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.

Incidence of neoplastic disease following lung transplantation: a 17-year single-center experience.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Preemptive therapy for systemic and pulmonary human cytomegalovirus infection in lung transplant recipients.

The incidence and treatment of both systemic and pulmonary human cytomegalovirus (HCMV) infection as well as HCMV-specific T-cell immune responses were investigated in 57 consecutive lung transplant recipients (LTR) by using as cutoffs for preemptive therapy: 300 000 DNA copies/mL whole blood for systemic infections and 100 000 DNA copies/mL bronchoalveolar lavage fluid for lung infections. Results showed that out of 29/57 LTR (50.9%) needing preemptive antiviral therapy, 15 (51.7%) reached the blood cutoff, 8 (27.6%) the pulmonary cutoff and 6 (20.7%) both the blood and the lung cutoff (3 simultaneously and 3 subsequently). Recovery of HCMV-specific T-cell immune responses was achieved much earlier for CD8+ than CD4+ T cells. However, protection from HCMV reactivation was conferred by the presence of both arms of the T-cell response. In two LTR reaching the pulmonary cutoff and not preemptively treated, a full HCMV-specific CD4+ and CD8+ T-cell response was associated with resolution of lung infection. Antirejection steroid therapy suppressed T-cell immune responses, thus facilitating HCMV reactivation. In conclusion, in LTR, monitoring HCMV infection in both blood and lungs, may improve preemptive therapy efficacy. In addition, monitoring the HCMV-specific T-cell immune response appears useful for predicting control of HCMV infection in the posttransplant period.

Determinants of quality of life after lung transplant: an Italian collaborative study.

BACKGROUND: With the improvement in survival rates after lung transplantation, concern has arisen about evaluating quality of life (QoL). This multicenter cross-sectional study aimed at describing QoL and identifying factors associated with it. METHODS: We assessed QoL in 129 lung transplant recipients from 5 centres in Italy, during scheduled follow-up visits, using the SF-36, GHQ and St George's respiratory questionnaires (SGRQ). RESULTS: The SF-36 elicited impaired QoL in the physical, but not in the mental domains (PCS = 44; MCS = 53). The GHQ identified 29 patients (23%) with psychological discomfort and the SGRQ scores were significantly better than those of patients with chronic respiratory disease. On multivariate analysis, exertional dyspnea was an independent predictor of the PCS (adjusted delta -6.3 (p < 0.001), while osteoporosis (delta = -3.1), BOS (delta = -4.3), acute rejection (delta = -3.9) and heart and lung transplant (delta = +6.4) were only marginally associated. Dyspnea was also related to a GHQ score > 5. CONCLUSIONS: The study identified exertional dyspnea as the main determinant of QoL as measured both by SF36 (PCS) and GHQ. Other objective measures contributed only to the PCS. Thus, the SF-36 (PCS) and GHQ were useful in identifying patients who needed treatment not only for complications but also psychological support and continued physical rehabilitation.

Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis.

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 BAL cells, with a peak at day 7. TIMP-1 and TIMP-2 concentration (ELISA) enhancement was delayed at day 14. In conclusion gelatinases and their inhibitors are significantly activated during bleomycin-induced pulmonary fibrosis. Marked changes in gelatinases activity are observed early in the alveolar compartment, with a prevailing extracellular activity of MMP-2 and a predominant intracellular distribution of MMP-9, while enzyme activity changes in lung parenchyma were less evident. In the repairing phase the reduction of gelatinases activity is synchronous with a peak of alveolar concentration of their inhibitors.

Lymphocyte expression of human leukocyte antigen class II molecules in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a multifactorial disorder, deriving from a combination of environmental and genetic factors. Polymorphisms of genes of the human major histocompatibility complex in COPD have been poorly studied in the past. In a preliminary approach, it was difficult to type human leukocyte antigen (HLA) at the protein level and it was hypothesized that there was a reduced surface density of HLA class II molecules. The aims of this study were to analyse, by cytofluorimetry, HLA class I and II molecule densities on peripheral mononuclear cells of COPD patients and to investigate whether there was a correlation with the polymorphisms of DQA and DQB promoter regions which are supposed to be important factors involved in surface expression of HLA-DQ molecules. The study investigated 27 male COPD patients admitted because of disease exacerbation and 49 healthy male controls. Quantitative analysis of fluorescence intensity of HLA class I (A, B, C) and class II (DR, DP, DQ) molecules was performed on blood mononuclear cells by cytoron cytofluorimetry. Polymorphisms of DQA and DQB promoters (QAP and QBP) were determined from the DNA (PCR-SSO). The surface densities of HLA class I and HLA-DQ molecules did not differ between the COPD patients and controls. HLA-DP molecule density seemed to be slightly, but not significantly lower in COPD, whereas surface HLA-DR molecules were significantly reduced (p < 0.005 vs controls). Frequencies of QAP alleles were not different between the COPD patients and controls, but the QBP 5.12 allele was significantly more frequent in COPD than in controls (chi 2 = 10.83, p = 0.0182, RR 5.5). In conclusion, individuals with exacerbated chronic obstructive pulmonary disease have reduced surface DR molecule expression and an increased frequency of the QBP 5.12 allele. The possible relationship between these two features and the possible role of cytokines in reducing human leukocyte antigen-DR expression in exacerbated chronic obstructive pulmonary disease is explored.

Respiratory bronchiolitis-associated interstitial lung disease: a case report with bronchoalveolar lavage findings.

We report a case of respiratory bronchiolitis-associated interstitial lung disease in a young asymptomatic heavy cigarette smoker. Diagnosis was achieved by examination of specimens obtained from open lung biopsy, but retrospective evaluation of bronchoalveolar lavage findings offer some circumstantial suggestions. We provide evidence for the nature of inclusions contained in alveolar macrophages. Problems related to the classification of respiratory bronchiolitis-associated interstitial lung disease are also discussed.