Anti-Inflammatory Effect of Fluvastatin on IL-8 Production Induced by Pseudomonas aeruginosa and Aspergillus fumigatus Antigens in Cystic Fibrosis

International audienceBACKGROUND: Early in life, patients with cystic fibrosis (CF) are infected with microorganisms including bacteria and fungi, particularly Pseudomonas aeruginosa and Aspergillus fumigatus. Since recent research has identified the anti-inflammatory properties of statins (besides their lipid-lowering effects), we investigated the effect of fluvastatin on the production of the potent neutrophil chemoattractant chemokine, IL-8, in whole blood from CF patients, stimulated by Pseudomonas aeruginosa (LPS) and Aspergillus fumigatus (AFA) antigens. RESULTS: Whole blood from adult patients with CF and from healthy volunteers was collected at the Rennes University Hospital (France). Blood was pretreated for 1 h with fluvastatin (0-300 µM) and incubated for 24 h with LPS (10 µg/mL) and/or AFA (diluted 1/200). IL-8 protein levels, quantified by ELISA, were increased in a concentration-dependent manner when cells were stimulated by LPS or AFA. Fluvastatin strongly decreased the levels of IL-8, in a concentration-dependent manner, in whole blood from CF patients. However, its inhibitory effect was decreased or absent in whole blood from healthy subjects. Furthermore, the inhibition induced by fluvastatin in CF whole blood was reversed in the presence of intermediates within the cholesterol biosynthesis pathway, mevalonate, farnesyl pyprophosphate or geranylgeranyl pyrophosphate that activate small GTPases by isoprenylation. CONCLUSIONS: For the first time, the inhibitory effects of fluvastatin on CF systemic inflammation may reveal the important therapeutic potential of statins in pathological conditions associated with the over-production of pro-inflammatory cytokines and chemokines as observed during the manifestation of CF. The anti-inflammatory effect could be related to the modulation of the prenylation of signalling proteins

Normalisation ventilatoire après réduction de volume pulmonaire naturelle consécutive à une infection pulmonaire

National audienceIntroduction - Lung volume reduction can be effective in appropriately selected patients with severe emphysema and is associated with reduced breathlessness and improved survival. Spontaneous resolution of emphysematous bullae can also sometimes occur. Case report - We report a case of severe smoking-related emphysema in a 60-year-old patient, who presented in October 2013 with a right upper lobe acute community-acquired pneumonia on the background of previously undocumented emphysema. The patient improved following treatment with co-amoxiclav and serial radiology showed progressive cicatricial retraction. Nine months later there had been a major functional improvement characterized by a complete normalization of the patient's ventilatory parameters, specifically a 45% improvement in FEV. In the literature, the average FEV1 improvement obtained by surgical or endoscopic lung volume reduction techniques does not exceed 28%. Conclusion - Rarely, emphysematous bullae resolve following infections. Further studies of the mechanisms involved in these natural regressions may be of interest in the development of new therapeutics

Effect of continuous versus intermittent subglottic suctioning on tracheal mucosa by the mallinckrodt taperguard evac oral tracheal tube in intensive care unit ventilated patients A prospective randomized study

International audienceBackground and Aims: A risk of tracheal mucosa injury induced by subglottic suctioning has been raised. Therefore, this prospective randomized study aims to compare the effect of continuous suctioning of subglottic secretions versus intermittent suctioning of subglottic secretions (CSSS vs. ISSS) secretions on tracheal mucosa in front of the suctioning port of the endotracheal tube.Patients and Methods: Patients requiring intubation or reintubation in Intensive Care Unit with an expected ventilation duration > 24 h were eligible. Participants received CSSS at -20 mmHg or ISSS at -100 mmHg during 15 s and no suction during 8 s. The effect on tracheal mucosa in front of the suction port was assessed after intubation (T0) and before extubation (T1) using bronchoscopy. Tracheal mucosa damages were graded into five categories (no injury, erythema, edema, ulceration, or necrosis). The occurrence (no injury observed at T0 but present at T1) or the worsening (injury observed at T0 exacerbating at T1) was studied.Results: Seventy-three patients were included and 53 patients (CSSS, n = 26 and ISSS, n = 27) were evaluable on the primary endpoint. The occurrence or worsening of tracheal mucosal damages did not differ between the two groups (CSSS, n = 7 [27%] vs. ISSS, n = 5 [17%], P = 0.465). Daily average volume of suctioned secretion was higher with ISSS (74 ± 100 ml vs. 20 ± 25 ml, P < 0.001). Impossibility to aspirate was higher with CSSS (0.14 ± 0.16 per day vs. 0.03 ± 0.07 per day, P < 0.001).Conclusions: Our results suggest that tracheal mucosal damages did not differ between CSSS and ISSS. The aspirated volume was higher and impossibility to aspirate was lower with ISSS.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01555229

Étude AIRBAg : résultats préliminaires après un an de dépistage de la BPCO agricole [AIRBAg study: Preliminary results after one year of screening for COPD in dairy farmers]

National audienceINTRODUCTION:The AIRBAg study screens for bronchial obstruction in dairy farmers. We present the preliminary results after one year.METHODS:A prospective screening study based on questionnaires and electronic mini-spirometry (Néo-6(®)) that includes a representative sample of dairy farmers from the departments of Morbihan and Île-et-Vilaine in Brittany. The dairy farmers had an occupational medicine appointment and, if they demonstrated at least one marker of possible bronchial obstruction (chronic cough, chronic bronchitis, dyspnoea, wheezing, FEV1/FEV6<0.8), they were referred to a pulmonologist. The data we present here were extracted from the occupational medicine appointments because the pulmonologists' appointments are still running.RESULTS:Among the 277 dairy farmers included, 125 (45%) demonstrated "possible bronchial obstruction". The total score of the CAT questionnaire was higher in these farmers (9.1±6.2 versus 5.8±4.0; P<0.0001). In multivariate analysis markers of "possible bronchial obstruction" were eczema, manual foddering and duration of mechanical straw litter spreading.CONCLUSION:Occupational medicine appointments identified markers of "possible bronchial obstruction". We will have the complete results from AIRBAg study in 2015

Impact of current cough on health-related quality of life in patients with COPD

Ga&euml;tan Deslee,1 Pierre-R&eacute;gis Burgel,2 Roger Escamilla,3 Pascal Chanez,4 Isabelle Court-Fortune,5 Pascale Nesme-Meyer,6 Graziella Brinchault-Rabin,7 Thierry Perez,8 Gilles Jebrak,9 Denis Caillaud,10 Jean-Louis Paillasseur,11 Nicolas Roche2On behalf of the Initiatives BPCO Scientific Committee 1Department of Respiratory Diseases, INSERM UMR 903, Maison Blanche Hospital, University Hospital of Reims, Reims, 2Department of Respiratory Diseases, Cochin Hospital, AP-HP and University Paris Descartes, Sorbonne Paris Cit&eacute;, Paris, 3Department of Respiratory Diseases, Larrey Hospital, Toulouse, 4Department of Respiratory Diseases, APHM, INSERM U1077, CNRS UMR 7733 Aix Marseille Universit&eacute;, Marseille, 5Department of Respiratory Diseases, University Hospital of St Etienne, 6Department of Respiratory Diseases, La Croix Rousse Hospital, Lyon, 7Department of Respiratory Diseases, Pontchaillou Hospital, University Hospital of Rennes, Rennes, 8Department of Respiratory Diseases, Calmette Hospital, University Hospital of Lille, Lille, 9Department of Respiratory Diseases, Bichat Hospital, AP-HP, Paris, 10Department of Respiratory Diseases, Gabriel Montpied Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, 11EFFI-STAT, Paris,&nbsp;FranceBackground: Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD.Methods: A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities.Results: One hundred and seventy-eight stable COPD patients were included (age, 62 [56&ndash;69]&nbsp;years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37&ndash;72] % predicted) (median [Q1&ndash;Q3]). In univariate analyses, health-related quality of life (Saint George&rsquo;s respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety. All four domains introduced separately were independently associated with health-related quality of life. When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60). With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54).Conclusion: This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients.Keywords: signs and symptoms, respiratory, sputum, questionnaires, dyspnea, multivariate analysi

POSTER 26 sCD14 in macrophages from patients with cystic fibrosis: Origin and involvement in inflammatory functions

International audienc