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See detailLung function and airway inflammation monitoring after hematopoietic stem cell transplantation.
Moermans, Catherine ULg; Poulet, Christophe ULg; HENKET, Monique ULg et al

in Respiratory Medicine (2013), 107

Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the ... [more ▼]

Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). Methods We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as well as sputum cell counts before and 3, 6, 12, 24 and 36 months after HSCT. Results For the whole cohort there was a progressive decrease in TLC, which was significant after 3 years (p < 0.01). By contrast, there was no change in other lung functions parameters or in FeNO. Baseline sputum analysis revealed increased neutrophil counts in patients {Median (IQR): 63% (38–79)} compared to healthy subjects matched for age {Median (IQR): 49% (17–67), p < 0.001} but there was no significant change in any type of sputum cell counts over the three years. When comparing myeloablative (MA) vs non-myeloablative (NMA) conditioning, falls in FEV1, FVC and DLCO, and rise in RV and sputum neutrophils were more pronounced over the first year of observation in those receiving MA. Conclusions There was a progressive loss in lung function after HSCT, featuring a restrictive pattern. Myeloablative conditioning was associated with early rise of sputum neutrophils and greater alteration in lung function over the first year. [less ▲]

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See detail(Ex-)smoking asthma patients in general and specialized Belgian practice.
Decramer, M.; Louis, Renaud ULg; Joos, G. et al

in Respiratory medicine (2011), 105(8), 1203-1210

INTRODUCTION: Smokers are often excluded from asthma studies. In the present study, data are presented on the prevalence, characteristics and management approach of this patient population in the Belgian ... [more ▼]

INTRODUCTION: Smokers are often excluded from asthma studies. In the present study, data are presented on the prevalence, characteristics and management approach of this patient population in the Belgian practice both at the level of general practitioners (GPs) and specialists. MATERIALS AND METHODS: One hundred and nineteen smoking, non-smoking and ex-smoking patients (25-65 yrs) with asthma, COPD or both, were recruited by 33 GPs and 33 specialists. Data were obtained retrospectively from medical records. However, only a small number of files were complete. RESULTS: The majority of COPD patients were (ex-)smokers: 94% in the specialist group, 78% in the GP group. Cardiovascular comorbidity appeared in both groups in the same frequency order: COPD>(ex-)smoking patients with asthma (AS)>non-smoking patients with asthma (ANS), with a significant difference between AS and ANS in the specialist population. Chronic cough during more than 3 months in two consecutive years was reported in 97% of COPD patients, in 71% of the AS patients and in only 25% of the ANS patients. The type of cough differed between AS and ANS in the GP group, with a higher prevalence of productive cough in the former. Treatment patterns observed were as expected according to diagnosis except for a disproportionate use of Tiotropium in AS in the GP group. CONCLUSION: AS were somewhere in between COPD patients and ANS for a large number of the characteristics studied, suggesting that they are an intermediate phenotype between COPD and asthma. [less ▲]

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See detailHypocortisolism induces chronic respiratory failure
PIRLET, Charles ULg; BECK, Emmanuel ULg; SCHEEN, André ULg et al

in Respiratory Medicine (2011), 4(3), 107-108

Hypocortisolism is an uncommon condition. Its association with myopathy and respiratoryfailure has only rarely been described. We report the case of a 52 year-old woman presenting with progressive ... [more ▼]

Hypocortisolism is an uncommon condition. Its association with myopathy and respiratoryfailure has only rarely been described. We report the case of a 52 year-old woman presenting with progressive dyspnoea. Work-up revealed a severe restrictive syndrome with hypoxaemia. Further investigations showed hypocortisolism of pituitary origin. Response to hydrocortisone allowed us to conclude to an unusual case of hypocortisolic myopathy affecting the respiratory muscles. [less ▲]

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See detail"Real-life" effectiveness of omalizumab in patients with severe persistent allergic asthma: The PERSIST study.
Brusselle, G.; Michils, A.; Louis, Renaud ULg et al

in Respiratory medicine (2009), 103(11), 1633-42

OBJECTIVE: To evaluate the 16- and 52-week effectiveness of add-on omalizumab treatment under real-life heterogeneity in patients, settings, and physicians in an open-label, multicenter, pharmaco ... [more ▼]

OBJECTIVE: To evaluate the 16- and 52-week effectiveness of add-on omalizumab treatment under real-life heterogeneity in patients, settings, and physicians in an open-label, multicenter, pharmaco-epidemiologic study of patients with severe persistent allergic asthma in Belgium. METHODS: Effectiveness outcomes included improvement in 2005 global initiative for asthma (GINA) classification, physician-rated global evaluation of treatment effectiveness (GETE), quality of life (Juniper asthma-related quality of life (AQLQ) and European quality of life questionnaire 5 dimensions (EQ-5D)), and severe asthma exacerbations. Patients studied included both intent-to-treat and per-protocol populations. RESULTS: The sample (n=158) had a mean age of 48.17+/-17.18 years, and a slight majority were female (53.8%). Despite being treated with high-dose inhaled corticosteroids and long-acting beta2-agonists, all patients experienced frequent symptoms and had exacerbations in the past year. At 16 weeks, >82% had good/excellent GETE (P values <0.001), >82% had an improvement in total AQLQ scores of > or =0.5 points (P<0.001), and >91% were severe exacerbation-free (P<0.001). At 52 weeks, >72% had a good/excellent GETE rating (P<0.001), >84% had improvements in total AQLQ score of > or =0.5 points (P<0.001), >56% had minimally important improvements in EQ-5D utility scores (P=0.012), and >65% were severe exacerbation-free (P<0.001). Significant reductions in healthcare utilization compared to the one year prior to treatment were noted. CONCLUSION: The PERSIST study shows better physician-rated effectiveness, greater improvements in quality of life, greater reductions in exacerbation rates, and greater reductions in healthcare utilization than previously reported in efficacy studies. Under real-life conditions, omalizumab is effective as add-on therapy in the treatment of patients with persistent severe allergic asthma. [less ▲]

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See detailBudesonide/formoterol maintenance and reliever therapy versus conventional best practice.
Demoly, Pascal; Louis, Renaud ULg; Soes-Petersen, Ulrik et al

in Respiratory medicine (2009), 103(11), 1623-32

Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) reduces asthma exacerbations and symptoms versus fixed-dose regimens plus short-acting beta(2)-agonists (SABA) in double-blind ... [more ▼]

Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) reduces asthma exacerbations and symptoms versus fixed-dose regimens plus short-acting beta(2)-agonists (SABA) in double-blind trials. Information is lacking regarding its effectiveness versus conventional best practice (CBP). This pooled analysis of six 6-month, randomized, open-label studies examined asthma control and exacerbation risk in asthmatics (aged> or =12 years). Patients (N=7855) symptomatic on inhaled corticosteroids (ICS) or stable/symptomatic on ICS/long-acting beta(2)-agonists (LABA) received budesonide/formoterol maintenance and reliever therapy (160/4.5microg bid and as needed) or CBP (ICS or ICS/LABA+/-other agents at an approved dose plus as-needed SABA). Overall asthma control was assessed comparing the incidence of exacerbations and levels of asthma control using the asthma control questionnaire (ACQ). Budesonide/formoterol maintenance and reliever therapy did not significantly reduce time to first severe exacerbation (primary variable) versus CBP (P=0.062). However, patients in this group experienced 15% fewer exacerbations (0.20 versus 0.24/patient/year; P=0.021) and used 27% less ICS (P<0.0001). Odds of remaining well controlled (ACQ< or =0.75) over 6 months were higher with budesonide/formoterol maintenance and reliever therapy versus CBP (45% versus 41%, odds ratio [OR] 1.29; P<0.01) while risk of remaining uncontrolled decreased (25% versus 29%, OR 0.81; P<0.01). Budesonide/formoterol maintenance and reliever therapy improves key aspects of asthma control versus physicians' choice of CBP. [less ▲]

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See detailDiagnostic value of interleukine-6, transforming growth factor-beta 1 and vascular endothelial growth factor in malignant pleural effusions.
Duysinx, Bernard ULg; Corhay, Jean-Louis ULg; Hubin, Laurent et al

in Respiratory Medicine (2008), 102(12), 1708-14

STUDY OBJECTIVES: We evaluate the accuracy of pleural interleukine-6 (IL-6), transforming growth factor-beta 1 (TGF-beta1), and vascular endothelial growth factor (VEGF) levels for differentiating benign ... [more ▼]

STUDY OBJECTIVES: We evaluate the accuracy of pleural interleukine-6 (IL-6), transforming growth factor-beta 1 (TGF-beta1), and vascular endothelial growth factor (VEGF) levels for differentiating benign from malignant pleural exudates. PATIENTS AND METHODS: Levels of IL-6, TGF-beta1, and VEGF were measured by ELISA in 103 patients with non neutrophilic (<50%) exudative pleurisy including both benign and malignant effusions. Pleurisies were split into benign and malignant according to the pathological diagnosis. RESULTS: Thirty-nine benign (seven infections; 32 inflammatory diseases) and 64 malignant (34 extrathoracic tumors; 25 lung cancers; five mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Pleural reticulo-monocyte count, protein Light's ratio and lactic dehydrogenase Light's ratio were significantly higher in malignant than in benign effusions (p<0.05, p<0.001 and p<0.001, respectively). The median (range) level of VEGF was significantly higher in malignant than in benign effusions (664.50 pg/ml [10-40,143] vs 349 pg/ml [10-8888]) (p<0.05). VEGF levels correlated with pleural LDH (r=0.41, p<0.0001), glucose (r=-0.30, p<0.01) and red cell count (r=0.57, p<0.0001). No significant difference was found between malignant and benign effusions with respect to IL-6 (26.8 ng/ml [1.8-421] vs 18.4 ng/ml [0.45-400], respectively) and TGF-beta1 (1079 pg/ml [18-6206] vs 1123 pg/ml [34-5447]) levels. ROC analysis between benign and malignant pleurisies for VEGF showed an area under the curve of 619 (p=0.03) with a value of 382 pg/ml as the best threshold for distinguishing benign from malignant effusions. CONCLUSIONS: Malignant effusions may enhance the release of VEGF in pleural space and its measurement may help in the diagnosis of malignant effusion. [less ▲]

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See detailPerception of dyspnea in mild smoking asthmatics
Kleis, S.; Chanez, P.; Delvaux, Muriel ULg et al

in Respiratory Medicine (2007), 101(7), 1426-1430

Background: Previous data from the literature reported blunted perception of airway obstruction in severe asthmatics with near fatal asthma. Approximately 25% of patients with asthma are current smokers ... [more ▼]

Background: Previous data from the literature reported blunted perception of airway obstruction in severe asthmatics with near fatal asthma. Approximately 25% of patients with asthma are current smokers. Aim: To determine whether there is an alteration in perception of airway obstruction during a non specific provocative challenge with methacholine in mild controlled asthmatics who smoke. Methods: Enrolled in this study were 50 subjects, including 26 mild asthmatics and 24 healthy subjects, all of them current smokers. The first objective was the sensitivity of airway obstruction calculated by the regression slope linking the change in the visual analogic scale (VAS) assessed by the patient and the fall in FEV1 during a methacholine challenge. Results: Asthmatics who smoke had a blunted perception of airway obstruction during the bronchial challenge significantly different from that seen in healthy smokers (p = 0.03). This impaired dyspnea perception was inversely related to baseline VAS (r = -0.29, p<0.05) and positively related to baseline FEV1 (r = 0.35, p<0.05). Perception of airway obstruction was not correlated with age, sex, atopy or with airway inflammation features such as exhaled NO or sputum eosinophils. Conclusion: Mild asthmatics who smoke display reduced dyspnea perception during a nonspecific provocative challenge with methacholine. This altered perception of airway obstruction does not relate to airway inflammation. (C) 2007 Elsevier Ltd. All rights reserved. [less ▲]

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See detailSummary of recommendations for the design of clinical trials and the registration of drugs used in the treatment of asthma
Holgate, S. T.; Bousquet, J.; Chung, K. F. et al

in Respiratory Medicine (2004), 98(6), 479-487

With new drugs being introduced to treat asthma it is timely to review criteria that can be used to assess efficacy in clinical trials. Anti-asthma drugs are classified into symptoms-modifying, symptom ... [more ▼]

With new drugs being introduced to treat asthma it is timely to review criteria that can be used to assess efficacy in clinical trials. Anti-asthma drugs are classified into symptoms-modifying, symptom preventers and disease modifying agents. Attention is drawn to the types of experimental evidence required in preclinical studies to support further clinical development of a new therapy. Clinical trials demand careful selection of patients to maximise the strength of the efficacy signal according to the type of trial being designed. While provocation tests are useful in suggesting efficacy, negative tests do not necessarily indicate lack of anti-asthma activity. Therapeutic trial designs need to take account of duration of treatment, dose-response relationships and confirmatory trials. Outcome measures include symptoms, lung function, reduction in concomitant medication, exacerbations, quality of life and measures of inflammation. Interpretation of results need to include the clinical relevance of any changes as well as statistical significance. Special consideration needs to be given to the evaluation of drugs for acute severe asthma, asthma in children and older people, co-morbidity such as rhinitis, and inhaler devices. As with all drugs introduced into practice, careful attention needs to be paid to both short- and long-term safety. (C) 2004 Elsevier Ltd. All rights reserved. [less ▲]

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