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Les bronchectasies, ou dilatations des bronches, sont des anomalies anatomiques primitives ou secondaires. Leur compréhension est de plus en plus précise grâce à l'augmentation récente du nombre d'études portant sur leur physiopathologie, leur prise en charge et leurs étiologies. À l'heure actuelle, plusieurs pathologies sont associées aux bronchectasies, soit comme une complication de la pathologie initiale, soit à cause de l'existence d'un terrain clinique commun. L'étiologie d'une dilatation des bronches définit sa prise en charge extrarespiratoire, mais aussi le pronostic de l'atteinte pulmonaire et les traitements spécifiques à mettre en place. Il est donc crucial d'adresser un patient porteur de dilatations des bronches à un pneumologue, et de cerner le plus efficacement possible la pathologie causale. Nous établirons succinctement ici l'avancement actuel des connaissances concernant les bronchectasies, leurs étiologies et détaillerons les recommandations en cours pour les explorations initiales. [ABSTRACT FROM AUTHOR]

Background: Airway epithelial cells (AEC) act as the first line of defence in case of lung infections. They constitute a physical barrier against pathogens and they participate in the initiation of the immune response. Yet, the modalities of pathogen recognition by AEC and the consequences on the epithelial barrier remain poorly documented.Method: We investigated the response of primary human AEC to viral (polyinosinic-polycytidylic acid, poly(I:C)) and bacterial (lipopolysaccharide, LPS) stimulations in combination with the lung remodeling factor Transforming Growth Factor-β (TGF-β).Results: We showed a strong production of pro-inflammatory cytokines (Interleukin (IL)-6, Tumor Necrosis Factor α, TNFα) or chemokines (CCL2, CCL3, CCL4, CXCL10, CXCL11) by AEC stimulated with poly(I:C). Cytokine and chemokine production, except CXCL10, was Toll Like Receptor (TLR)-3 dependent and although they express TLR4, we found no cytokine production after LPS stimulation. Poly(I:C), but not LPS, synergised with TGF-β for the production of matrix metalloproteinase-9 (MMP-9) and fibronectin. Mechanistic analyses suggest the secretion of Wnt ligands by AEC along with a degradation of the cellular junctions after poly(I:C) exposure, leading to the release of β-catenin from the cell membrane and stimulation of the Wnt/β-catenin pathway.Conclusion: Our results highlight the cross talk between TGF-β and TLR signaling in bronchial epithelium and its impact on the remodeling process. [ABSTRACT FROM AUTHOR]

Background: Right ventricular function predicts outcome in patients with pulmonary hypertension (PH). Therefore accurate assessment of right ventricular function is essential to graduate severity, assess follow-up, and response to therapy. Purpose: To evaluate whether PH severity could be assessed using electrocardiography-gated CT (ECG-gated CT) functional parameters. A further objective was to evaluate cardiac output (CO) using two ECG-gated CT methods: the reference Simpson technique and the fully automatic technique generated by commercially available cardiac software. Material and Methods: Our institutional review board approved this study; patient consent was not required. Twenty-seven patients who had undergone ECG-gated CT and right heart catheterization (RHC) were included. Two independent observers measured pulmonary artery (PA) diameter, PA distensibility, aorta diameter, right ventricular cardiac output (CT-RVCO) and right ventricular ejection fraction (CT-RVEF) with automatic and Simpson techniques on ECG-gated CT. RHC-CO and mean pulmonary arterial pressure (mPAP) were measured on RHC. Relationship between ECG-gated CT and RHC measurements was tested with linear regression analysis. Results: Inter-observer agreement was good for all measurements (r > 0.7) except for CT-RVCO calculated with Simpson's technique (r = 0.63). Pulmonary artery (PA) distensibility was significantly correlated to mPAP (r = -0.426, P = 0.027). CT-RVEF was correlated with mPAP only when issued from Simpson technique (r = -0.417, P = 0.034). CT-RVEF was not significantly correlated to RHC-CO (P > 0.2). CT-RVCO measured with Simpson technique (r = 0.487, P = 0.010) and automatic segmentation (r = 0.549, P = 0.005) correlated equally with RHC-CO. Conclusion: CT-RVEF and CT-RVCO measured on ECG-gated CT are significantly correlated, respectively, to mPAP and RHC-CO in this population with severe reduction of the right ventricular ejection fraction and could be useful for evaluating and following patients with PH. [ABSTRACT FROM AUTHOR]

Aim: To study the effects of physical training at mild intensities on skeletal muscle energy metabolism in eight patients with chronic obstructive pulmonary disease (COPD) and eight paired healthy sedentary subjects. Methods: Energy metabolism of patients and controls vastus lateralis muscle was studied before and after 3 months of cycling training at mild exercises intensities. Results: The total amount of work accomplished was about 4059 ± 336 kJ in patients with COPD and 7531 ± 1693 kJ in control subjects. This work corresponds to a mechanical power set at 65.2 ± 7.5% of the maximum power for patients with COPD and 52 ± 3.3% of the maximum power in control group. Despite this low level of exercise intensities, we observed an improvement in mitochondrial oxidative phosphorylation through the creatine kinase system revealed by the increased apparent Km for ADP (from 105.5 ± 16.1 to 176.9 ± 26.5 μ m, P < 0.05 in the COPD group and from 126.9 ± 16.8 to 177.7 ± 17.0, P > 0.05 in the control group). Meanwhile, maximal mechanical and metabolic power increased significantly from 83.1 ± 7.1 to 91.3 ± 7.4 Watts ( P < 0.05) and from 16 ± 0.8 to 18.7 ± 0.98 mL O2 kg−1 min−1 ( P < 0.05) only in the COPD group. Conclusion: This study shows that physical training at mild intensity is able to induce comparable changes in skeletal muscles oxidative energy metabolism in patients with COPD and sedentary healthy subjects, but different changes of maximal mechanical and metabolic power. [ABSTRACT FROM AUTHOR]

This paper presents an analysis of the recent tropospheric molecular hydrogen (H2) budget with a particular focus on soil uptake and European surface emissions. A variational inversion scheme is combined with observations from the RAMCES and EUROHYDROS atmospheric networks which include continuous measurements performed between mid-2006 and mid-2009. Net H surface flux, then deposition velocity and surface emissions and finally, deposition velocity, biomass burning, anthropogenic and N2 fixation-related emissions were simultaneously inverted in several scenarios. These scenarios have focused on the sensibility of the soil uptake value to different spatio-temporal distributions. The range of variations of these diverse inversion sets generate an estimate of the uncertainty for each term of the H2 budget. The net H2 flux per region (High Northern Hemisphere, Tropics and High Southern Hemisphere) varies between -8 and +8Tgyr-1. The best inversion in terms of fit to the observations combines updated prior surface emissions and a soil deposition velocity map that is based on bottom-up and top-down estimations. Our estimate of global H2 soil uptake is -59±9 Tg yr -1. Forty per cent of this uptake is located in the High Northern Hemisphere and 55% is located in the Tropics. In terms of surface emissions, seasonality is mainly driven by biomass burning emissions. The inferred European anthropogenic emissions are consistent with independent H2 emissions estimated using a H2/CO mass ratio of 0.034 and CO emissions within the range of their respective uncertainties. Additional constraints, such as isotopic measurements would be needed to infer a more robust partition of H2 sources and sinks. [ABSTRACT FROM AUTHOR]

Background: Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. Objectives: The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. Methods: A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. Results: At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of ­78% and ­57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 ( P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. Conclusions: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma (ClinicalTrials.gov Identifier: NCT00842270). [ABSTRACT FROM AUTHOR]

Rationale: Pulmonary arterial hypertension (PAH) is an orphan disease for which the trend is for management in designated centers with multidisciplinary teams working in a shared-care approach.Objective: To describe clinical and hemodynamic parameters and to provide estimates for the prevalence of patients diagnosed for PAH according to a standardized definition.Methods: The registry was initiated in 17 university hospitals following at least five newly diagnosed patients per year. All consecutive adult ( 18 yr) patients seen between October 2002 and October 2003 were to be included.Main Results: A total of 674 patients (mean +/- SD age, 50 +/- 15 yr; range, 18-85 yr) were entered in the registry. Idiopathic, familial, anorexigen, connective tissue diseases, congenital heart diseases, portal hypertension, and HIV-associated PAH accounted for 39.2, 3.9, 9.5, 15.3, 11.3, 10.4, and 6.2% of the population, respectively. At diagnosis, 75% of patients were in New York Heart Association functional class III or IV. Six-minute walk test was 329 +/- 109 m. Mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance index were 55 +/- 15 mm Hg, 2.5 +/- 0.8 L/min/m[2], and 20.5 +/- 10.2 mm Hg/L/min/m[2], respectively. The low estimates of prevalence and incidence of PAH in France were 15.0 cases/million of adult inhabitants and 2.4 cases/million of adult inhabitants/yr. One-year survival was 88% in the incident cohort.Conclusions: This contemporary registry highlights current practice and shows that PAH is detected late in the course of the disease, with a majority of patients displaying severe functional and hemodynamic compromise. [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]

The objective was to evaluate the helical CT (HCT) criteria that could indicate severe pulmonary embolism (PE). In a retrospective study, 81 patients (mean age 62 years) with clinical suspicion of PE explored by HCT were studied. The patients were separated into three different groups according to clinical severity and treatment decisions: group SPE included patients with severe PE based on clinical data who were treated by fibrinolysis or embolectomy ( n=20); group NSPE included patients with non-severe PE who received heparin ( n=30); and group WPE included patients without PE ( n=31). For each patient we calculated a vascular obstruction index based on the site of obstruction and the degree of occlusion in the pulmonary artery. We noted the HCT signs, i.e., cardiac and pulmonary artery dimensions, that could indicate acute cor pulmonale. According to multivariate analysis, factors significantly correlated with the severity of PE were: the vascular obstruction index (group SPE: 54%; group NSPE: 24%; p<0.001); the maximum minor axis of the left ventricle (group SPE: 30.2 mm; group NSPE: 40.4 mm; p<0.001); the diameter of the central pulmonary artery (group SPE: 32.4 mm; group NSPE: 28.3 mm; p<0.001); the maximum minor axis of the right ventricle (group SPE: 47.5 mm; group NSPE: 42.7 mm; p=0.029); the right ventricle/left ventricle minor axis ratio (group SPE: 1.63; group NSPE: 1.09; p<0.0001). Our data suggest that hemodynamic severity of PE can be assessed on HCT scans by measuring four main criteria: the vascular obstruction index; the minimum diameter of the left ventricle; the RV:LV ratio; and the diameter of the central pulmonary artery. [ABSTRACT FROM AUTHOR]

Summary Background Although allergy is highly associated with childhood asthma, it is not well known if there is a relationship between the intensity of allergic sensitization and asthma severity. Objective The objectives of the study were to examine the relationships between several markers of allergy and asthma severity in asthmatic children included in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy (EGEA). Methods The population comprised 216 asthmatic children below 16 years of age. Total IgE and blood eosinophil counts were measured and skin prick tests to 11 aeroallergens were performed. The intensity of the allergic sensitization was assessed by the number of positive skin prick tests and by skin weal sizes. Asthma severity was measured with four criteria: a clinical severity score, history of hospitalization for asthma, FEV1 % predicted and inhaled steroid use in the last 12 months. Results Most of the children were sensitized to at least one aeroallergen (88.2%). Atopy was not related to the severity of asthma, except for a tendency for a more severe clinical score in non-atopic children. The type and intensity of the allergic sensitization were not associated with any criteria of asthma severity. Total IgE was significantly increased in children treated with inhaled corticosteroids and in children ever hospitalized for asthma (P -values 0.009 and 0.04, respectively). Eosinophil counts were not related to asthma severity. Conclusion Our results suggest that severe childhood asthma may be related to a high level of total IgE but not to blood eosinophil counts. The lack of positive relationships between both atopy and the intensity of allergic sensitization with asthma severity supports the hypothesis of different risk factors being associated with asthma and with the severity of asthma. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare helical CT with fiberoptic bronchoscopy findings to appraise the medium-term results of proximal-airways stenting. Twenty-five patients with 28 endobronchial metallic stents inserted for local advanced malignancy ( n=13) or benign diseases ( n=12) underwent follow-up CT from 3 days to 50 months (mean 8 months). All studies were obtained using helical CT with subsequent multiplanar reformation and three-dimensional reconstruction including virtual bronchoscopy. The location, shape, and patency of stents and adjacent airway were assessed. The results of CT were compared with the results of fiberoptic bronchoscopy obtained with a mean delay of 2.5 days (SD 9 days) after CT scan. Twelve stents (43%) remained in their original position, patent and without deformity. Sixteen stents were associated with local complications: migration ( n=6); external compression with persistent stenosis ( n=4); local recurrence of malignancy ( n=4); fracture ( n=1); and non-congruence between the airway and the stent ( n=1). The CT demonstrated all the significant abnormalities demonstrated at fiberoptic bronchoscopy except two moderate stenoses (20%) related to granulomata at the origin of the stent. Ten of 14 stents inserted for benign conditions were without complications as compared with 2 of 14 in malignant conditions ( p=0.008). Computed tomography is an accurate noninvasive method for evaluating endobronchial stents. The CT is a useful technique for follow-up of patients who have undergone endobronchial stenting. [ABSTRACT FROM AUTHOR]

S. Belaiche, M. Roustit, P. Bedouch, S. Quetant, C. Saint-Raymond, C. Pison. Management of voriconazole hepatotoxicity in a lung transplant patient. Transpl Infect Dis 2011: 309-311. All rights reserved Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We report the case of a 46-year-old female lung transplant outpatient diagnosed with persistent pulmonary Aspergillus colonization (>50 colonies of Aspergillus terreus) 3 months after lung transplantation. Oral voriconazole 200 mg twice a day (b.i.d) was initiated shortly after diagnosis. Two days after voriconazole initiation, alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) were normal or slightly elevated (79, 37, and 21 UI/L, respectively). Ten days after the first voriconazole administration, these values started to increase. Maximum levels were reached after 20 days for ALP (369 UI/L) and at around 30 days for ALT and AST (223 and 188 UI/L, respectively). Instead of discontinuing antifungal therapy, it was decided to reduce the voriconazole dose to 100 mg b.i.d. This asymptomatic progressive cholestatic hepatitis resolved, and 10 days after dose reduction ALP, ALT, AST were at 136, 53, and 28 UI/L, respectively. Finally, therapeutic drug monitoring revealed adequate voriconazole plasma trough concentrations (0.98 mg/L) 30 days after dose reduction and no more colonies of Aspergillus were observed. Voriconazole-induced hepatotoxicity is a well known dose-dependent adverse drug reaction. This experience confirms the appropriateness of voriconazole dose reduction instead of therapy interruption in dose-dependent moderate liver toxicity. Voriconazole therapeutic drug monitoring before and after dose reduction may help to avoid drug accumulation and inappropriately low drug exposure, respectively. [ABSTRACT FROM AUTHOR]

A 44 year old patient with end stage idiopathic pulmonary fibrosis underwent single left lung transplantation. A perfusion lung scan performed 13 days after transplantation revealed deficient perfusion in the transplanted lung. Pulmonary angiography showed severe pulmonary artery anastomotic stenosis. Percutaneous insertion of a balloon expandable stent improved both pulmonary perfusion and respiratory function. [ABSTRACT FROM AUTHOR]