References of "Louis, Renaud"
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See detailInertie et observance therapeutiques en tant que facteurs influencant le controle de l'asthme.
Louis, Renaud ULg; Manise, Maïté ULg; Sele, Jocelyne ULg et al

in Revue Médicale de Liège (2010), 65(5-6), 338-42

Asthma is a chronic inflammatory disease which can be most often adequately controlled by current medications as demonstrated by multiple randomised clinical trials. Yet most of the recent surveys ... [more ▼]

Asthma is a chronic inflammatory disease which can be most often adequately controlled by current medications as demonstrated by multiple randomised clinical trials. Yet most of the recent surveys conducted in the real life setting point to an inadequate control in the majority of asthmatics. In addition to factors linked to the hygiene of life, clinician's inertia and patient's lack of adherence to the treatment certainly contribute to poor asthma control. [less ▲]

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See detailHealth status instrument vs. prognostic instrument for assessing chronic obstructive pulmonary disease in clinical practice.
Louis, Renaud ULg; Corhay, Jean-Louis ULg

in International Journal of Clinical Practice (2010), 64(11), 1465-6

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See detailMMP-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-induced Airway Inflammation.
Guéders, Maud ULg; Hirst, S.; Quesada Calvo, Florence ULg et al

in American Journal of Respiratory Cell and Molecular Biology (2010), 43(3), 286-95

Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic ... [more ▼]

Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic mediators by cleavage. MMP-19 is a newly described MMP and preferentially cleaves matrix proteins such as collagens and tenascin-C. The role of MMP-19 in asthma has not been described to date. The purpose of the present study was to assess MMP-19 expression in a murine asthma model and to address biological effects of MMP-19 deficiency in mice. Allergenexposed wild-type (WT) mice displayed an increased expression of MMP-19 mRNA and an increased number of MMP-19-positive cells in the lungs detected by immunohistochemistry. After allergen challenge of MMP-19 knockout (MMP-19-/-) mice, an exacerbated eosinophilic inflammation was detected in bronchoalveolar lavage fluid and bronchial tissue along with an increased airway responsiveness to methacholine. A shift towards increased Th2-driven inflammation in MMP-19-/- mice was demonstrated by 1) increased numbers of cells expressing the IL-33 receptor T1/ST2 in lung parenchyma, 2) increased IgG1 levels in serum and 3) higher levels of IL-13 and CCL11 in lung extracts. Tenascin-C was found accumulated in peribronchial areas of MMP-19-/- after allergen challenges as assessed by Western blot and immunohistochemistry analysis. We conclude that MMP-19 is a new mediator in asthma, preventing tenascin-C accumulation and directly or indirectly controlling Th2-driven airway eosinophilia and airway hyperreactivity. Our data suggest that MMP-19 might act on Th2 inflammation homeostasis through preventing tenascin protein accumulation. [less ▲]

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See detailExhaled nitric oxide thresholds associated with a sputum eosinophil count >=3% in a cohort of unselected patients with asthma.
Schleich, FLorence ULg; Seidel, Laurence ULg; Sele, Jocelyne ULg et al

in Thorax (2010), 65(12), 1039-1044

Background It has been claimed that exhaled nitric oxide (FeNO) could be regarded as a surrogate marker for sputum eosinophil count in patients with asthma. However, the FeNO threshold value that ... [more ▼]

Background It has been claimed that exhaled nitric oxide (FeNO) could be regarded as a surrogate marker for sputum eosinophil count in patients with asthma. However, the FeNO threshold value that identifies a sputum eosinophil count >/=3% in an unselected population of patients with asthma has been poorly studied. Methods This retrospective study was conducted in 295 patients with asthma aged 15-84 years recruited from the asthma clinic of University Hospital of Liege. Receiver-operating characteristic (ROC) curve and logistic regression analysis were used to assess the relationship between sputum eosinophil count and FeNO, taking into account covariates such as inhaled corticosteroids (ICS), smoking, atopy, age and sex. Results Derived from the ROC curve, FeNO >/=41 ppb gave 65% sensitivity and 79% specificity (AUC=0.777, p=0.0001) for identifying a sputum eosinophil count >/=3%. Using logistic regression analysis, a threshold of 42 ppb was found to discriminate between eosinophilic and non-eosinophilic asthma (p<0.0001). Patients receiving high doses of ICS (>/=1000 mug beclometasone) had a significantly lower FeNO threshold (27 ppb) than the rest of the group (48 ppb, p<0.05). Atopy also significantly altered the threshold (49 ppb for atopic vs 30 ppb for non-atopic patients, p<0.05) and there was a trend for a lower threshold in smokers (27 ppb) compared with non-smokers (46 ppb, p=0.066). Age and sex did not affect the relationship between FeNO and sputum eosinophilia. When combining all variables into the logistic model, FeNO (p<0.0001), high-dose ICS (p<0.05) and smoking (p<0.05) were independent predictors of sputum eosinophilia, while there was a trend for atopy (p=0.086). Conclusion FeNO is able to identify a sputum eosinophil count >/=3% with reasonable accuracy and thresholds which vary according to dose of ICS, smoking and atopy. [less ▲]

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See detailThe impact of concomitant rhinitis on asthma-related quality of life and asthma control.
Vandenplas, O.; Dramaix, M.; Joos, G. et al

in Allergy (2010)

To cite this article: Vandenplas O, Dramaix M, Joos G, Louis R, Michils A, Verleden G, Vincken W, Vints A-M, Herbots E, Bachert C. The impact of concomitant rhinitis on asthma-related quality of life and ... [more ▼]

To cite this article: Vandenplas O, Dramaix M, Joos G, Louis R, Michils A, Verleden G, Vincken W, Vints A-M, Herbots E, Bachert C. The impact of concomitant rhinitis on asthma-related quality of life and asthma control. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02365.x. Abstract Background: Characterizing the interactions between the upper and lower airways is important for the management of asthma. This study aimed at assessing the specific impact of concomitant rhinitis on asthma-related quality of life (QOL) and asthma control. Methods: A cross-sectional, observational survey was conducted among 1173 patients with asthma (aged 12-45) recruited by general practitioners and chest physicians. AR was defined by self-reported rhinitis symptoms and previously documented sensitization to inhalant allergens. The primary outcomes were (1) asthma control assessed by the Asthma Control Questionnaire (ACQ) and (2) asthma-specific QOL evaluated through the Mini Asthma Quality of Life Questionnaire (mAQLQ). Results: AR was present in 73.9% of the population with asthma and nonallergic rhinitis (NAR) in 13.6%. AR and NAR were associated with an increased risk of uncontrolled asthma (i.e. ACQ score > 1.5) with adjusted odds ratios (OR) of 2.00 (95% confidence interval [CI]: 1.35-2.97) and 1.77 (95%CI: 1.09-2.89), respectively. Multivariate linear regression analysis showed that AR and NAR had a modest, although significant, negative impact on the global mAQLQ score (beta coefficient: -0.293, standard error [SE]: 0.063 and beta coefficient: -0.221, SE: 0.080, P < 0.001, respectively), even after adjustment for the level of asthma control and demographic characteristics. Conclusion: This survey provides direct evidence that AR and NAR are associated with an incremental adverse impact on the disease-specific QOL of patients with asthma and the level of asthma control. Further investigations are required to determine whether appropriate treatment of rhinitis would efficiently reduce asthma morbidity. [less ▲]

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See detailCytokine production from sputum cells and blood leukocytes in asthmatics according to disease severity.
Manise, Maïté ULg; Schleich, FLorence ULg; Gusbin, Natacha ULg et al

in Allergy (2010), 65(7), 889-96

BACKGROUND: Although mild to moderate asthma is known to be Th2 driven, cytokines produced in refractory asthma might not fit the classical Th2 pattern. METHODS: The aim of our study was to assess the ... [more ▼]

BACKGROUND: Although mild to moderate asthma is known to be Th2 driven, cytokines produced in refractory asthma might not fit the classical Th2 pattern. METHODS: The aim of our study was to assess the cytokine production by sputum and blood cells from 15 refractory asthmatics (American Thoracic Society Criteria) compared to 15 mild untreated and 17 moderate treated asthmatics and 22 healthy subjects. Spontaneous production of interleukin (IL)-4, IL-6, IL-10, interferon-gamma, and tumor necrosis factor alpha was measured by immunotrapping after 24 h sputum or blood cell culture. RESULTS: Moderate and refractory asthmatics were both characterized by a lower production of IL-6 from their airway cells compared to healthy subjects. However, the difference was no longer significant when expressing the results per gram of sputum. No significant difference between the three groups was found regarding other cytokines. As for cytokine production from blood, the three groups of asthmatics exhibited raised production of IL-4 when compared to healthy subjects, and this was true when results were expressed per blood volume or after normalization for total leukocyte cell count. Moderate asthmatics exhibited greater production of IL-10 when compared to refractory asthmatics and healthy subjects when results were normalized for total leukocyte cell count. CONCLUSIONS: Sputum cells from moderate and refractory asthmatics release less IL-6. While the systemic overproduction of IL-4 was observed through the all spectrum of asthma severity, moderate asthmatics exhibited greater systemic IL-10 production compared to refractory asthmatics. [less ▲]

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See detailBiomarker discovery in asthma-related inflammation and remodeling.
Quesada Calvo, Florence ULg; Fillet, Marianne ULg; De Seny, Dominique ULg et al

in Proteomics (2009), 9(8), 2163-2170

Asthma is a complex inflammatory disease of airways. A network of reciprocal interactions between inflammatory cells, peptidic mediators, extracellular matrix components, and proteases is thought to be ... [more ▼]

Asthma is a complex inflammatory disease of airways. A network of reciprocal interactions between inflammatory cells, peptidic mediators, extracellular matrix components, and proteases is thought to be involved in the installation and maintenance of asthma-related airway inflammation and remodeling. To date, new proteic mediators displaying significant activity in the pathophysiology of asthma are still to be unveiled. The main objective of this study was to uncover potential target proteins by using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) on lung samples from mouse models of allergen-induced airway inflammation and remodeling. In this model, we pointed out several protein or peptide peaks that were preferentially expressed in diseased mice as compared to controls. We report the identification of different five proteins: found inflammatory zone 1 or RELM (FIZZ-1), calcyclin (S100A6), clara cell secretory protein 10 (CC10), Ubiquitin, and Histone H4. [less ▲]

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See detailSevere asthma: how can we differentiate phenotypes?
Louis, Renaud ULg

in Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology (2009), 139(19-20), 274-7

Difficult-to-treat asthma, severe asthma or refractory asthma are all terms defining a fraction of asthmatics (5-10%) whose asthma cannot be controlled with a combination of high-dose inhaled corticoids ... [more ▼]

Difficult-to-treat asthma, severe asthma or refractory asthma are all terms defining a fraction of asthmatics (5-10%) whose asthma cannot be controlled with a combination of high-dose inhaled corticoids together with long-acting b2 agonists.One major step before claiming that a patient has difficult-to-treat asthma is to ensure that asthma is the correct diagnosis. This involves taking a history of symptoms suggestive of asthma together with objective evidence of variable airflow limitation and/or airway hyperresponsiveness, calling for an intensive initial investigation taking in associated comorbid conditions and multiple re-evaluations over a period of at least 6 months.The pathophysiology of severe/refractory asthma is likely to be different from that of the mild to moderate form. The immune mechanisms underlying the inflammatory process are not purely Th2. The contribution of allergic mechanisms is usually less prominent than in mild to moderate asthma, and other environmental factors such as air pollution, including tobacco smoke and viruses, may be determinant. Involvement of small airways causing air trapping appears to be crucial in making asthma refractory to classic treatment.Several phenotypes have been identified on the basis of demographic, functional, pathological and clinical characteristics, which may sometimes overlap.A cluster analysis has identified two clusters specific to refractory asthma: an early onset symptom-predominant asthma and a late onset inflammation-predominant form.Teasing out mechanisms underlying different phenotypes is essential in finding a new treatment target to improve asthma control in these patients. [less ▲]

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See detailAssociation between asthma control and bronchial hyperresponsiveness and airways inflammation: a cross-sectional study in daily practice.
Quaedvlieg, Valérie ULg; Sele, Jocelyne ULg; Henket, Monique ULg et al

in Clinical & Experimental Allergy : Journal of the British Society for Allergy & Clinical Immunology (2009), 39

Summary Background The primary end-point in the management of asthma is to obtain optimal control. The aim of this study was to assess the relationships between the markers of airway inflammation (sputum ... [more ▼]

Summary Background The primary end-point in the management of asthma is to obtain optimal control. The aim of this study was to assess the relationships between the markers of airway inflammation (sputum eosinophilia and exhaled nitric oxide), bronchial hyperresponsiveness (BHR) and asthma control. Methods One hundred and thirty-four patients were recruited from our asthma clinic between January 2004 and September 2005 [mean age: 42 years, mean forced expiratory volume in 1 s (FEV(1)): 86% predicted]. Eighty-six of them were treated by inhaled corticosteroids, 99 were atopic and 23 were current smokers. They all underwent detailed investigations including fractional-exhaled nitric oxide (FE(NO)) measurement, sputum induction and methacholine challenge when FEV(1) was >70% predicted, and filled in a validated asthma control questionnaire (ACQ6 Juniper). Results When dividing patients into the three groups according to their level of asthma control determined by ACQ [well-controlled asthma (ACQ score </=0.75), borderline (0.75<ACQ score <1.5) and uncontrolled asthma (ACQ score >/=1.5)], it appeared that uncontrolled asthmatics had a greater BHR to methacholine and sputum eosinophilia than controlled asthma (P<0.05, P<0.001, respectively). By contrast, we failed to show significant differences in the FE(NO) levels between the groups. With receiver-operating characteristic curves for differentiating uncontrolled (ACQ>/=1.5) from controlled and borderline (ACQ<1.5) asthma, sputum eosinophilia and methacholine responsiveness were found to be more accurate than FE(NO) (area under the curve: 0.72, 0.72 and 0.59, respectively). Conclusion In a broad spectrum of asthmatics encountered in clinical practice, sputum eosinophilia and methacholine bronchial hyperresponsiveness, but not FE(NO), are associated with uncontrolled asthma. [less ▲]

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See detailLeukotriene B4 Contributes to Exhaled Breath Condensate and Sputum Neutrophil Chemotaxis in COPD.
Corhay, Jean-Louis ULg; Henket, Monique ULg; Nguyen Dang, Delphine ULg et al

in CHEST (2009), 136(4), 1047-1054

Background Neutrophils have been implicated in the pathogenesis of COPD. Several chemoattractants for neutrophils have been measured in exhaled breath condensate (EBC) and induced-sputum (IS) from ... [more ▼]

Background Neutrophils have been implicated in the pathogenesis of COPD. Several chemoattractants for neutrophils have been measured in exhaled breath condensate (EBC) and induced-sputum (IS) from patients with COPD. Objectives The aims of this study were to compare EBC and IS supernatant neutrophil chemotactic activity from ex-smoking COPD and healthy ex-smokers, and to assess the contribution of LTB(4) to this activity. Methods 34 COPD were compared to 24 controls. EBC and IS chemotactic activity for neutrophils were assessed by using Boyden microchambers. Chemotactic index (CI) was used to evaluate cell migration. LTB(4) was measured by a specific enzyme immunoassay. Contribution of LTB4 to EBC and sputum neutrophil chemotaxis was assessed by an LTB(4) receptor antagonist (U-75302: Cayman Chemical Company, Ann Arbor, MI, USA). Results EBC and IS from both COPD and healthy subjects displayed significant neutrophil chemotactic activity but this activity was raised in COPD compared to healthy subjects. Chemotactic activity contained in sputum, however, failed to correlate with that in EBC. In COPD there was a significant correlation between EBC neutrophil chemotactic activity and sputum neutrophil counts. LTB(4) levels were raised in EBC, but not in sputum, from COPD as compared to healthy subjects. LTB(4) receptor antagonist (2.5 10(-4) M) reduced by 44.6% and by 44.4% chemotactic activity contained in EBC and sputum respectively. Conclusions EBC and IS from COPD patients have a raised neutrophil chemotactic activity to which LTB4 contributes. [less ▲]

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See detailInfection par Mycobacterium malmoense chez un sujet immunocompetent.
Guiot, Julien ULg; Ramaut, M.; Massart, B. et al

in Revue Médicale de Liège (2009), 64(7-8), 390-3

We report the case of a 57-year-old patient in whom we found a pulmonary infection due to Mycobacterium malmoense. This patient had no immunodeficiency and responded quite rapidly to anti-tuberculous ... [more ▼]

We report the case of a 57-year-old patient in whom we found a pulmonary infection due to Mycobacterium malmoense. This patient had no immunodeficiency and responded quite rapidly to anti-tuberculous therapy. He was treated for 6 months by levofloxacine, myambutol, and nicotibine, followed by 3 months of clarithromycine, levofloxacine and myambutol. The patient improved clinically to become asymptomatic and the cavitary lesion shown at the CT-scan slightly decreased. The patient is still currently treated by clarithromycine and ciproxine. [less ▲]

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See detailLa vignette therapeutique de l'etudiant. Quand l'asthme se revele.
Louis, Renaud ULg; Schleich, FLorence ULg

in Revue Médicale de Liège (2009), 64(9), 474-8

Asthma is a frequent chronic inflammatory disease which is often mistaken for simple bronchitis. The diagnosis is based on the association of symptoms and excessive airway calibre variability. When ... [more ▼]

Asthma is a frequent chronic inflammatory disease which is often mistaken for simple bronchitis. The diagnosis is based on the association of symptoms and excessive airway calibre variability. When symptoms are present more than once a week, it is recommended to give low dose inhaled corticoids as a maintenance treatment together with, as needed, rapid acting beta2 agonist. In addition it is crucial to provide the patient with an education on the disease to reinforce adherence to the treatment. [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 detailEffects of ciclesonide and fluticasone on cortisol secretion in patients with persistent asthma.
Derom, E.; Louis, Renaud ULg; Tiesler, C. et al

in European Respiratory Journal (2009), 33(6), 1277-86

We compared the systemic and clinical effects of ciclesonide (CIC) and fluticasone propionate (FP) administered, in addition to CIC 160 microg x day(-1) and salmeterol 50 microg twice daily, in 32 ... [more ▼]

We compared the systemic and clinical effects of ciclesonide (CIC) and fluticasone propionate (FP) administered, in addition to CIC 160 microg x day(-1) and salmeterol 50 microg twice daily, in 32 patients with persistent asthma using a randomised double-blind, placebo-controlled, double-dummy, five-period crossover design. All patients exhibited a provocative concentration leading to a 20% decrease in forced expiratory volume in 1 s (PC(20)) methacholine <8 mg x mL(-1) and a PC(20) adenosine <60 mg x mL(-1). Primary outcome was 24-h serum cortisol suppression after 7 days. Secondary outcomes were changes in PC(20) methacholine and adenosine after 9 days. FP 500 microg x day(-1) and 1,000 microg x day(-1) significantly suppressed cortisol secretion versus placebo by -46.2 (95% confidence interval (CI) -83.8- -8.5) nmol x L(-1) and by -76.1 (95% CI -112.9- -39.3) nmol x L(-1), respectively. Neither dose of CIC (320 nor 640 microg x day(-1)) had a significant suppressive effect (-28.2 (95% CI -65.5-9.2) nmol x L(-1) and -37.3 (95% CI -74.7-0.0) nmol x L(-1), respectively). Differences between FP 1,000 microg x day(-1) and both CIC treatments were statistically significant (CIC 320 microg x day(-1): -48.0 (95% CI -84.8- -11.1) nmol x L(-1); CIC 640 microg x day(-1): -38.8 (95% CI -75.7- -1.9) nmol x L(-1)). Compared with placebo, the increase in PC(20) adenosine after the four treatments was small, but significant. Greater improvements in PC(20) adenosine were seen with FP 500 microg x day(-1) (1.8 (95% CI 1.0-2.6) doubling concentrations) compared with CIC 320 microg x day(-1) (0.9 (95% CI 0.1-1.7) doubling concentrations). No significant difference was seen between CIC 640 microg x day(-1) and FP 1,000 microg x day(-1). For a similar decrease in hyperresponsiveness, cortisol secretion was suppressed significantly with moderate-to-high doses of fluticasone propionate, but not with ciclesonide. [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 detailExhaled nitric oxide as a marker of asthma control in smoking patients.
Michils, A.; Louis, Renaud ULg; Peche, R. et al

in European Respiratory Journal (2009), 33(6), 1295-301

Exhaled nitric oxide fraction (F(eNO)), which is a reliable marker of eosinophilic airway inflammation, is partially suppressed by tobacco smoking. Consequently, its potential as a biomarker in asthma ... [more ▼]

Exhaled nitric oxide fraction (F(eNO)), which is a reliable marker of eosinophilic airway inflammation, is partially suppressed by tobacco smoking. Consequently, its potential as a biomarker in asthma management has never been evaluated in smoking patients. In the present study, the authors tested the validity of F(eNO) to predict asthma control in this population. F(eNO) and the Asthma Control Questionnaire (ACQ) were recorded at least once in 411 nonsmoking (345 with at least two visits) and 59 smoking (51 with at least two visits) asthma patients. Despite similar mean ACQ scores (1.5 versus 1.7), F(eNO) was reduced in smoking asthmatics (18.1 ppb versus 33.7 ppb). A decrease in F(eNO) of <20% precludes asthma control improvement in nonsmoking (negative predictive value (NPV) 78%) and in smoking patients (NPV 72%). An increase in F(eNO) <30% is unlikely to be associated with deterioration in asthma control in both groups of patients (NPV = 86% and 84% in nonsmoking and smoking patients, respectively). It is concluded that, even in smokers, sequential changes in F(eNO) have a relationship with asthma control. The present study is the first to indicate that cigarette smoking does not obviate the clinical value of measuring F(eNO) in asthma among smokers. [less ▲]

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See detailL'asthme: une maladie de tout l'arbre aerien.
Tillie-Leblond, I.; Louis, Renaud ULg; Magnan, A. et al

in Revue des Maladies Respiratoires (2009), 26(8), 851-8

Inflammation and remodelling are constant features of asthma. They are present throughout the whole bronchial tree, even in the small airways (less than 2 mm). The inflammatory cell infiltrate and ... [more ▼]

Inflammation and remodelling are constant features of asthma. They are present throughout the whole bronchial tree, even in the small airways (less than 2 mm). The inflammatory cell infiltrate and structural changes are, in most cases, identical. However, in severe asthma, nocturnal asthma and fatal asthma, the cellular infiltrate in the distal airways is more intense and the number of activated cells is increased. In fatal asthma there are major alterations in the distal airways involving the smooth muscle and the bronchial epithelium, and mucus hypersecretion leading to distal airway plugging. Thus the histopathological changes in the distal airways contribute to the most severe stages of asthma and should be targeted by treatment. Currently the non-invasive tools that reflect inflammation are unable to assess these changes in the distal airways. [less ▲]

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See detailL'etude UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium).
Corhay, Jean-Louis ULg; Louis, Renaud ULg

in Revue Médicale de Liège (2009), 64(1), 52-7

The UPLIFT study (Understanding Potential Long-term Impacts on Function with Tiotropium) was a double-blind, randomised, international, multicentric, placebo-controlled clinical trial, investigating with ... [more ▼]

The UPLIFT study (Understanding Potential Long-term Impacts on Function with Tiotropium) was a double-blind, randomised, international, multicentric, placebo-controlled clinical trial, investigating with tiotropium (Spiriva) the change in the annual rate of decline in FEV1 in chronic obstructive pulmonary disease (COPD). Secondary end points included COPD exacerbation rate with or without hospitalisation, lung function, quality of life and mortality. 5.993 patients were randomized. In this article, we briefly describe the most important results of the study. While tiotropium did not alter the annual rate of decline in FEV1 (pre and postbronchodilatation), it improved lung function and quality of life, and reduced exacerbations and hospitalisations by comparison with control for up to 4 years. Tiotropium also reduced respiratory and cardiac morbidity. [less ▲]

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See detailMouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production
Guéders, Maud ULg; Paulissen, Geneviève ULg; Crahay, Céline et al

in Inflammation Research (2009), 58(12), 845-54

Objective Animal models of asthma mimic major features of human disease. Since the genetic background of experimental animals might affect hyperresponsiveness and inflammation, we studied its potential ... [more ▼]

Objective Animal models of asthma mimic major features of human disease. Since the genetic background of experimental animals might affect hyperresponsiveness and inflammation, we studied its potential influence and the mechanisms leading to differences in strains. Methods We applied a mouse model of allergic asthma to BALB/c and C57BL/6 mice. Results BALB/c mice displayed greater levels of airway reactivity to methacholine than C57BL/6 mice. Moreover, BALB/c mice exhibited higher numbers of mast cells in lung tissue when compared to C57BL/6. On the contrary, eosinophil and neutrophil counts in bronchoalveolar lavage fluid (BALF) as well as peribronchial eosinophilia were greater in C57BL/6. IL (Interleukin)-4, IL-5, IL-13, and CCL11 levels measured in whole-lung extracts were higher in BALB/c, while, in sharp contrast, CCL11 and CCL5 levels were higher in BALF of C57BL/6 mice. Conclusions We observed phenotypic differences between C57BL/6 and BALB/c mice in an asthma model with different distributions of pro-inflammatory cytokines and inflammatory cells. [less ▲]

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See detailA comparison of budesonide/formoterol maintenance and reliever therapy vs. conventional best practice in asthma management.
Louis, Renaud ULg; Joos, G.; Michils, A. et al

in International Journal of Clinical Practice (2009), 63(10), 1479-88

OBJECTIVE: To study the effectiveness and safety of budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy (Symbicort SMART, AstraZeneca, Sodertalje, Sweden), a simplified management approach ... [more ▼]

OBJECTIVE: To study the effectiveness and safety of budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy (Symbicort SMART, AstraZeneca, Sodertalje, Sweden), a simplified management approach with one inhaler compared with conventional best practice (CBP) with multiple inhalers in patients with persistent asthma. DESIGN: Open-label randomised controlled parallel group trial, 6-month treatment. PARTICIPANTS: A total of 908 patients > or = 12 years of age, with persistent asthma receiving treatment with inhaled corticosteroids (ICS), either alone or in conjunction with long-acting beta(2)-agonist. MAIN OUTCOME MEASURES: Time to first severe asthma exacerbation and number of severe asthma exacerbations. RESULTS: No difference between groups was seen in time to first severe exacerbation (p = 0.75). Exacerbation rates were low in both groups. A total of 12 patients in the Symbicort SMART group experienced a total of 14 severe asthma exacerbations, and 19 patients in the CBP group experienced a total of 25 severe asthma exacerbations (annual rate 0.07 vs. 0.13 p = 0.09). The mean daily dose of ICS expressed in BDP equivalent was significantly lower in the Symbicort SMART group (including as-needed use) vs. in the CBP group (749 microg vs. 1059 microg; p < 0.0001). Mean scores in Asthma Control Questionnaire, 5 question version improved significantly in the SMART group compared with the CBP group (p = 0.0026). Symbicort SMART and CBP were equally well tolerated. The mean drug cost/patient/month was significantly lower for the patients in the Symbicort SMART group compared with patients receiving CBP (51.3 euros vs. 66.5 euros; p < 0.0001). CONCLUSIONS: In Belgian patients, a simplified regimen using budesonide/formoterol maintenance and reliever therapy was at least as effective at improving clinical control compared with CBP with a significantly lower ICS dose and significantly lower drug costs. [less ▲]

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