8+ T lymphocytes, IL-32, TNFα, BAFF, phospho-p38 MAPK) and negatively with lung function (FEV1, FEV1/FVC). CONCLUSIONS. D6 is expressed in alveolar macrophages from COPD patients and its expression correlates with the degree of functional impairment and markers of immune activation. Up-regulation of D6 in alveolar macrophages could indicate that, besides its known scavenger activity in acute inflammation, D6 may have additional roles in chronic inflammatory conditions possibly promoting immune activation.
    Chest 07/2012; · 7.13 Impact Factor

Publication Stats

2k Citations
639.79 Total Impact Points


  • 1997–2013
    • University of Padova
      • • Department of Cardiac, Thoracic and Vascular Sciences
      • • Department of Medicine DIMED
      Padova, Veneto, Italy
  • 2007–2011
    • University-Hospital of Padova
      Padua, Veneto, Italy
  • 2009
    • Policlinico S.Orsola-Malpighi
      Bolonia, Emilia-Romagna, Italy
  • 2004
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      Chieta, Abruzzo, Italy
  • 2003
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy