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Biomedical subjects

R Louis

Publications and source records attributed to R Louis.

At least 19 recordsLinked to original sources
PubMed2006

Differences in local versus systemic TNFalpha production in COPD: inhibitory effect of hyaluronan on LPS induced blood cell TNFalpha release.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by both airway inflammation and systemic changes. To elucidate the relationship between local and systemic inflammation, tumour necrosis factor alpha (TNFalpha) production by sputum cells and blood cells of patients with COPD and controls was compared and the effect of the extracellular matrix compound hyaluronan (HA) on TNFalpha release was studied. METHODS: Four study groups were included: 10 steroid free COPD patients, 8 steroid treated patients, 10 healthy smokers, and 11 healthy non-smokers. Sputum cells and blood were incubated for 24 hours with or without lipopolysaccharide (LPS) in the absence or presence of HA (122 kDa or HMW fragment). TNFalpha was measured by ELISA. RESULTS: Sputum cells produced spontaneously high levels of TNFalpha but were unresponsive to LPS. Sputum cells from COPD patients (both steroid free and steroid treated) produced significantly less TNFalpha than cells from healthy non-smoking subjects (p=0.017 and p=0.001, respectively). In contrast, blood cells produced TNFalpha only in response to LPS. No differences were observed in TNFalpha production by blood cells between the patient groups and the control groups. HA (both fragments) partially blocked LPS (1 ng/ml) induced TNFalpha release by blood cells from all study groups, whereas TNFalpha production by sputum cells was not influenced by HA. CONCLUSION: These data indicate a difference between local and systemic TNFalpha production. Sputum cells of patients with COPD produced less TNFalpha than controls, which could contribute to impaired local defence. An inhibitory effect of HA on TNFalpha release in blood cells was observed which was similar in both patients and controls.

Adult↗
PubMed2006

Cytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics.

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.

Adult↗
PubMed2006

Cysteinyl-leukotrienes contribute to sputum eosinophil chemotactic activity in asthmatics.

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 microM) 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.

Adult↗
PubMed2006

[Stop smoking help: keys to long term success].

This review deals with the pharmacological and psychological means to help in smoking cessation and compares the efficacy of the different methods. Pharmacological support results in a smoking cessation rate reaching at best 20-25%. The efficacy of behavioural and cognitive therapy have been much less validated so far. Multidisciplinary specialized centres for helping smokers have been raised under the care of FARES in the French Community of Belgium.

Cognitive Behavioral Therapy↗
PubMed2006

[Exhaled nitric oxide: a new biomarker for respiratory pathologies].

There has been a growing interest for exhaled biomarkers. We review studies examining NO as a potential marker of airway inflammation, enabling noninvasive repeated monitoring of airway inflammation. The measurement technique has been standardized. We have determined the local normal levels for the Liège region. The exhaled NO level is elevated in asthma, and can predict asthma exacerbation. Exhaled NO has a value for the diagnosis of cystic fibrosis and primary ciliary dyskinesia.

Asthma↗
PubMed2006

[Asthma and tobacco].

Roughly 40% of asthmatics are or have been smokers. These smoking asthmatics have been largely overlooked in the past. Tobacco is today considered as a risk factor for asthma and it seems that smoking asthmatics exhibit a different phenotype as compared to non smoking asthmatics. The inflammatory substrate differs widely, not only with respect to the type of cells present in the airways, but also with respect to the mediators brought into play. On the clinical point of view the asthma of smokers is also more severe that in non smokers, both at the symptomatic and the functional level. The asthma severity in smokers is partly linked to a resistance to inhaled corticoids, the cornerstone of maintenance treatment in asthma. This makes urgent to assess alternative treatment to inhaled corticoids for this asthma phenotype, but also emphasizes the need to support smoking cessation in asthmatics.

Adrenal Cortex Hormones↗
PubMed2006

[Eotaxin: an important chemokine in asthma].

We know that the eosinophil plays an important role in asthma pathogenesis. This polynuclear cell is attracted into the airways by several chemokines. Eotaxin is one of them. Endothelial cells, smooth muscle cells, epithelial cells, alveolar macrophages and eosinophils can produce eotaxin. In asthmatic airways, eotaxin production is increased in bronchial airway lumen and mucosa. Eotaxine actively participates in asthma pathogenesis by activating eosinophil recruitment.

Asthma↗
PubMed2006

[Exacerbations in COPD: a burden to curtail].

Exacerbations of chronic obstructive pulmonary disease (COPD) play a very important role. Unfortunately they were neglected a long time in the therapeutic tests. However exacerbations influence the decline of the respiratory function over time, cause important deterioration of the quality of life of the patients, increase morbidity and mortality of COPD, and finally represent a burden for health care. Reducing the number of exacerbations could potentially slow down the progression of the disease. Thus the prevention of exacerbations should be the "corner stone" of the maintenance treatment of the COPD. In this review we propose to recall the importance of exacerbations in COPD and to present the treatment which have been shown to reduce exacerbation rate in COPD.

Humans↗
PubMed2005

The triple neurokinin-receptor antagonist CS-003 inhibits neurokinin A-induced bronchoconstriction in patients with asthma.

Neurokinin A (NKA) causes bronchoconstriction in asthmatic patients. In vitro both NK1 and NK2 receptors can mediate airway contraction. Moreover in guinea pigs, NK3 receptors facilitate cholinergic neurotransmission. Dual tachykinin NK1/NK2 receptor antagonism results in prevention of NKA-induced bronchoconstriction. We have now examined the effect of a single dose of the triple tachykinin receptor antagonist CS-003 on NKA-induced bronchoconstriction in asthmatics. A double blind, crossover, placebo-controlled trial in 16 mild asthmatics was performed. One single dose of CS-003 (200 mg, solution in distilled water) or matched placebo was given orally on the assessment days. NKA-provocation tests were performed pre-dose and 1, 8 and 24 h after dosing. There was a significant shift to the right of the dose-response curve at 1 and 8 h after intake of CS-003. PC20 was not reached in 12/16 patients at 1h post-dose and in 5/16 patients at 8 h post-dose. This did not occur under placebo treatment. A single dose of 200 mg CS-003 protected significantly against NKA-induced bronchoconstriction at 1 and 8h post-dose in mild asthmatics.

Adolescent↗
PubMed2005

[Tiotropium: a new therapeutic option in chronic obstructive pulmonary disease].

Tiotropium is a long-acting anticholinergic bronchodilator, inhaled only once a day, which produces relaxation of airway smooth muscle through antagonism of acetylcholine at M3-muscarinic receptors. Its duration of action is at least 24 h with once daily administration of tiotropium. Several studies have shown its efficacy and its good tolerance in the treatment of patients who are suffering from moderate to very severe chronic obstructive pulmonary disease (COPD). Tiotropium improves spirometric measurements and quality of life, and reduces dyspnea and exacerbation rate in COPD patients.

Administration, Inhalation↗
PubMed2005

[Control of gene transcription as a new therapeutic target in asthma].

The recent advances in the knowledge of the molecular mechanisms underlying asthma have lead to a significant improvement of the current treatments of the disease and opened new perspectives for the development of therapeutic alternatives to inhaled corticosteroids. The selective targeting of transcription factors controlling the expression of the genes implicated in the pathogenesis of asthma is one of these privileged strategies. This review aims at describing the most promising new therapeutic targets in the control of asthmatic inflammation at the gene transcription level.

Asthma↗
PubMed2005

[Stop smoking help: a need].

Today the smoker carries a risk of mortality 70% higher compared to the nonsmoker. In Belgium active smoking is indisputably the most important cause of avoidable death. In 2004 it appears that 27% of the belgian population was smoking. This review describes the comorbidity associated with active tobacco consumption and defines the concepts of dependence and smoking cessation. It also identifies the three factors which determine the success of smoking cessation, i.e. the degree of nicotinic dependence, the presence of anxio-depressive disorders and the importance of the motivation to the stop.

Belgium↗
PubMed2004

Nebulised salbutamol administered during sputum induction improves bronchoprotection in patients with asthma.

BACKGROUND: Inhalation of hypertonic or even isotonic saline during sputum induction may cause bronchospasm in susceptible patients with asthma, despite premedication with 400 microg inhaled salbutamol delivered by pressurised metered dose inhaler (pMDI). The bronchoprotection afforded by additional inhaled salbutamol administered through the ultrasonic nebuliser during sputum induction was investigated. METHODS: Twenty patients with moderate to severe asthma underwent sputum induction by inhaling saline 4.5% (or 0.9% if post-bronchodilation forced expiratory volume in 1 second (FEV1) <65% predicted) for 10 minutes according to two protocols given 1 week apart in random order. At visit A the patients received 400 microg salbutamol administered through a pMDI+spacer 20 minutes before induction while at visit B the premedication was supplemented by 1500 microg nebulised salbutamol inhaled throughout the induction procedure. Both the investigator and the patients were blind to the nebulised solution used. FEV1 was recorded during sputum induction at 1, 3, 5, and 10 minutes. Sputum cell counts and histamine, tryptase and albumin levels in the supernatants were determined. RESULTS: The mean (SE) maximal reduction in FEV1 over the 10 minute period of sputum induction was 11.7 (2.8)% at visit A, which was significantly greater than at visit B (2.6 (1.2)%; mean difference 9% (95% CI 2.7 to 15.4), p<0.01). Total and differential sputum cell counts as well as albumin, tryptase, and histamine levels did not differ between the two visits. CONCLUSION: The addition of inhaled salbutamol through an ultrasonic nebuliser markedly improves bronchoprotection against saline induced bronchoconstriction in patients with moderate to severe asthma undergoing sputum induction without affecting cell counts and inflammatory markers.

Administration, Inhalation↗
PubMed2004

Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients.

Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK1 and NK2 receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK1/NK2 receptor antagonist, DNK333, on NKA-induced bronchoconstriction in asthma. A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled crossover trial. Increasing concentrations of NKA (3.3x10(-9) to 1.0x10(-6) mol x mLP(-1)) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo. It was observed that DNK333 did not affect baseline lung function but did protect against NKA-induced bronchoconstriction in those patients. The mean log10 provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was -5.6 log10 mol x mL(-1) at 1 h after DNK333 treatment and -6.8 log10 mol x mL(-1) after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment. The results shown in this report indicate that DNK333 blocks neurokinin A-induced bronchoconstriction in patients with asthma.

Administration, Inhalation↗