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Background: Oxidative stress, resulting from the increased oxidative burden and decreased level of antioxidant proteins, plays a role in the pathophysiology of smoking-related pulmonary emphysema. Expression of several antioxidant proteins, such as heme oxygenase-1 (HO-1), glutathione peroxidase 2 (GPX2) and NAD(P)H:quinone oxidoreductase 1 (NQO1), results from an equilibrium created by positive or negative regulation by the transcription factors Nrf2, Keap1 and Bach1, respectively. However, whether the expression of these transcription factors is altered in emphysema and could account for decreased expression of antioxidant proteins is not known. A study was undertaken to investigate the expression and subcellular localisation of Nrf2, Keap1 and Bach1 as potential regulators of HO-1, GPX2 and NQO1 in alveolar macrophages, a key cell in oxidative stress, in lung surgical specimens from non-smokers without emphysema and smokers with and without emphysema.Methods and Results: Western blot, immunohistochemical and laser scanning confocal analysis revealed that the Nrf2 protein level decreased significantly in whole lung tissue and alveolar macrophages (cytosol and nucleus) in patients with emphysema compared with those without emphysema. Conversely, Bach1 and Keap1 levels were increased in patients with emphysema. These modifications were associated with a parallel decrease in the expression of HO-1, GPX2 and NQO1 at the cellular level, which was inversely correlated with airway obstruction and distension indexes, and increased macrophage expression of the lipid peroxidation product 4-hydroxy-2-nonenal. Silencing RNA experiments in vitro in THP-1 cells were performed to confirm the cause-effect relation between the loss of Nrf2 and the decrease in HO-1, NQO1 and GPX2 expression. Nrf2/Keap1-Bach1 equilibrium was altered in alveolar macrophages in pulmonary emphysema, which points to a decreased stress response phenotype.Conclusions: This finding opens a new view of the pathophysiology of emphysema and could provide the basis for new therapeutic approaches based on preservation and/or restoration of such equilibrium. [ABSTRACT FROM AUTHOR]

Displaced four-part fracture dislocation represents the highest risk of osteonecrosis of the humeral head due to a disruption of the blood supply. In a few cases, that dislocation can be intrathoracic which worsens prognosis with life-threatening injuries such as hemothorax or pneumothorax. This paper presents the case of a 77-year-old woman after having fallen down the stairs with an intrathoracic dislocation four-part fracture leaving the head in the thorax. We analyze mechanisms and review the literature in order to highlight this lesion and provide a take home message for the treatment. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVES: Respiratory complications are frequent after lung transplantation (LTx), and many of these complications have the potential to cause hemoptysis. However, surprisingly, only a few isolated cases of hemoptysis have been reported in LTx recipients. Here, we describe a series of patients who underwent LTx at our center who developed hemoptysis during their postoperative course. SETTING: A tertiary care university hospital. RESULTS: Of 197 LTx recipients, hemoptysis developed in 15 over a 16-year period. The pulmonary circulation as well as the systemic circulation were involved in the mechanism of hemoptysis. Six patients had moderate or minimal hemoptysis, while nine patients had life-threatening hemoptysis, which occurred during the first year after LTx in all cases. Active necrotizing ischemic airway injury was present in five of the nine patients with life-threatening hemoptysis. Eight of those nine patients died as a result of hemoptysis. Overall, hemoptysis was the cause of death in 4.5% of patients who underwent LTx at our institution. CONCLUSION: In our series of transplant patients, hemoptysis was not rare and was associated with a high rate of mortality. [ABSTRACT FROM AUTHOR]

Rationale: The effect of graft ischemic time on early graft function and long-term survival of patients who underwent lung transplantation remains controversial. Consequently, graft ischemic time has not been incorporated in the decision-making process at the time of graft acceptance. Objectives: To investigate the relationship between graft ischemic time and (1) early graft function and (2) long-term survival after lung transplantation. Measurements and main results: The data from 752 patients who underwent single lung transplantation (n = 258), bilateral lung transplantation (n = 247), and heart-lung transplantation (n = 247) in seven French transplantation centers during a 12-year period were reviewed. Independent data quality control was done to ensure the quality of the collected variables. Mean graft ischemic time was 245.8 +/- 96.4 minutes (range 50-660). After adjustment on 11 potential confounders, graft ischemic time was associated with the recipient PaO[2]/FIO[2] ratio recorded within the first 6 hours and with long-term survival in patients undergoing single or double lung transplantation but not in patients undergoing heart-lung transplantation. The relationship between graft ischemic time and survival appears to be of cubic form with a cutoff value of 330 minutes. These results were unaffected by the preservation fluid employed. Conclusions: The results of this large cohort of patients suggest a close relationship between graft ischemic time and both early gas exchange and long-term survival after single and double lung transplantation. Such relationship was not found in patients undergoing heart-lung transplantation. The expected graft ischemic time should be incorporated in the decision-making process at the time of graft acceptance. [ABSTRACT FROM AUTHOR]

Several types of primary disease may recur after lung transplantation, but recurrence of pulmonary emphysema has so far never been published. We report the case of a 49-year-old white male who underwent single lung transplantation for emphysema related to alpha-1 antitrypsin deficiency and to superimposed smoking. The postoperative course was complicated by several rejection episodes. Subsequently, the patient remained stable without evidence of graft dysfunction for more than 10 years, but he resumed light smoking at 8 years after transplant. At 11 years after transplant, although the patient was still asymptomatic and had a stable lung function, recurrence of emphysema on the grafted side was diagnosed on computerized tomography of the thorax. One year later, the patient began to experience a moderate decline in lung function. Two separate bronchoalveolar lavages performed after the onset of the recurrence disclosed a significant elastolytic activity related to neutrophil serine-elastase in lavage fluid. In summary, we describe a case of recurrence of pulmonary emphysema in a patient with alpha-1 antitrypsin deficiency. The resumption of smoking has probably played a central role in the presence of elastolytic activity in lavage fluid and in the recurrence of emphysema. [ABSTRACT FROM AUTHOR]

Guedj N, Couvelard A, Arcangeli G, Dubois S, Thabut G, Lesèche G, Fournier M, Degott C & Groussard O (2004) Histopathology 44, 251–256 Angiogenesis and extracellular matrix remodelling in bronchioloalveolar carcinomas: distinctive patterns in mucinous and non-mucinous tumours Bronchioloalveolar carcinomas (BACs) are rare primitive lung adenocarcinomas growing along the alveolar septum without stromal, vascular or pleural invasion. We report an immunohistochemical study of their vascular microenvironment. In three mucinous BACs (M-BAC) and three non-mucinous BACs (NM-BAC) we examined the following parameters in comparison with the normal lung: (i) constituents of the alveolar extracellular matrix; (ii) qualitative and quantitative changes of alveolar capillaries; and (iii) expression of vascular endothelial growth factor (VEGF) by tumour cells. In M-BAC, the alveolar matrix was unchanged compared with the normal parenchyma. Capillaries expressed normal alveolar endothelial markers and their average surface was calculated, as in normal lung, as 8%. VEGF was negative in tumour cells. In NM-BAC, the alveolar wall was thickened by deposits of fibronectin and type III collagen containing myofibroblasts and the basement membrane was disrupted. Capillaries did not retain alveolar endothelial markers and their surface was calculated as 19%. Tumour cells expressed high levels of VEGF. In contrast to NM-BAC, M-BAC do not modify the alveolar structure and seem to exploit the normal alveolar vascular bed to grow, without inducing neoangiogenesis. A better understanding of the mechanisms of growth of lung cancers may have implications for future anti-angiogenic therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Although lung retransplantation is the only definitive therapeutic option in lung recipients with bronchiolitis obliterans syndrome (BOS), its value remains a considerable source of controversy. We report our experience of retransplantation for BOS performed in our center since 1988.Methods: Between 1988 and 2002, 15 lung retransplantations for BOS were performed. Patient survival, causes of death, long-term functional status, and BOS recurrence rate were reviewed.Results: The retransplantation procedure was single-lung transplantation (SLT) in all cases (ipsilateral SLT, n = 4; contralateral SLT, n = 9; SLT after previous double-lung transplantation, n = 2). The median time between primary lung transplantation and retransplantation was 31 months (range, 12 to 39 months). The median follow-up duration of the 10 patients surviving beyond 6 months was 49.5 months (range, 16.5 to 105 months), and 5 patients were followed up for > 5 years. Actuarial survival rates at 1 year, 2 years, and 5 years after retransplantation were 60%, 53%, and 45%, respectively. Ten patients died during long-term follow-up, 6 of them from infection (60%). The retained graft was the initial site of the fatal infection in four of these six patients (66%). Two other patients with a retained graft experienced disabling chronic purulent expectoration arising from the old graft. In the 10 patients surviving beyond 6 months, mean best FEV(1) was 58 +/- 13% of predicted (+/- SD), and actuarial freedom from BOS (stage 1, 2, or 3) at 1 year, 3 years, and 5 years was 90%, 72%, and 66%, respectively.Conclusion: Lung retransplantation offered a viable therapeutic option for selected lung recipients with BOS. Given the morbidity and mortality related to the retained graft, we now favor replacement of the primary graft when retransplantation is considered. [ABSTRACT FROM AUTHOR]

Study Objectives: To assess incidence, outcome, and early predictors of mortality for patients with primary graft failure (PGF) following lung transplantation (LTx), and to develop an injury severity score able to accurately predict ICU mortality for these patients.Design: Retrospective cohort analysis.Setting: Two LTx centers in Paris.Patients: Two hundred fifty-nine patients who underwent LTx over a 12-year period.Measurements and Results: One hundred thirty-one patients (50.6%) met PGF criteria: radiographic graft infiltrate within the first 3 days following LTx associated with gas exchange impairment (PaO(2)/fraction of inspired oxygen ratio < 300 mm Hg). This syndrome was associated with an increased duration of mechanical ventilation (9.1 +/- 1 days vs 3.1 +/- 0.6 days, mean +/- SD; p < 0.001) and ICU mortality (29% vs 10.9%; p < 0.01). The patients with PGF were randomly assigned to developmental (n = 85) and validation (n = 46) samples. Using logistic regression analysis, four variables were found associated with ICU mortality in these patients: age, degree of gas exchange impairment, graft ischemic time, and severe early hemodynamic failure. An ischemia/reperfusion injury severity score was derived using these four variables. Model calibration was good in the developmental and validation samples, as was model discrimination (area under receiver operating characteristic curves, 0.93 and 0.85, respectively).Conclusion: PGF following LTx is a frequent event, with significant ICU morbidity and mortality. We demonstrate that four simple factors allow prediction of ICU mortality with good accuracy. [ABSTRACT FROM AUTHOR]

Introduction: Among risk factors for the progression of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LT), the influence of time to BOS onset is not known. The aim of the study was to assess if BOS occurring earlier after LT is associated with worse functional prognosis and worse graft survival.Method: We retrospectively compared functional outcome and survival of all single-LT (SLT) recipients who had BOS develop during follow-up in our center according to time to onset of BOS (< 3 years or > or = 3 years after transplantation).Results: Among the 29 SLT recipients with BOS identified during the study period, 20 patients had early-onset BOS and 9 patients had late-onset BOS. The mean decline of FEV(1) over time during the first 9 months in patients with early-onset BOS was significantly greater than in patients with of late-onset BOS (p = 0.04). At last follow-up, patients with early-onset BOS had a lower mean FEV(1) value (25% vs 39% of predicted, p = 0.004), a lower mean PaO(2) value (54 mm Hg vs 73 mm Hg, p = 0.0005), a lower 6-min walk test distance (241 m vs 414 m, p = 0.001), a higher Medical Research Council index value (3.6 vs 1.6, p = 0.0001), and a higher percentage of oxygen dependency (90% vs 11%, p = 0.001) compared with patients with late-onset BOS. In addition, graft survival of patients with early-onset BOS was significantly lower than that of patients with late-onset BOS (log-rank test, p = 0.04). There were 18 of 20 graft failures (90%) in the early-onset BOS group, directly attributable to BOS in all cases (deaths [n = 10] or retransplantation [n = 8]). In the late-onset BOS group, graft failure occurred in four of nine patients due to death from extrapulmonary causes in three of four cases. The median duration of follow-up after occurrence of BOS was not statistically different between patients with early-onset BOS and patients with late-onset BOS (31 +/- 28 months and 37 +/- 26 months, respectively; p = not significant).Conclusion: The subgroup of patients who had BOS develop > or = 3 years after SLT are less likely to have worrisome functional impairment develop in long-term follow-up. Considering the balance between the advantages and risks, enhancement of immunosuppression should be regarded with more caution in this subgroup than in patients with early-onset BOS. [ABSTRACT FROM AUTHOR]