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See detailIs FE(NO50) useful diagnostic tool in suspected asthma?
SCHLEICH, FLorence ULg; ASANDEI, Raluca ULg; Manise, Maïté ULg et al

in International Journal of Clinical Practice (2012), 66(2), 158-65

Background: Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability. Airway inflammation measured by fractional exhaled nitric oxide, measured at a flow rate of ... [more ▼]

Background: Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability. Airway inflammation measured by fractional exhaled nitric oxide, measured at a flow rate of 50 ml/s (FE(NO50) ) remains a controversial diagnostic tool. Aim: To assess the ability of FE(NO50) to identify bronchial hyperresponsiveness (BHR) to methacholine (provocative concentration of methacholine causing a 20% fall in FEV(1) ; PC20M </= 16 mg/ml) and to establish whether or not symptoms relate to FE(NO50) and PC20M in patients with no demonstrated reversibility to beta(2) -agonist. Methods: We conducted a prospective study on 174 steroid naive patients with respiratory symptoms, forced expiratory volume in 1 s (FEV(1) ) >/= 70% predicted and no demonstrated reversibility to beta(2) -agonist. Patients answered to a standardised symptom questionnaire and underwent FE(NO50) and methacholine challenge. Receiver-operating characteristic (ROC) curve and logistic regression analysis assessed the relationship between PC20M and FE(NO50) , taking into account covariates (smoking, atopy, age, gender and FEV(1) ). Results: A total of 82 patients had a PC20M </= 16 mg/ml and had significantly higher FE(NO50) (19 ppb vs. 15 ppb; p < 0.05). By constructing ROC curve, we found that FE(NO50) cut-off value of 34 ppb was able to identify not only BHR with high specificity (95%) and positive predictive value (88%) but low sensitivity (35%) and negative predictive value (62%). When combining all variables into the logistic model, FE(NO50) (p = 0.0011) and FEV(1) (p < 0.0001) were independent predictors of BHR whereas age, gender, smoking and atopy had no influence. The presence of diurnal and nocturnal wheezing was associated with raised FE(NO50) (p < 0.001 and p < 0.05, respectively). Conclusion: The value of FE(NO50) > 34 ppb has high predictive value of PC20M < 16 in patients with suspected asthma in whom bronchodilating test failed to demonstrate reversibility or was not indicated. However, FE(NO50) </= 34 ppb does not rule out BHR and should prompt the clinician to ask for a methacholine challenge. [less ▲]

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See detailDisturbed Cytokine Production at the Systemic Level in Difficult-to-Control Atopic Asthma: Evidence for Raised Interleukin-4 and Decreased Interferon-gamma Release following Lipopolysaccharide Stimulation.
MANISE, Maïté ULg; SCHLEICH, FLorence ULg; QUAEDVLIEG, Valérie ULg et al

in International Archives of Allergy & Immunology (2012), 158(1), 1-8

Background: Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between ... [more ▼]

Background: Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between cytokine production from blood leucocytes and the level of asthma control. Methods: We compared the production of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-gamma and tumour necrosis factor-alpha from peripheral blood leucocytes in non-atopic healthy subjects (n = 22), atopic non-asthmatics (n = 10), well-controlled asthmatics [Juniper asthma control questionnaire (ACQ) score <1.5; n = 20] and patients with uncontrolled asthma despite inhaled or oral corticoids (ACQ score >/=1.5; n = 20). Fifty microlitres of peripheral blood was incubated for 24 h with RPMIc, lipopolysaccharide (LPS; 1 ng/ml) or phytohaemagglutinin (1 mug/ml), and cytokines were measured by immunotrapping (ELISA). Results: Both controlled and uncontrolled asthmatics as well as atopic non-asthmatics spontaneously produced more IL-4 than non-atopic healthy subjects (p < 0.001). IL-4 production induced by LPS was significantly greater (p < 0.05) in both asthma groups compared to atopic non-asthmatics and non-atopic healthy subjects. By contrast, IFN-gamma release induced by LPS was lower in uncontrolled asthmatics than in non-atopic healthy subjects (p < 0.05) and controlled asthmatics (p < 0.05). IL-10 release after LPS was greater in uncontrolled asthmatics than in atopic non-asthmatics (p < 0.05). No difference was observed regarding other cytokines. Conclusion: Blood cells from patients with difficult-to-control atopic asthma display highly skewed Th2 cytokine release following LPS stimulation. [less ▲]

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See detailLocal and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease.
Moermans, Catherine ULg; HEINEN, Vincent ULg; NGUYEN DANG, Delphine ULg et al

in Cytokine (2011), 56(2), 298-304

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease caused by repeated exposure to noxious gases or particles. It is now recognized that the disease also ... [more ▼]

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease caused by repeated exposure to noxious gases or particles. It is now recognized that the disease also features systemic inflammation. The purpose of our study was to compare airway and systemic inflammation in COPD to that seen in healthy subjects and to relate the inflammation with the disease severity. METHODS: Ninety-five COPD patients, encompassing the whole severity spectrum of the disease, were recruited from our outpatient clinic and rehabilitation center and compared to 33 healthy subjects. Induced sputum and blood samples were obtained for measurement of inflammatory cell count. Interleukin (IL)-4, IL-6, IL-10, TNF-alpha and IFN-gamma produced by 24h sputum and blood cell cultures were measured. RESULTS: Compared to healthy subjects, COPD exhibited a prominent airway neutrophilic inflammation associated with a marked IL-10, IL-6 and TNF-alpha release deficiency that contrasted with a raised IFN-gamma production. Neutrophilic inflammation was also prominent at blood level together with raised production of IFN-gamma, IL-10 and TNF-alpha. Furthermore, sputum neutrophilia correlated with disease severity assessed by GOLD stages. Likewise the extent of TNF-alpha release from blood cells also positively correlated with the disease severity but negatively with that of sputum cell culture. Blood release of TNF-alpha and IL-6 negatively correlated with body mass index. Altogether, our results showed a significant relationship between cellular marker in blood and sputum but poor relationship between local and systemic release of cytokines. CONCLUSIONS: COPD is characterized by prominent neutrophilic inflammation and raised IFN-gamma production at both bronchial and systemic level. Overproduction of TNF-alpha at systemic level correlates with disease severity and inversely with body mass index. [less ▲]

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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 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 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 detailGranulocyte chemotactic activity in exhaled breath condensate of healthy subjects and patients with COPD
Corhay, Jean-Louis ULg; Hemelaers; Henket, Monique ULg et al

in CHEST (2007), 131(6), 1672-1677

Background. Several chemoattractants have been measured in exhaled breath condensate (EBC) from patients with COPD. The aim of this study was to compare the eosinophil. and neutrophil chemotactic activity ... [more ▼]

Background. Several chemoattractants have been measured in exhaled breath condensate (EBC) from patients with COPD. The aim of this study was to compare the eosinophil. and neutrophil chemotactic activity contained in EBC from healthy subjects and patients with COPD. Methods: EBC collected using a commercially available condenser (EcoScreen; Erich Jaeger Viasys; Hoechberg, Germany) was compared in 45 COPD patients and 65 healthy subjects. EBC chemotactic activity for eosinophils and neutrophils was assessed using microchambers (Boyden; Neuro Probe; Cabin John, MD). Chemotactic index (CI) was used to evaluate cell migration. Results: EBC from patients with COPD (C1, 2.21 +/- 0.16 [mean +/- SEM]) and healthy subjects (CI, 1.67 +/- 0.11) displayed significant neutrophil chemotactic activity (p < 0.0001 for both), which was however higher in patients with COPD (p < 0.001). Healthy smokers had a significantly raised C1 for neutrophils by comparison with healthy nonsmokers (p < 0.01) and ex-smokers (p < 0.05). Ukewise, current COPD smokers tended to have greater neutrophil C1 than COPD who stopped smoking (p = 0.08). COPD ex-smokers had raised chemotactic activity by comparison with healthy ex-smokers (p < 0.05). Anti-interleuldn-8 (10(-6) g/mL) antibodies reduced neutrophil chemotactic activity by 35.2% (p < 0.05). EBC also contained significant eosinophil chemotactic activity in healthy subjects (CI, 1.68 0.09; p < 0.0001) and patients with COPD (CI, 1.23 +/- 0.07; p < 0.01), with a significantly lower CI in patients with COPD as compared to healthy subjects (p < 0.001). Smoking did not influence eosinophil chemotactic activity in healthy subjects or patients with COPD. Conclusions: Current smoking favors neutrophil chemotactic activity. As compared to healthy subjects, EBC from patients with COPD displays a skewed chemotactic activity toward neutrophils vs eosinophils. [less ▲]

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See detailCytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics
Quaedvlieg, Valérie ULg; Henket, Monique ULg; Sele, Jocelyne ULg et al

in Clinical & Experimental Immunology (2006), 143(1), 161-166

The inflammatory pathways involved in asthma are more complex than the sole Th2-mediated eosinophilic airway inflammation. Different phenotypes of asthma have been recently highlighted and are probably ... [more ▼]

The inflammatory pathways involved in asthma are more complex than the sole Th2-mediated eosinophilic airway inflammation. Different phenotypes of asthma have been recently highlighted and are probably underlied by different immunological profiles. The aim of the study was to assess cytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics. Induced sputum was obtained from 48 consecutive stable mild to moderate asthmatics (20 eosinophilic asthmatics, 28 non-eosinophilic asthmatics) and 31 healthy subjects. Cytokine released from sputum cells were measured by a home-made two-step sandwich immunoassay. Cytokines investigated were interleukin (IL)-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Sputum cells from eosinophilic asthmatics produced more IL-4 than those from both healthy subjects (P < 0.05) and non-eosinophilic asthmatics (P < 0.05). Conversely, sputum cells from eosinophilic asthma were found to release lower amounts of TNF-alpha than those from healthy subjects (P < 0.05). The group of non-eosinophilic asthmatics did not distinguish from healthy subjects with respect to any cytokines measured. Sputum cells from asthmatics exhibiting eosinophilic airway inflammation release more IL-4 and less TNF-alpha than those of healthy subjects. By contrast, non-eosinophilic asthmatics did not distinguish from healthy subjects by abnormal cytokine release from their sputum cells. [less ▲]

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See detailCysteinyl-leukotrienes contribute to sputum eosinophil chemotactic activity in asthmatics
Hemelaers, L.; Henket, Monique ULg; Sele, Jocelyne ULg et al

in Allergy (2006), 61(1), 136-139

Background: Cysteinyl-leukotrienes are lipid derived mediators involved in asthma. They are able to stimulate eosinophil chemotaxis in vitro. Induced sputum from asthmatics has been shown to contain ... [more ▼]

Background: Cysteinyl-leukotrienes are lipid derived mediators involved in asthma. They are able to stimulate eosinophil chemotaxis in vitro. Induced sputum from asthmatics has been shown to contain eosinophil chemotactic activity. The purpose of our study was to evaluate the contribution of cysteinyl-leukotrienes to sputum eosinophil chemotactic activity in asthmatics and to seek whether there might be differences between asthmatics free of inhaled corticosteroids vs those regularly receiving this treatment. Methods: Twenty-two patients (11 corticosteroid free, mean FEV1 99% predicted, 11 corticosteroid-treated, mean FEV1 77% predicted) recruited from our asthma clinic underwent a sputum induction. Sputum was processed according to standard procedure. Eosinophil chemotactic activity contained in the fluid phase was assessed using Boyden microchamber model and expressed as chemotaxis index (CI). Cysteinyl-leukotrienes were measured in sputum supernatant by ELISA and their role in sputum eosionophil chemotactic activity was evaluated by using montelukast, a selective antagonist of a cys-LT1 receptor. Results: Cysteinyl-leukotrienes were well detectable in sputum supernatants from both steroid-naive (247 +/- 42 pg/ml) and steroid-treated (228 +/- 26 pg/ml) asthmatics. Sputum eosinophil chemotactic activity was indiscriminately present in both corticosteroid-naive (CI: 2.61 +/- 0.22) and corticosteroid-treated (2.98 +/- 0.35) asthmatics. Montelukast (100 mu M) significantly inhibited the eosinophil chemotactic activity in both groups achieving a mean inhibition of 54.2 +/- 9.2% (P < 0.001) and 64.7 +/- 7.8% (P < 0.001) in steroid-naive and steroid-treated asthmatics respectively. Conclusion: Cysteinyl-leukotrienes actively participate in sputum eosinophil chemotactic activity found in asthmatics irrespective of whether they are or not under treatment with inhaled corticoids. [less ▲]

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See detailCytokine production from sputum cells after allergenic challenge in IgE-mediated asthma
Bettiol, Jeanne; Sele, Jocelyne ULg; Henket, Monique ULg et al

in Allergy (2002), 57(12), 1145-1150

Background: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways in ammation in allergic asthma. Induced sputum has become a widely used technique to assess airways in ... [more ▼]

Background: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways in ammation in allergic asthma. Induced sputum has become a widely used technique to assess airways in ammation. Methods: By applying the technique of induced sputum to collect airways cells, we have assessed the spontaneous production of a set of cytokines, including interleukin-4, 6, 10, interferon-gamma and tumour necrosis factor-alpha 6 h after a bronchial allergenic hallenge with Dermatophagoides pteronyssinus (Dpt) in 12 sensitized asthmatics and compared the results obtained after inhalation of saline as control. A group of eight healthy non-allergic subjects was enrolled to control for any non-specific effect of Dpt. Cytokines were measured by a dynamic immunoassay during a 24-h sputum cell culture. Results: Allergen challenge in sensitized asthmatics caused an acute and a late bronchospasm together with a rise in sputum eosinophil counts. Afterwards allergen sputum cells from allergic asthmatics displayed a rise in their production of IL-4 (P < 0.01), IL-6 (P < 0.05) and IL- 10 (P < 0.05) when compared to saline. By this time sputum generation of IL- 4 in atopic asthmatics was greater than in healthy subjects (P < 0.001). Furthermore, in allergic asthmatics there was a strong correlation between the rise in interleukin-4 production from sputum cells and the rise in sputum eosinophils (r = 0.87, P < 0.001). Conclusions: Sputum cell culture is a useful model to assess cytokine production in allergic asthmatics who show a marked up-regulation of Th2 cytokines following acute allergen exposure. The rise in sputum eosinophil count following allergen challenge strongly correlates with the rise in IL-4 generation from sputum cells. [less ▲]

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See detailSputum eosinophil count in a large population of patients with mild to moderate steroid-naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness
Louis, Renaud ULg; Sele, Jocelyne ULg; Henket, Monique ULg et al

in Allergy (2002), 57(10), 907-912

BACKGROUND: Although airway eosinophilia is seen as a cardinal feature of asthma, data eosinophilia are still lacking on the proportion of the asthma group exhibiting raised airway eosinophilia. This ... [more ▼]

BACKGROUND: Although airway eosinophilia is seen as a cardinal feature of asthma, data eosinophilia are still lacking on the proportion of the asthma group exhibiting raised airway eosinophilia. This study aimed to assess the distribution of sputum eosinophil count and its relationship with methacholine bronchial hyperresponsiveness in mild to moderate steroid-naive asthmatic people. METHODS: Sputum was induced by inhalation of hypertonic saline (NaCl 4.5%) in 118 mild to moderate steroid-naive asthmatic people consecutively recruited from our outpatient clinic, and in 44 healthy people. The asthma group was selected on the basis of an forced expiratory volume in 1 s (FEV(1)) of > or = 70% predicted, and a provocative methacholine concentration causing a fall of 20% in FEV(1) (PC20 methacholine; PC(20)M) < or = 16 mg/ml. RESULTS: In the asthma group, the median (range) of the percentage and the absolute values of sputum eosinophils were 4.8% (0-75) and 38 10(3)/g (0-14,191), respectively, vs 0% (0-2.3) (P < 0.001) and 0 10(3)/g (0-53) (P < 0.001) in healthy participants. Based on the 95% percentile for normal values calculated from our healthy group, 69% of the asthma group had significantly raised sputum eosinophil count (that is > 2%). In the asthma group, multiple regression analysis followed by a stepwise procedure revealed that sputum eosinophil count was significantly and inversely associated with PC(20)M accounting for 16% of its total variance (P < 0.001) while neutrophil counts positively related to PC(20)M accounting for 4% of total variance (P < 0.05). By contrast, no significant relationship was found between either eosinophil or neutrophil counts and the slope of forced vital capacity (FVC) vs FEV(1) from the methacholine challenge. CONCLUSIONS: We conclude that two-thirds of people in the mild to moderate asthma group had increased sputum eosinophilia, which plays a limited role in determining the degree of methacholine airway hyperresponsiveness. [less ▲]

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See detailEvidence of mast-cell activation in a subset of patients with eosinophilic chronic obstructive pulmonary disease
Louis, Renaud ULg; Cataldo, Didier ULg; Buckley, M. G. et al

in European Respiratory Journal (2002), 20(2), 325-331

Although asthma has been viewed mainly, as an eosinophilic disease, and chronic obstructive pulmonary disease (COPD) as a neutrophilic disease, recent studies have shown increased neutrophil counts in ... [more ▼]

Although asthma has been viewed mainly, as an eosinophilic disease, and chronic obstructive pulmonary disease (COPD) as a neutrophilic disease, recent studies have shown increased neutrophil counts in severe asthma and sputum eosinophilia in sonic COPD patients. In an attempt to further characterise these two syndromes according to pathology, the current authors have conducted a study of induced sputum in 15 subjects with COPD, 17 asthmatics, and 17 nonatopic healthy individuals. Sputum was analysed for cytology and levels of eosinophil cationic protein (ECP), albumin, tryptase and soluble intercellular adhesion molecule-1. The COPD subjects differed from the asthmatics as they had higher sputum neutrophil and lower columnar epithelial cell counts, but there were no differences in any soluble marker studied. When compared to control subjects, both the asthmatic and COPD subjects had raised eosinophil counts and ECP levels. In a subset of COPD subjects with Sputum eosinophilia (>3% of total cells), significantly increased levels of tryptase were detected. In conclusion, although chronic obstructive pulmonary disease is a more neutrophilic disease than asthma, the two diseases are difficult to distinguish on the basis of sputum levels of the soluble markers traditionally associated with asthma. However, a subset of patients with chronic obstructive pulmonary disease with airway eosinophilia and mast-cell activation might represent a distinct pathological phenotype. [less ▲]

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See detailEffect of a 4-Week Treatment with Theophylline on Sputum Eosinophilia and Sputum Eosinophil Chemotactic Activity in Steroid-Naive Asthmatics
Louis, Renaud ULg; Bettiol, J.; Cataldo, Didier ULg et al

in Clinical & Experimental Allergy : Journal of the British Society for Allergy & Clinical Immunology (2000), 30(8), 1151-60

BACKGROUND: The precise mechanism of action of theophylline in asthma is not fully understood but recent data have drawn attention to its potential anti-inflammatory effect. OBJECTIVE: The purpose of this ... [more ▼]

BACKGROUND: The precise mechanism of action of theophylline in asthma is not fully understood but recent data have drawn attention to its potential anti-inflammatory effect. OBJECTIVE: The purpose of this study was to assess the effect of theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid-naive asthmatics. METHOD: We performed a 4-week randomized double-blind, placebo-controlled, parallel group study in 21 mild to moderate steroid-naive asthmatics whose sputum eosinophilia was found twice > 5% during the run in period. Eleven subjects received 600 mg/24 h theophylline for the first 2 weeks and 900 mg/24 h for the last 2 weeks while 10 subjects took a placebo for 4 weeks. Sputum was induced after 2 and 4 weeks of treatment and 1 week after stopping the treatment. The sputum samples were compared for their cell counts, eosinophil cationic protein (ECP) levels and eosinophil chemotactic activity using micro-Boyden chambers. RESULTS: Serum theophylline concentrations reached 7 and 11 microg/mL at V3 and V4, respectively. Intragroup comparisons showed that theophylline, but not placebo, caused a significant reduction in sputum eosinophil counts at V3 (62 +/- 10% from baseline, P < 0.01) and a strong trend at V4 (67 +/- 16% from baseline, P = 0.07) when compared to baseline. The intergroup difference obtained after comparing the area under the curve over the 4 week treatment period only approached the statistical significance (P = 0.08). At baseline the fluid phase of the sputum contained a significant eosinophil chemotactic activity which was inhibited after a 4-week treatment by theophylline (P < 0. 01) but not by placebo. The mean sputum theophylline levels after 4 weeks of treament (1.7 microg/mL) was lower than that required to cause significant inhibition of eosinophil chemotaxis in vitro. CONCLUSION: Theophylline decreases the natural sputum eosinophil chemotactic activity present in asthmatics. However, when using a small sample size, the 35% reduction in sputum eosinophilia achieved by theophylline failed to reach statistical significance when compared to that seen after placebo. [less ▲]

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See detailAirway Mast-Cell Activation in Asthmatics Is Associated with Selective Sputum Eosinophilia
Bettiol, Jane; Radermecker, Maurice ULg; Sele, Jocelyne ULg et al

in Allergy (1999), 54(11), 1188-93

BACKGROUND: Tryptase is a serine endoprotease selectively released from mast cells. Although mast cells are known to be activated after experimental allergic provocation, their role in naturally occurring ... [more ▼]

BACKGROUND: Tryptase is a serine endoprotease selectively released from mast cells. Although mast cells are known to be activated after experimental allergic provocation, their role in naturally occurring asthma is still debated. METHODS: We have investigated the levels of tryptase in the whole induced sputum collected from 51 asthmatics (31 atopic and 20 intrinsic) seen in our outpatient clinic and 22 normal nonatopic healthy volunteers. Tryptase was measured by a new immunoassay based on B12 monoclonal antibody recognition of total tryptase (UniCAP System, Pharmacia) with a sensitivity of 1 ng/ml. RESULTS: While being below the threshold of detection in all normal volunteers, tryptase was detectable in the sputum from 9/51 asthmatics (18%) including five atopic and four intrinsic asthma cases. In these patients, among whom three were asymptomatic asthmatics, the values ranged between 1 and 6.1 ng/ml. The asthmatics with detectable sputum tryptase had greater sputum eosinophil counts (P<0.05) but lower neutrophil counts (P<0.05) than those in whom tryptase was undetectable. When compared to control subjects, asthmatics without tryptase had still greater eosinophil counts (P<0.0001) but also raised neutrophil counts (P<0.05). No significant difference could be found between asthmatics with tryptase and those without tryptase with respect to the age, the baseline lung function, the methacholine bronchial responsiveness, and the frequency of treatment with inhaled steroids. CONCLUSIONS: With the UniCAP System, tryptase was detectable in the sputum from 18% of asthmatics irrespective of atopy and current symptoms. Asthmatics with tryptase appeared to have a selective increase in sputum eosinophil counts while those without tryptase displayed a mixed sputum granulocyte infiltration with raised eosinophil and neutrophil counts. [less ▲]

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See detailIn Vitro Propagated Dendritic Cells from Patients with Human-Papilloma Virus-Associated Preneoplastic Lesions of the Uterine Cervix: Use of Flt3 Ligand
Hubert, Pascale ULg; Greimers, Roland ULg; Franzen-Detrooz, E. et al

in Cancer Immunology, Immunotherapy (1998), 47(2), 81-9

Dendritic cells (DC) are the most efficient antigen presenting cells. The clinical use of DC as vectors for antitumor and anti-infectious disease immunotherapy has been limited by their low level and ... [more ▼]

Dendritic cells (DC) are the most efficient antigen presenting cells. The clinical use of DC as vectors for antitumor and anti-infectious disease immunotherapy has been limited by their low level and accessibility in normal tissue. Substantial numbers of DC can be generated from peripheral blood cultured in the presence of interleukin-4 (IL-4) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). We showed in this study that substantial numbers of DC can be obtained from the peripheral blood of patients with (pre)neoplastic lesions of the uterine cervix. The procedure required relatively small blood samples (10 ml) and the presence of 100 U/ml IL-4 and 800 U/ml GM-CSF in the culture medium. There was no significant difference in the morphology, yield, phenotype and function of generated DC between patients with cervical (pre)neoplastic lesions and healthy individuals. When the hematopoietic factor Flt3 ligand (Flt3L, 40 ng;ml) was added, there was an average increase in the DC population of 26% compared to cultures with GM-CSF and IL-4 alone. Approximately 1.2 x 10(6) cells with the characteristics of dendritic cells could be obtained when Flt3L was included in the medium. The addition of Flt3L did not modify the phenotypic profile of DC (HLA-DR+, CD1a+, CD4+, CD54+, CD80+, CD86+. CD40+, CD3- and CD14-). In addition, Flt3L generated functional DC capable of stimulating the proliferation of alloreactive T cells. These results suggest that Flt3L, in association with GM-CSF and IL-4, provides an advantageous tool for the large-scale generation of DC and that an immunotherapy based on the use of DC generated in vitro is possible in patients with (pre)neoplastic lesions of the uterine cervix. [less ▲]

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