Disturbed 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 ; SCHLEICH, FLorence ; QUAEDVLIEG, Valérie 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 ▲]Detailed reference viewed: 27 (5 ULg)
Exhaled nitric oxide thresholds associated with a sputum eosinophil count >=3% in a cohort of unselected patients with asthma.
Schleich, FLorence ; Seidel, Laurence ; Sele, Jocelyne 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 ▲]Detailed reference viewed: 47 (19 ULg)
Association between asthma control and bronchial hyperresponsiveness and airways inflammation: a cross-sectional study in daily practice.
Quaedvlieg, Valérie ; Sele, Jocelyne ; Henket, Monique 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 ▲]Detailed reference viewed: 43 (6 ULg)
Cytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics
Quaedvlieg, Valérie ; Henket, Monique ; Sele, Jocelyne 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 ▲]Detailed reference viewed: 22 (5 ULg)
Le cas clinique du mois: Clarte pulmonaire unilaterale.
Quaedvlieg, Valérie ; Duysinx, Bernard ; Ghaye, Benoît et al
in Revue Médicale de Liège (2004), 59(12), 691-4
MacLeod syndrome is a rare cause of localized hypertransradiancy of the lung. This syndrome is defined by radiological features: localized hypertransradiancy due to oligemia and presence of air-trapping ... [more ▼]
MacLeod syndrome is a rare cause of localized hypertransradiancy of the lung. This syndrome is defined by radiological features: localized hypertransradiancy due to oligemia and presence of air-trapping on expiratory chest radiography. Involvement of one entire lung is called "unilateral hyperlucent lung". Whereas the etiology is different, the physiopathology is probably identical to that of the panacinar emphysema of chronic obstructive pulmonary disease. The syndrome is believed to be related to acute bronchiolitis during infancy. Clinical manifestations and prognosis depend mainly on the presence of other lesions due to the same infectious agent like bronchiectasis. Pulmonary function tests, chest CT-scan, ventilation and perfusion scintigraphy and, if necessary, bronchoscopy help the differential diagnosis and detect associated bronchiectasis. [less ▲]Detailed reference viewed: 88 (2 ULg)
Phase II trial exploring gemcitabine and cisplatin as treatment of patients with non-small cell lung cancer (NSCLC) and inoperable brain metastases
Barthelemy, Nicole ; Bosquee, Léon ; Quaedvlieg, Valérie
in Lung Cancer (2003), 41(supp2), 145Detailed reference viewed: 6 (1 ULg)
Les cysteinyl-leucotrienes: des mediateurs importants dans l'asthme
Louis, Renaud ; ; Quaedvlieg, Valérie et al
in Revue Médicale de Liège (1997), 52(9), 598-602Detailed reference viewed: 20 (0 ULg)