Selection of Candidates for Lung Transplantation: The First Italian Consensus Statement

Lung transplantation is a well-established treatment for selected patients with advanced chronic respiratory insufficiency. Recognizing those patients with end-stage lung disease who might benefit from lung transplantation is a crucial task. Considering the presence of inadequate evidence-based practice, international and national scientific societies provided consensus opinions regarding the appropriate timing of listing. The Study Group for Thoracic Organs Transplantation (branch of the Italian Society for Organs Transplantation) promoted and realized a Delphi conference among the Italian lung transplantation centers to provide guidance to clinical practice based on international recommendations. The experts from the nine Italian centers completed two rounds of standardized questionnaires (answer rate, 100%): 42 statements received a consensus >= 80%. The selected statements presented in this article are intended to assist Italian clinicians in selecting patients for lung transplantation

A valid academic path to promote respiratory physiotherapy

A one- year post- graduate Master in Physiotherapy and Pulmonary Rehabilitation has been offered within the University of Milan Medical School in collaboration with Associaz ione Italiana Riabilitatori dell\u2019Insufficienz a Respiratoria (ARIR). The aim is to cover a gap in Italian Physiotherapy academic curricula offering a course with theoretical and practical teaching that make students capable of using different techniques and procedures in respiratory physiotherapy. After the recognition by the International Education Recognition System (IERS), ARIR wanted to investigate if and how this course has affected students'attitude and their profession. METHODS A structured questionnaire made up of 15 multiple- choices items (8 on perceived quality of education and 7 on professional change) was sent by email to all physiotherapists who graduated in the previous four editions of the Master. One month was given for completion. Age, gender, year of degree and year of Master where considered as background variables. RESULTS We had a 78% response rate with 57 out of 73 physiotherapists sending the questionnaire back. Mean age was 37 years (23- 60) and women were the majority (78%). Forty- two students (74%) worked in the respiratory field at the time of application but only 15 (36%) dealt with respiratory patients only. Expectations were completely met at the end of Master for 71% of physiotherapists. 96% reported greater professional and clinical skills after the master with a 67% saying working team relationship has improved. 28% improved their job position thanks to the master degree and physiotherapy working in the respiratory field increased by 22%. CONCLUSIONS This course seems to meet students expectations and offer a solid knowledge to better work within the field of respiratory physiotherapy. It is also a way to promote the profession of respiratory physiotherapy in Italy

Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome after Lung Transplantation

Background. Primary graft dysfunction, infections, and acute rejection (AR) worsen lung transplantation (LTx) outcome and patient survival. Despite significant efforts, reliable biomarkers of acute lung allograft dysfunction are lacking. To address this issue, we profiled the bronchoalveolar lavage (BAL) miRNome in LTx patients. Methods. BAL-microRNAs (miRNAs) from 16 patients were collected 7 days (T0), 15 days (T1), and 3 months (T2) after bilateral LTx and profiled on low-density array. Unsupervised and supervised analyses were used to identify miRNAs associated with clinical features, pneumonia, or AR. Prognostic markers were identified using the Cox model. Targeted signaling pathways were predicted in silico. A second series of 11 patients were used to validate AR-associated miRNAs. Results. Variation in BAL-miRNAs was associated with acute lung allograft dysfunction. Increased levels of miR-23b-3p at T2 were detected in patients with pneumonia, whereas let-7f-5p, miR-146b-3p, miR-22-5p, miR-29c-5p, miR-362-5p, and miR-452-5p were upregulated at T2 in patients with AR. miR-148b-5p and miR-744-3p distinguished LTx patients with AR in both cohorts. Low miR-148b-5p and high miR-744-3p expression levels were significantly associated with a shorter time to AR either within the first year after LTx or during follow-up. Combination of the 2 miRNAs identified LTx patients with higher AR risk independently of clinical variables. Conclusions. Our data provide new insights into the roles of BAL-miRNAs in regulating the pulmonary environment after transplantation and suggest that these miRNAs could serve as biomarkers of early- or mid-stage events. If validated, these findings could pave the way to a personalized clinical approach in LTx patients

Pulmonary adenocarcinoma with massive lymphocytic infiltration: a case report with review of the literature of a rare histological entity with a peculiar biological behaviour

BACKGROUND: Tumors with a massive inflammatory infiltration are described in several organs. There is agreement about considering the inflammatory infiltration as the host's immune response to neoplastic cells; such neoplasms indeed have a better prognostic outcome than non-inflammatory counterparts. Only seventeen cases of pulmonary adenocarcinoma with massive lymphocytic infiltration (AMLI) have been reported in literature so far. CASE PRESENTATION: We present a case of pulmonary adenocarcinoma with massive lymphocytic infiltration occurring in a 71 years old male smoker. He came under our attention because of dyspnea, and underwent a left lower lobectomy. Histological examination showed a moderately differentiated (G2) acinar adenocarcinoma associated with a stromal desmoplastic reaction and a massive inflammatory infiltration, made up mostly of CD3+ lymphocytes. pTNM stage was pT2a, N0 (clinical stage: Ib).Molecular testing of EGFR gene showed no mutations and immunohistochemistry for ALK resulted negative.EBV infection was ruled out by EBV in situ hybridization. CONCLUSIONS: Literature review showed seventeen similar cases, with a 16/1 male/female ratio and a mean age of 70,2 years. In eight out of seventeen cases EBV-infection was demonstrated with immunohistochemical or molecular biology techniques.Similarly to the cases previously reported in literature our patient is a male smoker, without lymph node metastasis and he is still alive after a follow-up period of six months without recurrent or residual disease.Because of histological, biological and clinical peculiarity, we propose to take into account pulmonary adenocarcinomas with massive inflammatory infiltration for a separate pathological classificatio

Sympatho-Vagal Dysfunction in Patients with End-Stage Lung Disease Awaiting Lung Transplantation

Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 \ub1 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 \ub1 16 years) were enrolled in a case-control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients

Allocazione tramite lung allocation score, prima esperienza italiana

Pur in assenza di un\u2019evidenza statistica si nota una tendenza favorevole all\u2019applicazione del LAS in termini di ridotta mortalit\ue0 in lista e diminuita attesa al trapianto. Tale tendenza pu\uf2 essere considerata un valido supporto alla prosecuzione dell\u2019allocazione tramite LAS per almeno un altro anno al fine di confermare tali dati e analizzare l\u2019effetto sull\u2019outcome ad un anno. Introduzione: Nel Maggio 2005, un innovativo algoritmo di allocazione denominato Lung Allocation Score (LAS) fu introdotto negli Stati Uniti dall\u2019organizazione United Network for Organ Sharing per determinare la priorit\ue0 di allocazione degli organi ai pazienti in lista d\u2019attesa. Introdotto anche in alcuni Paesi europei, il LAS \ue8 stato utilizzato come sistema di allocazione in una regione italiana dal Marzo 2016. Il presente studio intende esaminare i primi risultati ottenuti con questo sistema di allocazione ad un anno dalla sua introduzione. Metodologia: Tutti I pazienti trapiantati nella regione interessata tra l\u20191/1/2011 e il 31/3/2017 sono stati inseriti nello studio. Le procedure eseguite dopo l\u2019introduzione del LAS sono state confrontate con le precedenti. I dati clinici e demografici sono stati estratti dai sistemi informativi nazionali. Risultati: Il controllo storico contava 415 pazienti in lista d\u2019attesa con 91 decessi per una mortalit\ue0 media annuale del 13,7%; i pazienti in lista nell\u2019anno d\u2019applicazione del LAS erano 134 con 10 decessi ed una mortalit\ue0 del 7.5% (p=0.1). Durante il periodo storico i 199 pazienti trapiantati hanno avuto un\u2019attesa media di 11,84 mesi mentre nel \u201cperiodo LAS\u201d i 51 pazienti trapiantato hanno avuto un\u2019attesa di 9.98 mesi (p=0.9). Conclusioni: Pur in assenza di un\u2019evidenza statistica si nota una tendenza favorevole all\u2019applicazione del LAS in termini di ridotta mortalit\ue0 in lista e diminuita attesa al trapianto. Tale tendenza pu\uf2 essere considerata un valido supporto alla prosecuzione dell\u2019allocazione tramite LAS per almeno un altro anno al fine di confermare tali dati e analizzare l\u2019effetto sull\u2019outcome ad un anno

Pleural tissue repair with cord blood platelet gel

BACKGROUND: Prolonged air leak is the major cause of morbidity after pulmonary resection. In this study we used in vitro and in vivo experiments to investigate an innovative approach based on the use of human umbilical cord blood platelet gel. MATERIALS AND METHODS: In vitro, a scratch assay was performed to test the tissue repair capability mediated by cord blood platelet gel compared to the standard culture conditions using human primary mesothelial cells. In vivo, an iatrogenic injury was made to the left lung of 54 Wistar rats. Cord blood platelet gel was placed on the injured area only in treated animals and at different times histological changes and the presence of pleural adhesions were evaluated. In addition, changes in the pattern of soluble inflammatory factors were investigated using a multiplex proteome array. RESULTS: In vitro, mesothelial cell damage was repaired in a shorter time by cord blood platelet gel than in the control condition (24 versus 35 hours, respectively). In vivo, formation of new mesothelial tissue and complete tissue recovery were observed at 45\ub11 and 75\ub11 hours in treated animals and at 130\ub12.5 and 160\ub16 hours in controls, respectively. Pleural adhesions were evident in 43% of treated animals compared to 17% of controls. No complications were observed. Interestingly, some crucial soluble factors involved in inflammation were significantly reduced in treated animals. DISCUSSION: Cord blood platelet gel accelerates the repair of pleural damage and stimulates the development of pleural adhesions. Both properties could be particularly useful in the management of prolonged air leak, and to reduce inflammatio

Non-invasive continuous positive airway pressure in monolateral lung transplant patient with pneumonia and IPF

Patients who undergo lung transplantation are prone to develop lower respiratory tract infections, leading to severe acute respiratory failure (ARF). Endotracheal intubation may not be indicated in these patients in light of a higher rate of mortality due to infections. The application of non-invasive ventilation could play a role in bridging these patients through the episode of ARF waiting for medical treatment to have effect. We report the evidence of morphological and physiological effects of the application of non-invasive continuous positive airway pressure during ARF sustained by pneumonia in a patient who underwent left lung transplantation because of idiopathic pulmonary fibrosis (IPF). We studied the effects of the application of positive end-expiratory pressure on both the right native lung affected by IPF and the transplanted lung affected by pneumonia

Non-invasive continuous positive airway pressure in monolateral lung transplant patient with pneumonia and IPF

Patients who undergo lung transplantation are prone to develop lower respiratory tract infections, leading to severe acute respiratory failure (ARF). Endotracheal intubation may not be indicated in these patients in light of a higher rate of mortality due to infections. The application of non-invasive ventilation could play a role in bridging these patients through the episode of ARF waiting for medical treatment to have effect. We report the evidence of morphological and physiological effects of the application of non-invasive continuous positive airway pressure during ARF sustained by pneumonia in a patient who underwent left lung transplantation because of idiopathic pulmonary fibrosis (IPF). We studied the effects of the application of positive end-expiratory pressure on both the right native lung affected by IPF and the transplanted lung affected by pneumonia

Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant : An Italian Multicenter Experience

Background and aim: Liver transplantation (LT) is a validated treatment for hepatocellular carcinoma (HCC). HCC recurrence occurred between 8 and 20% of patients and lung is the most frequent site. Pulmonary metastases resection (PMR) prolongs survival, however in LT-setting the impact on survival is unclear. To give new lights on this issue, we report the experience of three Italian LT Centers. Methods: All consecutive HCC transplanted patients in three Italian LT Centers, who developed pulmonary metastasis from HCC (PM-HCC), as first metastasis, from 2008 to 2018, were included whenever treated with PMR. Results: Twenty-five patients were enrolled (median age 58 yrs, 84% male, 3% cirrhotics). HCC recurred after 34 months (9\u2013306) since LT and PMR was performed after 2.4 months (0\u201343.1). A total of 28 PMR (19 single resections; 9 multiple resections; 16 right; 2 left) have been performed on 24 patients while in one case percutaneous microwave ablation (MWA) was preferred. Four patients have been re-operated due to pulmonary HCC-recurrence after surgery. The majority of surgical resection type was wedge resection (26, 89%). Surgical access was: video-assisted thoracic surgery (VATS) in 17 cases (59%); thoracotomy in 11 (38%); MWA in 1 (3%). The 48% of nodule was in right lower lobe. Perioperative in-hospital mortality and 30 days mortality were nil; median surgical time 90 min (50\u2013365); median post-operative overall stay 5 days (2\u201311). Post-operative ICU treatment was necessary in 1 case (3%) for 3 days; blood transfusions in 2 cases (7%). Overall, 5 complications (2 bleeding; 1 AKI; 1 major cardiac; 1 wound dehiscence) occurred, with an overall complications rate of 23%. Eight (32%) patients died during a follow-up after HCC recurrence of 32 months (7\u2013213): 7 for HCC progression, 1 for severe liver failure due to chronic rejection. The 1 and 5 year cumulative probability of OS from recurrence were 100 and 43% (95%CI 12\u201374), respectively, with a median OS of 51 months (95%CI 24\u201378). Conclusion: Selected patients with isolated pulmonary HCC-recurrence after LT and with preserved hepatic function showed that a pulmonary metastasectomy could be efficacious in managing a PM-HCC and could give an opportunity for long-term survival