L'obstruction bronchique dans la bronchopneumopathie chronique obstructive (évaluation fonctionnelle, réversibilité et relations avec la dyspnée)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Severe toxoplasmosis in immunocompetent hosts: be aware of atypical strains.

International audienc

Impact of domestic mould exposure on Aspergillus biomarkers and lung function in patients with chronic obstructive pulmonary disease

International audiencePatients with chronic obstructive pulmonary disease (COPD) are frequently colonised or sensitised by Aspergillus, but clinical significance remains unclear. Furthermore, little is known on the impact of indoor mould exposure during COPD. In this study, we assessed the relationship between domestic mould exposure, Aspergillus biomarkers and COPD severity during acute exacerbation and at stable state. Aspergillus section Fumigati culture in sputum and anti-Aspergillus antibodies detection (IgG and precipitins) were followed up in COPD patients that were prospectively recruited during exacerbation (n = 62), and underwent a visit at stable state after 18 months (n = 33). Clinical characteristics were collected at inclusion. Electrostatic dust collectors (EDCs) were used to measure domestic mould contamination. Aspergillus section Fumigati was more frequently detected during exacerbation (16.9%) than at stable state (4.0%), but the frequency of patients presenting with anti-Aspergillus antibodies was similar (32.2% and 33.3%, respectively). Aspergillus section Fumigati detection was associated with a higher body-mass index (BMI) during exacerbation, whereas patients with anti-Aspergillus antibodies presented a lower BMI and forced expiratory volume in 1 s, as well as a higher frequency of inhaled corticoids and higher total mould and Penicillium exposure at final visit (P 30 CFU/cm2 (P = 0.03). Aspergillosis was diagnosed in 2 patients (6.1%) who presented increased levels of antibodies. Our data suggest that anti-Aspergillus antibodies are associated with chronic lung function alteration and/or domestic mould exposure, thereby supporting the consideration of indoor mould contamination and anti-Aspergillus antibodies kinetics in COPD management

Factors associated with Pneumocystis colonization and circulating genotypes in chronic obstructive pulmonary disease patients with acute exacerbation or at stable state and their homes

International audienceAbstract Pneumocystis jirovecii colonization is frequent during chronic obstructive pulmonary disease (COPD) and patients constitute potential contributors to its interhuman circulation. However, the existence of an environmental reservoir cannot be excluded. We assessed the prevalence and factors associated with Pneumocystis colonization during COPD, and studied circulation between patients and their domestic environment. Pneumocystis molecular detection and mtLSU genotyping were performed in oro-pharyngeal washes (OPW) sampled in 58 patients with COPD acute exacerbation, and in indoor dust, sampled in patients’ homes using electrostatic dust collectors (EDCs). Lung and systemic inflammation was assessed. Pneumocystis carriage was evaluated in 28 patients after 18 months at stable state. Pneumocystis was detected in 11/58 OPWs during exacerbation (19.0%). Colonized patients presented a significantly lower body mass index, and higher serum IL-17 and CD62P. One patient presented positive detection of typable isolates in both OPW and EDC, with both isolates harboring mtLSU genotype 3. Pneumocystis genotype 1 was further detected in EDCs from three non-colonized patients and one colonized patient with non-typable isolate. Genotypes 1 and 2 were predominant in clinical isolates (both 42%), with genotype 3 representing 16% of isolates. Pneumocystis was detected in 3/28 patients at stable state (10.7%). These data suggest that Pneumocystis colonization could be facilitated by a lower BMI and be related to acute alteration of lung function during COPD exacerbation. It also suggests Th17 pathway and platelet activation could be involved in the anti-Pneumocystis response during colonization. Last, Pneumocystis detection in EDCs supports its potential persistence in indoor dust. Lay Summary Chronic obstructive pulmonary disease patients tend to be more frequently colonized by Pneumocystis during exacerbation (19.0%) than at stable state (10.7%). Factors associated with colonization include lower BMI, higher IL-17, and CD62P. Pneumocystis detection in patients’ dwellings suggests potential persistence in indoor dust

Circulation de Pneumocystis entre les patients atteints de BPCO et leur environnement domestique

International audienc

Cigarette smoke alters the ability of human dendritic cells to promote anti-Streptococcus pneumoniae Th17 response

International audienceAbstractBackgroundChronic obstructive pulmonary disease (COPD) is associated with chronic inflammation and impaired immune response to pathogens leading to bacteria-induced exacerbation of the disease. A defect in Th17 cytokines in response to Streptococcus pneumoniae, a bacteria associated with COPD exacerbations, has been recently reported. Dendritic cells (DC) are professional antigen presenting cells that drive T-cells differentiation and activation. In this study, we hypothesized that exposure to cigarette smoke, the main risk factor of COPD, might altered the pro-Th17 response to S. pneumoniae in COPD patients and human DC.MethodsPro-Th1 and -Th17 cytokine production by peripheral blood mononuclear cells (PBMC) from COPD patients was analyzed and compared to those from smokers and non-smokers healthy subjects. The effect of cigarette smoke extract (CSE) was analyzed on human monocyte-derived DC (MDDC) from controls exposed or not to S. pneumoniae. Bacteria endocytosis, maturation of MDDC and secretion of cytokines were assessed by flow cytometry and ELISA, respectively. Implication of the oxidative stress was analyzed by addition of antioxidants and mitochondria inhibitors. In parallel, MDDC were cocultured with autologous T-cells to analyze the consequence on Th1 and Th17 cytokine production.ResultsPBMC from COPD patients exhibited defective production of IL-1β, IL-6, IL-12 and IL-23 to S. pneumoniae compared to healthy subjects and smokers. CSE significantly reduced S. pneumoniae-induced MDDC maturation, secretion of pro-Th1 and -Th17 cytokines and activation of Th1 and Th17 T-cell responses. CSE exposure was also associated with sustained CXCL8 secretion, bacteria endocytosis and mitochondrial oxidative stress. Antioxidants did not reverse these effects. Inhibitors of mitochondrial electron transport chain partly reproduced inhibition of S. pneumoniae-induced MDDC maturation but had no effect on cytokine secretion and T cell activation.ConclusionsWe observed a defective pro-Th1 and -Th17 response to bacteria in COPD patients. CSE exposure was associated with an inhibition of DC capacity to activate antigen specific T-cell response, an effect that seems to be not only related to oxidative stress. These results suggest that new therapeutics boosting this response in DC may be helpful to improve treatment of COPD exacerbations

Antiplatelet Drugs and Risk of Bleeding After Bedside Pleural Procedures: A National Multicenter Cohort Study

International audienceBackground: The decision-making on antiplatelet drug withdrawal or continuation before performing a pleural procedure is based on the balance between the risk of bleeding associated with the antiplatelet therapy and the risk of arterial thrombosis due to its interruption. Knowledge on antiplatelet therapy-associated risk of bleeding after pleural procedures is lacking.Research question: Is the risk of bleeding associated with antiplatelet drugs increased in patients undergoing pleural procedures?Study design and methods: We conducted a French multicenter cohort study in 19 centers. The main outcome was the occurrence of bleeding, defined as hematoma, hemoptysis, or hemothorax, during the 24 h following a pleural procedure. Serious bleeding events were defined as bleeding requiring blood transfusion, respiratory support, endotracheal intubation, embolization, or surgery, or as death.Results: A total of 1,124 patients was included (men, 66%; median age, 62.6 ± 27.7 years), of whom 182 were receiving antiplatelet therapy and 942 were not. Fifteen patients experienced a bleeding event, including eight serious bleeding events. The 24-h incidence of bleeding was 3.23% (95% CI, 1.08%-5.91%) in the antiplatelet group and 0.96% (95% CI, 0.43%-1.60%) in the control group. The occurrence of bleeding events was significantly associated with antiplatelet therapy in univariate analysis (OR, 3.44; 95% CI, 1.14-9.66; P = .021) and multivariate analysis (OR, 4.13; 95% CI, 1.01-17.03; P = .044) after adjusting for demographic data and the main risk factors for bleeding. Likewise, antiplatelet therapy was significantly associated with serious bleeding in univariate analysis (OR, 8.61; 95% CI, 2.09-42.3; P = .003) and multivariate analysis (OR, 7.27; 95% CI, 1.18-56.1; P = .032) after adjusting for the number of risk factors for bleeding.Interpretation: Antiplatelet therapy was associated with an increased risk of post-pleural procedure bleeding and serious bleeding. Future guidelines should take into account these results for patient safety

Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole, Rana esculenta

Human ventilation at rest exhibits mathematical chaos-like complexity that can be described as long-term unpredictability mediated (in whole or in part) by some low-dimensional nonlinear deterministic process. Although various physiological and pathological situations can affect respiratory complexity, the underlying mechanisms remain incompletely elucidated. If such chaos-like complexity is an intrinsic property of central respiratory generators, it should appear or increase when these structures mature or are stimulated. To test this hypothesis, we employed the isolated tadpole brainstem model [Rana (Pelophylax) esculenta] and recorded the neural respiratory output (buccal and lung rhythms) of pre- (n = 8) and postmetamorphic tadpoles (n = 8), at physiologic (7.8) and acidic pH (7.4). We analyzed the root mean square of the cranial nerve V or VII neurograms. Development and acidosis had no effect on buccal period. Lung frequency increased with development (P < 0.0001). It also increased with acidosis, but in postmetamorphic tadpoles only (P < 0.05). The noise-titration technique evidenced low-dimensional nonlinearities in all the postmetamorphic brainstems, at both pH. Chaos-like complexity, assessed through the noise limit, increased from pH 7.8 to pH 7.4 (P < 0.01). In contrast, linear models best fitted the ventilatory rhythm in all but one of the premetamorphic preparations at pH 7.8 (P < 0.005 vs. postmetamorphic) and in four at pH 7.4 (not significant vs. postmetamorphic). Therefore, in a lower vertebrate model, the brainstem respiratory central rhythm generator accounts for ventilatory chaos-like complexity, especially in the postmetamorphic stage and at low pH. According to the ventilatory generators homology theory, this may also be the case in mammals

Additional file 4: of Cigarette smoke alters the ability of human dendritic cells to promote anti-Streptococcus pneumoniae Th17 response

In vitro exposure to cigarette smoke extract (CSE) modulate the phenotype of monocyte-derived dendritic cells (MDDC) from healthy subjects activated by LPS. Expression of CD83 (a), HLA-DR (b), CD80 (c), CD86 (d), CD40 (e) and CD54 (f) was evaluated by flow cytometry in MDDC exposed to CSE and then activated or not by LPS for 24 h. Data are reported as mean fluorescence intensity (MFI) ± S.E.M. of 20 experiments. *P < 0.05, **P < 0.01, ***P < 0.001. (PDF 44 kb