Ostéo-arthropathie hypertrophiante révélatrice d'un hémangio-endothéliome épithélioïde multifocal hépatique et pulmonaire [Hypertrophic osteoarthropathy disclosing hepatic and pulmonary multifocal epithelioid hemangioendothelioma]

Epithelioid hemangioendothelioma is a rare, low-grade vascular malignancy reported for the first time in 1982 by Weiss and Enzinger. It involves one or, more rarely, several organs. We report a case involving the lungs and liver, in which the first manifestation was symptomatic hypertrophic osteoarthropathy. Findings four years after the diagnosis included very slow tumor spread, resolution of symptoms, and stabilization of radiological changes.

Lung microbiota promotes tolerance to allergens in neonates via PD-L1.

Epidemiological data point toward a critical period in early life during which environmental cues can set an individual on a trajectory toward respiratory health or disease. The neonatal immune system matures during this period, although little is known about the signals that lead to its maturation. Here we report that the formation of the lung microbiota is a key parameter in this process. Immediately following birth, neonatal mice were prone to develop exaggerated airway eosinophilia, release type 2 helper T cell cytokines and exhibit airway hyper-responsiveness following exposure to house dust mite allergens, even though their lungs harbored high numbers of natural CD4(+)Foxp3(+)CD25(+)Helios(+) regulatory T (Treg) cells. During the first 2 weeks after birth, the bacterial load in the lungs increased, and representation of the bacterial phyla shifts from a predominance of Gammaproteobacteria and Firmicutes towards Bacteroidetes. The changes in the microbiota were associated with decreased aeroallergen responsiveness and the emergence of a Helios(-) Treg cell subset that required interaction with programmed death ligand 1 (PD-L1) for development. Absence of microbial colonization(10) or blockade of PD-L1 during the first 2 weeks postpartum maintained exaggerated responsiveness to allergens through to adulthood. Adoptive transfer of Treg cells from adult mice to neonates before aeroallergen exposure ameliorated disease. Thus, formation of the airway microbiota induces regulatory cells early in life, which, when dysregulated, can lead to sustained susceptibility to allergic airway inflammation in adulthood.

Characterization of the enzyme involved in the processing of big endothelin-1 in human lung epithelial cells.

Biosynthesis of active endothelin-1 (ET-1) implies an enzymatic processing of the inactive precursor Big ET-1 (1-39) into the mature, 21 amino acid peptide. The aim of this study was to characterize in airway and alveolar epithelial cells the enzymes responsible for this activation. BEAS-2B and A549 cells, which both produce ET-1, were studied in vitro as models for bronchiolar and alveolar cells, respectively. Both cell lines were able to convert exogenously added Big ET-1 (0.1 microM) into ET-1, suggesting a cell surface or an extracellular processing. The conversion was inhibited by phosphoramidon in both cell lines with an IC50 approximately 1 microM, but not by thiorphan, a specific inhibitor of neutral endopeptidase 24.11 (NEP). The endogenous production of serum-stimulated BEAS-2B and A549 cells was not inhibited by thiorphan, and phosphoramidon showed inhibition only at high concentration (>100 microM). Western blotting following electrophoresis in reducing conditions demonstrated a protein of MR 110 corresponding to the ECE-1 monomer in both BEAS-2B and A549 cells, as well as in whole lung extracts. By RT-PCR we revealed the mRNA encoding for the ECE-1b and/or -1c subtype, but not ECE-1a, in both cell lines. We conclude that BEAS-2B and A549 cells are able to process either endogenous or exogenous Big ET-1 by ECE-1 and that isoforms 1b and 1c could be involved in this processing with no significant role of NEP.

Mycosis fungoides in a lung transplant recipient with advanced ciclosporin nephropathy: management with mechlorethamine and subsequent renal transplantation.

Posttransplant cutaneous T cell lymphomas are rare and have been reported to have a poor prognosis. We report the case of a follicular mycosis fungoides in a lung transplant recipient who was successfully treated with topical mechlorethamine, prior to subsequent renal transplantation.

Toxic effects of brake wear particles on epithelial lung cells in vitro

Background: Fine particulate matter originating from traffic correlates with increased morbidity and mortality. An important source of traffic particles is brake wear of cars which contributes up to 20% of the total traffic emissions. The aim of this study was to evaluate potential toxicological effects of human epithelial lung cells exposed to freshly generated brake wear particles. Results: An exposure box was mounted around a car's braking system. Lung cells cultured at the air-liquid interface were then exposed to particles emitted from two typical braking behaviours ("full stop" and "normal deceleration"). The particle size distribution as well as the brake emission components like metals and carbons was measured on-line, and the particles deposited on grids for transmission electron microscopy were counted. The tight junction arrangement was observed by laser scanning microscopy. Cellular responses were assessed by measurement of lactate dehydrogenase (cytotoxicity), by investigating the production of reactive oxidative species and the release of the pro-inflammatory mediator interleukin-8. The tight junction protein occludin density decreased significantly (p < 0.05) with increasing concentrations of metals on the particles (iron, copper and manganese, which were all strongly correlated with each other). Occludin was also negatively correlated with the intensity of reactive oxidative species. The concentrations of interleukin-8 were significantly correlated with increasing organic carbon concentrations. No correlation was observed between occludin and interleukin-8, nor between reactive oxidative species and interleukin-8. Conclusion: These findings suggest that the metals on brake wear particles damage tight junctions with a mechanism involving oxidative stress. Brake wear particles also increase pro-inflammatory responses. However, this might be due to another mechanism than via oxidative stress. [Authors]

Hochkalorische Ernährung bei chronischer obstruktiver Lungenkrankheit [High-caloric nutrition in chronic obstructive lung disease]

A body weight lower than 90% of the optional value has an unfavorable influence on the prognosis of chronic obstructive pulmonary disease (COPD). Short term studies of up to three months duration have shown improved function of respiratory muscle exercise tolerance and immunologic parameters by an increased caloric intake of 45 kcal/kg body weight. In a randomized trial of twelve months 14 of 30 patients with an average FEV1 of 0.8 l were instructed to take a high calorie diet. For simplicity a part of the calories were administered as Fresubin, a fluid nutrient formula. Although a weight gain of 7 kg (p = 0.003) was obtained the difference to the control group was statistically not significant (p = 0.08). The same was true for skin fold thickness (12.4 vs 5.7 mm), change of ventilatory parameters and the 6 minute walking distance (-33 vs -86 m). Subjective improvement was, however, impressive in all patients with dietary intervention, explainable probably by increased attention. Dietary counselling for increased intake of calories, vitamins and also calcium is thus very important in the treatment of patients with COPD.

Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre.

BACKGROUND: Uveal metastasis is the most common intraocular malignancy. METHODS: This was a retrospective study of all patients with uveal metastases referred to the Liverpool Ocular Oncology Centre between January 2007 and December 2012. Biopsy was performed as a primary investigation if the clinical examination suggested metastasis with no evidence of any extraocular metastases. RESULTS: Ninety-six patients (109 eyes) were included. Breast and lung carcinomas were the most common primary malignancies, affecting 41 and 27 patients, respectively. The median time interval between detection of primary cancer and uveal metastasis was 24 months (range 1-288 months). Thirty-nine patients underwent ocular biopsy, confirming the diagnosis in all patients. The biopsy indicated the site of origin in 24 out of the 27 without a known primary tumour. In 7 of these 27 cases, previous systemic investigations had failed to identify the primary tumour. Seventy-three patients received external beam irradiation; two patients received photodynamic therapy; and two patients had Ru-106 plaque radiotherapy. The visual acuity was stable or improved in 75.5% of the cases. CONCLUSIONS: Immediate biopsy provides a quick diagnosis that may expedite treatment and improve any opportunities for conserving vision while facilitating the general oncologic management on these patients.

Transcatheter aortic valve implantation in a lung transplant recipient.

Transcatheter aortic valve implantation is a feasible therapeutic option for selected patients with severe aortic stenosis and high or prohibitive risk for standard surgery. Lung transplant recipients are often considered high-risk patients for heart surgery because of their specific transplant-associated characteristics and comorbidities. We report a case of successful transfemoral transcatheter aortic valve replacement in a lung transplant recipient with a symptomatic severe aortic stenosis, severe left ventricular dysfunction, and end-stage renal failure 9 years after bilateral lung transplantation.

A Randomized Controlled Trial Comparing Intradermal vs. Intramuscular Influenza Vaccine in Lung Transplant Recipients

Background: Immunogenicity of standard infl uenza vaccine is suboptimal in lung transplant recipients. Intradermal vaccine may elicit stronger responses due to recruitment of local dendritic cells. We compared the immunogenicity of the infl uenza vaccine administered intradermally (ID) to the standard intramuscular (IM) vaccination. Methods: In this investigator-blinded, two-center, prospective trial, lung transplant patients were randomized to receive intradermal (6ug) or intramuscular (15ug) 2008/9 trivalent inactivated infl uenza vaccine. Immunogenicity was evaluated using a standard hemagglutination inhibition assay (HIA). Response to the vaccine was defi ned as a fourfold increase of the HIA levels for any of the 3 viral strains in the vaccine. Geometric mean titers (GMT) and seroprotection rate (HIA ≥32) were also analyzed. Patients were followed during 6 months for the development of infl uenza or acute rejection. Results: We randomized 84 patients to receive the ID (n=41) vs. IM (n=43) vaccine, respectively. Baseline characteristics were similar between groups. Median time from transplantation was 3.4 yrs (ID) vs. 3.3 yrs (IM) (p=0.84). Vaccine response to at least one antigen was seen in 6/41 (14.6%) patients in the ID vs. 8/43 (18.6%) in the IM group (p=0.77). In the ID group, GMTs (95% CI) after vaccination were 15.7 (11.1-22.3) for H1N1, 84.0 (52.0-135.7) for H3N2, and 14.5 (9.6-21.8) for B strains vs. in the IM group 17.5 (11.8-25.9) for H1N1, 108.9 (77.5-153.2) for H3N2, and 20.2 (12.8-31.9) for B (p=NS, all 3 strains). Seroprotection was 39% (H1N1), 82.9% (H3N2) and 29.3% (B strain) in the ID group vs. 27.9% (H1N1), 97.7% (H3N2) and 58.1% (B strain) in the IM group. No factors associated with vaccine response were identifi ed. Mild adverse events were seen in 44% of patients (ID) vs. 34% (IM) (p=0.38). Two patients (4.8%) in the ID group developed infl uenza infection compared to none in the IM group. Two patients in each group developed biopsy-proven acute rejection during follow-up. Conclusions: Immunogenicity of the 2008/09 infl uenza vaccine was poor in lung transplant recipients. ID administration of the vaccine elicited similar immune responses to standard IM vaccination. Novel strategies of vaccination are needed to protect lung transplant recipients from infl uenza.

Risk factors for survival after lung metastasectomy in colorectal cancer patients: a systematic review and meta-analysis.

BACKGROUND: Resection of lung metastases (LM) from colorectal cancer (CRC) is increasingly performed with a curative intent. It is currently not possible to identify those CRC patients who may benefit the most from this surgical strategy. The aim of this study was to perform a systematic review of risk factors for survival after lung metastasectomy for CRC. METHODS: We performed a meta-analysis of series published between 2000 and 2011, which focused on surgical management of LM from CRC and included more than 40 patients each. Pooled hazard ratios (HR) were calculated by using random effects model for parameters considered as potential prognostic factors. RESULTS: Twenty-five studies including a total of 2925 patients were considered in this analysis. Four parameters were associated with poor survival: (1) a short disease-free interval between primary tumor resection and development of LM (HR 1.59, 95 % confidence interval [CI] 1.27-1.98); (2) multiple LM (HR 2.04, 95 % CI 1.72-2.41); (3) positive hilar and/or mediastinal lymph nodes (HR 1.65, 95 % CI 1.35-2.02); and (4) elevated prethoracotomy carcinoembryonic antigen (HR 1.91, 95 % CI 1.57-2.32). By comparison, a history of resected liver metastases (HR 1.22, 95 % CI 0.91-1.64) did not achieve statistical significance. CONCLUSIONS: Clinical variables associated with prolonged survival after surgery for LM in CRC patients include prolonged disease-free interval between primary tumor and metastatic spread, normal prethoracotomy carcinoembryonic antigen, absence of thoracic node involvement, and a single pulmonary lesion.

Impact of bedside open lung biopsies on the management of mechanically ventilated immunocompromised patients with acute respiratory distress syndrome of unknown etiology.

BACKGROUND: Open lung biopsy (OLB) is helpful in the management of patients with acute respiratory distress syndrome (ARDS) of unknown etiology. We determine the impact of surgical lung biopsies performed at the bedside on the management of patients with ARDS. METHODS: We reviewed all consecutive cases of patients with ARDS who underwent a surgical OLB at the bedside in a medical intensive care unit between 1993 and 2005. RESULTS: Biopsies were performed in 19 patients mechanically ventilated for ARDS of unknown etiology despite extensive diagnostic process and empirical therapeutic trials. Among them, 17 (89%) were immunocompromised and 10 patients experienced hematological malignancies. Surgical biopsies were obtained after a median (25%-75%) mechanical ventilation of 5 (2-11) days; mean (+/-SD) Pao(2)/Fio(2) ratio was 119.3 (+/-34.2) mm Hg. Histologic diagnoses were obtained in all cases and were specific in 13 patients (68%), including 9 (47%) not previously suspected. Immediate complications (26%) were local (pneumothorax, minimal bleeding) without general or respiratory consequences. The biopsy resulted in major changes in management in 17 patients (89%). It contributed to a decision to limit care in 12 of 17 patients who died. CONCLUSION: Our data confirm that surgical OLB may have an important impact on the management of patients with ARDS of unknown etiology after extensive diagnostic process. The procedure can be performed at the bedside, is safe, and has a high diagnostic yield leading to major changes in management, including withdrawal of vital support, in the majority of patients.

Lung cancer in the Swiss HIV Cohort Study: role of smoking, immunodeficiency and pulmonary infection.

BACKGROUND: Immunodeficiency and AIDS-related pulmonary infections have been suggested as independent causes of lung cancer among HIV-infected persons, in addition to smoking. METHODS: A total of 68 lung cancers were identified in the Swiss HIV Cohort Study (SHCS) or through linkage with Swiss Cancer Registries (1985-2010), and were individually matched to 337 controls by centre, gender, HIV-transmission category, age and calendar period. Odds ratios (ORs) were estimated by conditional logistic regression. RESULTS: Overall, 96.2% of lung cancers and 72.9% of controls were ever smokers, confirming the high prevalence of smoking and its strong association with lung cancer (OR for current vs never=14.4, 95% confidence interval (95% CI): 3.36-62.1). No significant associations were observed between CD4+ cell count and lung cancer, neither when measured within 1 year (OR for <200 vs ≥500=1.21, 95% CI: 0.49-2.96) nor further back in time, before lung cancer diagnosis. Combined antiretroviral therapy was not significantly associated with lung cancer (OR for ever vs never=0.67, 95% CI: 0.29-1.52), and nor was a history of AIDS with (OR=0.49, 95% CI: 0.19-1.28) or without (OR=0.53, 95% CI: 0.24-1.18) pulmonary involvement. CONCLUSION: Lung cancer in the SHCS does not seem to be clearly associated with immunodeficiency or AIDS-related pulmonary disease, but seems to be attributable to heavy smoking.

Challenges in lung transplantation.

Lung transplantation is an established therapy for end-stage pulmonary disorders in selected patients without significant comorbidities. The particular constraints associated with organ transplantation from deceased donors involve specific allocation rules in order to optimise the medical efficacy of the procedure. Comparison of different policies adopted by national transplant agencies reveals that an optimal and unique allocation system is an elusive goal, and that practical, geographical and logistic parameters must be taken into account. A solution to attenuate the imbalance between the number of lung transplant candidates and the limited availability of organs is to consider marginal donors. In particular, assessment and restoration of gas exchange capacity ex vivo in explanted lungs is a new and promising approach that some lung transplant programmes have started to apply in clinical practice. Chronic lung allograft dysfunction, and especially bronchiolitis obliterans, remains the major medium- and long-term problem in lung transplantation with a major impact on survival. Although there is to date no cure for established bronchiolitis obliterans, new preventive strategies have the potential to limit the burden of this feared complication. Unfortunately, randomised prospective studies are infrequent in the field of lung transplantation, and data obtained from larger studies involving kidney or liver recipients are not always relevant for this purpose.