Role of SP-A gene polymorphism in lung transplantation

Lung transplantation is a widely accepted therapeutic option for end stage lung disease. Clinical outcome is yet challenged by primary graft failure responsible for the majority of the early mortality, by chronic allograft dysfunction and chronic rejection accounting for more than 30% of deaths after the third postoperative year. Pulmonary surfactant proteins (SP) A, B, C and D are one of the first host defense mechanisms the lung can mount. SP-A in particular, produced by the type II pneumocytes, is active in the innate and adaptive immune system being an opsonin, but also regulating the macrophage and lymphocyte response. The main hypothesis for this project is that pulmonary surfactant protein A polymorphism may determine the early and long term lung allograft survival. Of note SP-A biologic activity seems to be genetically determined and SP-A polymorphisms have been associated to various lung disease. The two SP-A genes SP-A1 and SP-A2 have several polymorphisms within the coding region, SP-A1 (6A, 6A2-20), and SP-A2(1A, 1A0-13). The SP-A gene expression is regulated by cAMP, TTF-1 and glucocorticoids. In vitro studies have indicated that SP-A1 and SP-A2 gene variants may have a variable response to glucocorticoids. We proposed to determine if SP-A gene polymorphism predicts primary graft dysfunction and/or chronic lung allograft dysfunction and if SP-A may serve as a biomarker of lung allograft dysfunction. We also proposed to study the interaction between immunosuppressive drugs and SP-A expression and determine whether this is dependent on SP-A polymorphisms. This study will generate novel information improving our understanding of lung allograft dysfunction. It is conceivable that the information will stimulate the interest for a multi centre study to investigate if SP-A polymorphism may be integrated in the donor lung selection criteria and/or to implement post transplant tailored immunosuppression.

Timing per l'inserimento in lista dei pazienti affetti da fibrosi cistica che necessitano di trapianto polmonare: casistica di un centro regionale di riferimento

Timing of waiting list entrance for patients with cystic fibrosis in need of pulmonary transplant: the experience of a regional referral centre Objective: Evaluation of parameters that can predict a rapid decay of general conditions of patients affected by Cystic Fibrosis (CF) with no specific criteria to be candidate to pulmonary transplant. Material and methods: Fifteen patients with CF who died for complications and 8 who underwent lung transplantation in the 2000-2010 decade, were enrolled. Clinical data 2 years before the event (body max index, FEV1%, number of EV antibiotic treatments per year, colonization with Methicillin-resistant Staphylococcus aureus (MRSA), pseudomonas aeruginosa mucosus, burkholderia cepacia, pulmonary allergic aspergilosis) were compared among the 2 groups. Results: Mean FEV1% was significantly higher and mean number of antibiotic treatment was lower in deceased than in the transplanted patients (p<0.002 and p<0.001 respectively). Although in patients who died there were no including criteria to enter the transplant list 2 years before the exitus, suggestive findings such as low BMI (17.3), high incidence of hepatic pathology (33.3%), diabetes (50%), and infections with MRSA infection (25%), Pseudomonas aeruginosa (83.3%) and burkholderia cepacia (8.3%) were found with no statistical difference with transplanted patients, suggesting those patients were at risk of severe prognosis. In patients who died, females were double than males. Conclusion: While evaluating patients with CF, negative prognostic factors such as the ones investigated in this study, should be considered to select individuals with high mortality risk who need stricter therapeutical approach and follow up. Inclusion of those patients in the transplant waiting list should be taken into account.

Metodiche di preservazione del polmone isolato per lo studio ecografico: Studio sperimentale

Oggetto della tesi e' l'approfondimento su tecniche e metodiche di preservazione del polmone isolato per lo studio ecografico. E' discussa l'appropriatezza sull'uso degli ultrasuoni in corso di chirurgia mini invasiva polmonare, obiettivo di una ricerca sperimentale. Il razionale dello studio si fonda sull'indicazione all'exeresi chirurgica di noduli polmonari di diametro inferiore al centometro, ovvero di diametro superiore ma localizzati in aree centrali del polmone. Queste lesioni sono sempre piu' frequentente diagnosticate per mezzo di avanzate tecniche di imaging. L'atto chirurgico ha scopo terapeutico quando sia stata posta la diagnosi di neoplasia maligna, diagnostico-terapeutico quando non sia ancora ottenuta la tipizzazione istologica della lesione. La tecnica toracoscopica offre numerosi vantaggi rispetto alle tecniche chirurgiche tradizionali ma presenta il grave limite di non permettere la palpazione diretta del tessuto polmonare e la localizzazione della formazione tumorale quando essa non sia visibile macroscopicamente. Gli ultrasuoni sono stati utilizzati con successo per indirizzare la localizzazione del nodulo polmonare. Scopo dello studio sperimentale e' quello di confrontare tecniche diverse di preservazione del polmone isolato in un modello animale, comparando catatteristiche e prestazioni di sonde ecografiche differenti per tipologia. Del tutto recentemente, in ambito trapiantologico, sono state proposte tecniche di preservazione organica utili ai fini di uno studio anatomico sperimentale particolareggiato (EVLP) e moderna e' da considerarsi la concezione di mezzi tecnici specifici per la localizzazione di bersagli intrapolmonari. La tecnica clinica applicata allo studio del particolare ecografico, nel modello animale, ha reso comprensibile e meglio definito il ruolo delle sonde ecografiche nell'individuazione di forme tumorali suscettibili di exeresi definitiva.