NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma.
; ; et al
in Expert opinion on drug delivery (2014), 11(9), 1497-506
INTRODUCTION: Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic ... [more ▼]
INTRODUCTION: Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic asthmatic inflammation. It is important, therefore, to target the small as well as the large airways in any strategy for effective treatment of this disease. AREAS COVERED: The present review deals with the recently developed fixed dose drug combination of beclometasone dipropionate/formoterol fumarate that emits extrafine particles when delivered from an innovative dry powder inhaler (DPI), NEXThaler(R). The aim is to present the technical and clinical aspects of aerosolized drug delivery to the lungs. EXPERT OPINION: The data show that the NEXThaler DPI is an efficient device for the management of persistent asthma. The evaluation of the inhalation profiles through the NEXThaler DPI demonstrates that device activation and consistent dose delivery occurs at patient achievable inhalation flow rates, and supports the broad utility of the NEXThaler DPI in patients with asthma. Overall, all the effectiveness, efficiency and satisfaction outcomes demonstrate the NEXThaler DPI is easy to use. [less ▲]Detailed reference viewed: 30 (0 ULg)
Thermoplastie bronchique : une réelle avancée dans le traitement de l'asthme
HEINEN, Vincent ; SCHLEICH, FLorence ; DUYSINX, Bernard et al
in Revue Médicale Suisse (2014), 10(439), 1544-1548
New treatments are needed to improve the care of severe asthmatic patients. Bronchial thermoplasty aims to lessen the airway smooth muscles via the heating of bronchial walls by radiofrequency. The ... [more ▼]
New treatments are needed to improve the care of severe asthmatic patients. Bronchial thermoplasty aims to lessen the airway smooth muscles via the heating of bronchial walls by radiofrequency. The preliminary studies showed a good tolerance and some good efficacy. Randomized controlled trials have been undertaken on moderate to severe asthmatic patients, demonstrating an improvement in quality of life, rate of severe exacerbations and unscheduled medical visits. The main side-effects consist of asthma exacerbations, atelectasis and infections. Bronchial thermoplasty is an innovative treatment with good efficacy and acceptable tolerance for moderate to severe asthmatic patients. More studies are needed to better understand its mechanism of action and more clearly delineate the precise indications of this innovative technique. [less ▲]Detailed reference viewed: 30 (5 ULg)
Integrated care pathways for airway diseases (AIRWAYS-ICPs).
; ; et al
in The European respiratory journal (2014), 44(2), 304-23
The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and ... [more ▼]
The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers). [less ▲]Detailed reference viewed: 23 (0 ULg)
Phenotypes de la broncho-pneumopathie chronique obstructive.
Corhay, Jean-Louis ; SCHLEICH, FLorence ; Louis, Renaud
in Revue medicale de Liege (2014), 69(7-8), 415-21
Chronic Obstructive Pulmonary Disease (COPD) is a multi-dimensional disorder with multiple phenotypes. The GOLD guidelines, used for the diagnosis, staging and treatment of COPD, do not fully reflect the ... [more ▼]
Chronic Obstructive Pulmonary Disease (COPD) is a multi-dimensional disorder with multiple phenotypes. The GOLD guidelines, used for the diagnosis, staging and treatment of COPD, do not fully reflect the heterogeneous nature of the disease. Historically, the two most recognized clinical phenotypes of COPD are emphysema and chronic bronchitis. Most COPD patients encountered in practice actually share, both of these features. Genetic background, clinical presentation, variation in the response to treatment and propensity to exacerbations may also identify other phenotypes. Recently, using a mathematical approach, such as cluster analysis, which is based on pre-selected parameters, other interesting phenotypes were identified. A precise definition of COPD phenotypes should lead to a more targeted therapeutic approach based on these phenotypes. The purpose of this article is to point out that COPD is a heterogeneous disease and to summarize the current data available about the phenotypes of this disease. [less ▲]Detailed reference viewed: 32 (9 ULg)
Exhaled Air Analysis for Early Detection of Lung Cancer
Pesesse, Romain ; Stefanuto, Pierre-Hugues ; SCHLEICH, FLorence et al
Poster (2014, May 23)Detailed reference viewed: 44 (7 ULg)
Le cas clinique du mois. Maladie de Carrington: pneumopathie chronique idiopathique à eosinophiles.
; FRUSCH, Nicolas ; DUYSINX, Bernard et al
in Revue medicale de Liege (2014), 69(3), 126-31
Idiopathic Chronic Eosinophilic Pneumonia (ICEP) or Carrington's disease is a rare disease, exclusively pulmonary, and of an unknown origin. Connective tissues of the lungs are infiltrated by eosinophilic ... [more ▼]
Idiopathic Chronic Eosinophilic Pneumonia (ICEP) or Carrington's disease is a rare disease, exclusively pulmonary, and of an unknown origin. Connective tissues of the lungs are infiltrated by eosinophilic cell elements. This illness is progressive, consisting of dyspnea, cough and thoracic pain. In addition, the general condition is impaired. The average delay between onset of symptoms and discovery of chest radiographic opacities is often longer than 3-4 months. Symptoms and chest X-ray quickly improve under corticosteroid treatment. In the future, new research could lead to alternative treatments. We report the case of a woman with ICEP. We shall discuss the diagnostic approach, envisage the potential complications and describe the treatment of the disease. [less ▲]Detailed reference viewed: 18 (0 ULg)
Usage of inhalation devices in asthma and chronic obstructive pulmonary disease: a Delphi consensus statement.
; ; Louis, Renaud et al
in Expert opinion on drug delivery (2014), 11(3), 313-23
OBJECTIVES: The study aimed to assess usage of inhalation devices in asthma and chronic obstructive pulmonary disease (COPD). METHODS: In this two-round Delphi survey, 50 experts in asthma and COPD ... [more ▼]
OBJECTIVES: The study aimed to assess usage of inhalation devices in asthma and chronic obstructive pulmonary disease (COPD). METHODS: In this two-round Delphi survey, 50 experts in asthma and COPD completed a 13-item, Internet-based, self-administered questionnaire about choice of inhalation device, training and monitoring of inhalation techniques, the interchangeability and the role of costs in the selection of inhalation devices. For each item, the median (central tendency) and interquartile ranges (degree of consensus) were calculated. RESULTS: Experts considered that the choice of inhalation device was as important as that of active substance (very good consensus) and should be driven by ease of use (good to very good consensus) and teaching (very good consensus). Experts recommended giving oral and visual instructions (good consensus) and systematic monitoring inhalation techniques. Pulmonologists and paramedics have predominantly educational roles (very good consensus). Experts discouraged inhalation device interchangeability (good consensus) and switching for cost reasons (good to very good consensus) without medical consultation (good consensus). CONCLUSIONS: The results of this survey thus suggested that inhalation devices are as important as active substances and training and monitoring are essential in ensuring effective treatment of asthma and COPD. Inhalation device switching without medical consultation should be avoided. [less ▲]Detailed reference viewed: 40 (1 ULg)
Lipid-lowering drug therapies and chronic obstructive pulmonary disease: lung failure or just heart failure?
; Louis, Renaud
in International journal of clinical practice (2014), 68(2), 144-51Detailed reference viewed: 11 (1 ULg)
Adrenomedullin refines mortality prediction by the BODE index in COPD - The "BODE-A" index.
; ; et al
in European Respiratory Journal (2014)
The BODE index is well-validated for mortality prediction in COPD. Concentrations of plasma proadrenomedullin, a surrogate for mature adrenomedullin, independently predicted 2-year mortality among ... [more ▼]
The BODE index is well-validated for mortality prediction in COPD. Concentrations of plasma proadrenomedullin, a surrogate for mature adrenomedullin, independently predicted 2-year mortality among inpatients with COPD exacerbation.We compared accuracy of initial proadrenomedullin level, BODE, and BODE components, alone or combined, in predicting 1-year or 2-year all-cause mortality in a multicenter, multinational observational cohort with stable, moderate to very severe COPD.Proadrenomedullin was significantly associated (P<0.001) with 1-year mortality (4.7%) and 2-year mortality (7.8%), and comparably predictive to BODE regarding both (C statistics: 0.691 vs. 0.745, 0.635 vs. 0.679). Relative to using BODE alone, adding proadrenomedullin significantly improved 1-year and 2-year mortality prognostication (C statistics: 0.750, 0.818; both P<0.001). Proadrenomedullin plus BOD was more predictive than was the original BODE including 6-minute-walk distance. In multivariable analysis, proadrenomedullin (LR X2 13.0, P<0.001), body mass index (8.5, P=0.004), and 6-minute-walk distance (7.5, P=0.006), but not modified MMRC dyspnoea score (2.2, P=0.14) or FEV1 % predicted (0.3, P=0.60), independently foretold 2-year survival.Proadrenomedullin plus BODE better predicts mortality in COPD patients than does BODE alone; proadrenomedullin may substitute for 6-minute-walk distance in BODE when 6-minute-walk testing is unavailable. [less ▲]Detailed reference viewed: 20 (4 ULg)
Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial.
; ; et al
in The Lancet. Oncology (2014), 15(1), 59-68
BACKGROUND: Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves ... [more ▼]
BACKGROUND: Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation. METHODS: The phase 3 START trial was an international, randomised, double-blind trial that recruited patients with unresectable stage III non-small-cell lung cancer who had completed chemoradiotherapy within the 4-12 week window before randomisation and received confirmation of stable disease or objective response. Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy (stable disease vs objective response), delivery of chemoradiotherapy (concurrent vs sequential), and region using block randomisation, and were randomly assigned (2:1, double-blind) by a central interactive voice randomisation system to either tecemotide or placebo. Injections of tecemotide (806 mug lipopeptide) or placebo were given every week for 8 weeks, and then every 6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m(2) (before tecemotide) or saline (before placebo) was given once before the first study drug administration. The primary endpoint was overall survival in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00409188. FINDINGS: From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from the primary analysis population as a result of a clinical hold, resulting in analysis of 829 patients in the tecemotide group and 410 in the placebo group in the modified intention-to-treat population. Median overall survival was 25.6 months (95% CI 22.5-29.2) with tecemotide versus 22.3 months (19.6-25.5) with placebo (adjusted HR 0.88, 0.75-1.03; p=0.123). In the patients who received previous concurrent chemoradiotherapy, median overall survival for the 538 (65%) of 829 patients assigned to tecemotide was 30.8 months (95% CI 25.6-36.8) compared with 20.6 months (17.4-23.9) for the 268 (65%) of 410 patients assigned to placebo (adjusted HR 0.78, 0.64-0.95; p=0.016). In patients who received previous sequential chemoradiotherapy, overall survival did not differ between the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the placebo group (19.4 months [95% CI 17.6-23.1] vs 24.6 months [18.8-33.0], respectively; adjusted HR 1.12, 0.87-1.44; p=0.38). Grade 3-4 adverse events seen with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024 patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia (23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ between groups. INTERPRETATION: We found no significant difference in overall survival with the administration of tecemotide after chemoradiotherapy compared with placebo for all patients with unresectable stage III non-small-cell lung cancer. However, tecemotide might have a role for patients who initially receive concurrent chemoradiotherapy, and further study in this population is warranted. FUNDING: Merck KGaA (Darmstadt, Germany). [less ▲]Detailed reference viewed: 20 (3 ULg)
Importance of concomitant local and systemic eosinophilia in uncontrolled asthma - Letter from the authors to editor
SCHLEICH, FLorence ; LOUIS, Renaud
in The European respiratory journal (2014), 44(4), 1098-9Detailed reference viewed: 18 (2 ULg)
Asthme bronchique non contrôlé : importance des phénotypes et de l'inflammation eosinophilique locale et systémique.
SCHLEICH, FLorence ; LOUIS, Renaud
in Revue Médicale de Liège (2014), 69 Spec No
Asthma is a complex chronic inflammatory disease of the airways. Eosinophilia is a recognized feature of asthma. Asthma is no more considered as a single disease, but there are several subtypes of ... [more ▼]
Asthma is a complex chronic inflammatory disease of the airways. Eosinophilia is a recognized feature of asthma. Asthma is no more considered as a single disease, but there are several subtypes of bronchial asthma, also called phenotypes, that have therapeutic and prognostic implications. Asthmatics are now classified according to inflammatory phenotypes that allow a personalized therapy. Phenotype identification requires induced sputum analysis that is not widely available. In this context, we have identified surrogate markers for inflammatory phenotypes. An eosinophilic phenotype can lbe suspected in case of concomitant increase of exhaled nitric oxide, blood eosinophils, IgE levels and airway obstruction. We have also identified a subgroup of asthmatics exhibiting diffuse local and systemic eosinophilia. This subgroup has a more severe asthma,a lower asthma control and a higher number of exacerbations. [less ▲]Detailed reference viewed: 22 (3 ULg)
Impact of cotransplantation of mesenchymal stem cells on lung function after unrelated allogeneic hematopoietic stem cell transplantation following non-myeloablative conditioning
MOERMANS, Catherine ; LECHANTEUR, Chantal ; BAUDOUX, Etienne et al
in Transplantation (2014), 98(3), 348-353
Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal ... [more ▼]
Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal models, MSC were shown to cause pulmonary alterations after systemic administration. The impact of MSC infusion on lung function has not been studied in humans. The objective of the study was to investigate the impact of MSC co-infusion on lung function and airway inflammation as well as on the incidence of pulmonary infections and cytomegalovirus (CMV) reactivation after HSCT. Methods: We have prospectively followed 30 patients who underwent unrelated HSCT with MSC co-infusion after non-myeloablative conditioning (NMA). Each patient underwent detailed lung function testing (FEV1, FVC, FEV1/FVC, RV, TLC, DLCO and KCO) and measurement of exhaled nitric oxide before HSCT and 3, 6 and 12 months posttransplant. The incidence of pulmonary infections and CMV reactivation were also monitored. This group was compared with another group of 28 patients who underwent the same type of transplantation but without MSC co-infusion. Results: Lung function tests did not show important modifications over time and did not differ between the MSC and control groups. There was a higher 1-year incidence of infection, particularly of fungal infections, in patients having received a MSC co-infusion. There was no difference between groups regarding the 1-year incidence of CMV reactivation. Conclusions: MSC co-infusion does not induce pulmonary deterioration 1 year after HSCT with NMA conditioning. MSC appear to be safe for the lung but close monitoring of pulmonary infections remains essential. [less ▲]Detailed reference viewed: 97 (30 ULg)
Development of recombinant stable house dust mite allergen Der p 3 molecules for component-resolved diagnosis and specific immunotherapy.
; ; et al
in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (2014)
BACKGROUND: The allergen Der p 3 is underrepresented in house dust mite (HDM) extracts probably due to autolysis. Recombinant stable molecule of the allergen is thus needed to improve the diagnosis of ... [more ▼]
BACKGROUND: The allergen Der p 3 is underrepresented in house dust mite (HDM) extracts probably due to autolysis. Recombinant stable molecule of the allergen is thus needed to improve the diagnosis of allergy and the safety and efficacy of immunotherapy. OBJECTIVE: The current study reports the immunological characterization of two recombinant molecules of the HDM allergen Der p 3 as useful tools for diagnosis and immunotherapy. METHODS: Recombinant mature (rDer p 3) and immature (proDer p 3) Der p 3 and their corresponding S196A mutants were produced in Pichia pastoris and purified. The stability, IgE-binding capacity and allergenicity of the different proteins were analyzed and compared with those of the major mite allergen Der p 1 used as a reference. Additionally, the immunogenicity of the different allergens was evaluated in a murine model of Der p 3 sensitization. RESULTS: Compared to the IgE reactivity to recombinant and natural Der p 3 (nDer p 3), the mean IgE binding of patient's sera to rDer p 3-S196A (50 %) was higher. The poorly binding to nDer p 3 or rDer p 3 was due to autolysis of the allergen. Contrary to Der p 3, proDer p 3 displayed very weak IgE reactivity, as measured by sandwich ELISA and competitive inhibition, RBL degranulation and human basophil activation assays. Moreover, proDer p 3 induced a TH 1-biased immune response that prevented an allergic response in mice but retained Der p 3-specific T cell reactivity. CONCLUSION: rDer p 3-S196A should be used for the diagnosis of HDM allergy elicited by Der p 3, and proDer p 3 may represent a hypoallergen of Der p 3. This article is protected by copyright. All rights reserved. [less ▲]Detailed reference viewed: 16 (8 ULg)
Importance of concomitant local and systemic eosinophilia in uncontrolled asthma.
SCHLEICH, FLorence ; ; et al
in The European respiratory journal (2014), 44
Systemic and airway eosinophilia are recognised features of asthma. There are, however, patients who exhibit discordance between local and systemic eosinophilia. In this study, we sought to determine the ... [more ▼]
Systemic and airway eosinophilia are recognised features of asthma. There are, however, patients who exhibit discordance between local and systemic eosinophilia. In this study, we sought to determine the prevalence and characteristics of patients with concordant and discordant systemic and bronchial eosinophilia.We conducted a retrospective study on 508 asthmatics with successful sputum induction. We assessed the relationship between blood and sputum eosinophils by breaking down the population into four groups according to blood (>/=400 cells per mm3) and sputum (>/=3%) eosinophils. Then, we prospectively reassessed the link between eosinophils and asthma control (Asthma Control Questionnaire (ACQ)) and exacerbation rate in a new cohort of 250 matched asthmatics.In our retrospective cohort, asthmatics without eosinophilic inflammation were the largest group (49%). The group with isolated sputum eosinophilia (25%) was, compared with noneosinophilic asthma, associated with lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity ratio and higher bronchial hyperresponsiveness and exhaled nitric oxide fraction (FeNO). Asthmatics exhibiting isolated systemic eosinophilia (7%) had similar characteristics as noneosinophilic asthmatics. The group with concordant systemic and airway eosinophilia (19%) showed remarkable male predominance, and had the lowest airway calibre, ACQ score and quality of life, and the highest bronchial hyperresponsiveness, FeNO and exacerbation rate. The prospective cohort confirmed the different subgroup proportions and the higher ACQ and exacerbation rates in cases of diffuse eosinophilia compared with noneosinophilic asthmatics.Concomitant systemic and bronchial eosinophilic inflammation contribute to poor asthma control. [less ▲]Detailed reference viewed: 36 (27 ULg)
Pleuresies d'etiologie inattendue: le corps etranger au sein de la cavite pleurale.
; HEINEN, Vincent ; Corhay, Jean-Louis et al
in Revue medicale de Liege (2014), 69(1), 38-45
Following three brief clinical reports, we review the literature concerning a rare cause of exudative pleural effusion: the presence of a foreign body in the pleural cavity. Frequently iatrogenical, this ... [more ▼]
Following three brief clinical reports, we review the literature concerning a rare cause of exudative pleural effusion: the presence of a foreign body in the pleural cavity. Frequently iatrogenical, this rare etiology of pleural effusion must be envisaged when this complication develops after any invasive peri-thoracic surgery and must be included in the differential diagnosis of recurrent pleural effusions. These effusions have a favorable prognosis after withdrawal of the foreign body. [less ▲]Detailed reference viewed: 79 (1 ULg)
Pulmonary rehabilitation and COPD: providing patients a good environment for optimizing therapy.
Corhay, Jean-Louis ; NGUYEN DANG, Delphine ; VAN CAUWENBERGE, Hélène et al
in International journal of chronic obstructive pulmonary disease (2014), 9
Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute ... [more ▼]
Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient's disability and poor health-related quality of life (HRQoL). Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation. Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity. Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines. This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. [less ▲]Detailed reference viewed: 31 (6 ULg)
Exertional hypoxemia in stable COPD is common and predicted by circulating proadrenomedullin.
; ; et al
in Chest (2014)
BACKGROUND: The prevalence of exertional hypoxemia in unselected COPD patients is unknown. Intermittent hypoxia leads to adrenomedullin (ADM) up regulation through the HIF-1 pathway. We aimed to assess ... [more ▼]
BACKGROUND: The prevalence of exertional hypoxemia in unselected COPD patients is unknown. Intermittent hypoxia leads to adrenomedullin (ADM) up regulation through the HIF-1 pathway. We aimed to assess the prevalence and the annual probability to develop exertional hypoxemia in stable COPD. We also hypothesized that increased ADM might be associated with exertional hypoxemia and envisioned that adding ADM to clinical variables might improve its prediction in COPD. METHODS: 1233 6-minute walking tests and circulating proadrenomedullin levels from 574 patients with clinically stable, moderate to very severe COPD enrolled in a multinational cohort study and followed-up for 2 years were concomitantly analyzed. RESULTS: The prevalence of exertional hypoxemia was 29.1%. In a matrix derived from a fitted-multi-state model, the annual probability to develop exertional hypoxemia was 21.6%. Exertional hypoxemia was associated with greater deterioration of specific domains of health-related QoL, higher severe exacerbation and death annual rates. In the logistic linear and conditional Cox-regression multivariable analyses, both FEV1% predicted and proADM proved independent predictors of exertional hypoxemia (p<0.001 for both). Adjustment for comorbidities, including cardiovascular disorders, and exacerbation-rate did not influence results. Relative to using FEV1% pred alone, adding proADM resulted in a significant improvement of the predictive properties (p=0.018). Based on the suggested non-linear nomogram, patients with moderate COPD (FEV1 predicted=50%) but high proADM levels (>2nmol/l) presented increased risk (>30%) for exertional desaturation. CONCLUSIONS: Exertional desaturation is common and associated with poorer clinical outcomes in COPD. Adrenomedullin improves prediction of exertional desaturation as compared to the use of FEV1%pred alone. [less ▲]Detailed reference viewed: 21 (6 ULg)
Fibrose mediastinale idiopathique.
; GUIOT, Julien ; et al
in Revue médicale de Liège (2013), 68(7-8), 408-11
Fibrosing mediastinitis is a rare condition characterized by an excessive growth of dense fibrous tissue within the mediastinum. The etiology of the disease is most often a fungal infection and may in ... [more ▼]
Fibrosing mediastinitis is a rare condition characterized by an excessive growth of dense fibrous tissue within the mediastinum. The etiology of the disease is most often a fungal infection and may in some cases be idiopathic. We present the case of a patient with chronic obstructive pulmonary disease (COPD) suffering from fibrosing mediastinitis of undetermined origin and in whom the diagnosis was established by histopathological analysis after mediastinoscopy. [less ▲]Detailed reference viewed: 29 (5 ULg)
Novel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils: a possible biochemical mechanism for allergic eosinophilic inflammation of the airways.
EL SHAZLY, Amr ; Begon, Dominique ; KUSTERMANS, Gaëlle et al
in Journal of Biological Chemistry (2013), 288(2), 1374-84
We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and ... [more ▼]
We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophils cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted into exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted into significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues, showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophils chemotaxis from AR patients and Eol-1 cells, was mediated through CRTH2 receptor. Cells migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition, but not to tyrosine kinase or P38 MAP-kinase inhibition, or calcium chelation. Western blot demonstrated a novel CRTH2 mediated cytosol to membrane translocation of PKC-epsilon, PKC-delta and PKA-alpha, gamma and IIalpha reg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils. [less ▲]Detailed reference viewed: 41 (9 ULg)