L'asthme: une maladie complexe mettant en jeu facteurs environnementaux et terrain genetique.
LOUIS, Renaud ; SCHLEICH, FLorence ; Corhay, Jean-Louis et al
in Revue Médicale de Liège (2012), 67(5-6), 286-91
Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have ... [more ▼]
Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have come out such as ADAM-33 or ORMLD3. Important environmental factors include allergenic exposure, pollutants and especially particulate matters, tobacco, aerosol exposure, viral infections and level of exposure to endotoxin. The effects of environmental factors are modulated by the genetic sequence and numerous single nucleotide polymorphisms (SNPs). Recently, it has also become clear that environmental factors may alter gene expression by DNA methylation or histone methylation/acetylation without changing the gene sequence and thereby changing asthmatic phenotype. [less ▲]Detailed reference viewed: 66 (6 ULg)
Induced sputum: not only for research but also for better patient management in asthma and COPD.
in Monaldi Archives for Chest Disease = Archivio Monaldi per le Malattie del Torace (2012), 77(1), 5-7Detailed reference viewed: 28 (11 ULg)
L'image du mois. Agenesie de l'artere pulmonaire droite associee a une hypoplasie du poumon droit.
FRUSCH, Nicolas ; DUYSINX, Bernard ; BLEUS, Nicolas et al
in Revue Médicale de Liège (2012), 67(1), 4Detailed reference viewed: 38 (10 ULg)
Interrelations genetique- environnement: la broncho-pneumopathie chronique obstructive.
Corhay, Jean-Louis ; ; LOUIS, Renaud
in Revue Médicale de Liège (2012), 67(5-6), 292-7
Smoking is the main environmental risk factor of COPD and accounts for 85% to 90% of COPD. However, 10-15% of COPD patients have never smoked and only a fraction of smokers ever develop COPD. Indeed ... [more ▼]
Smoking is the main environmental risk factor of COPD and accounts for 85% to 90% of COPD. However, 10-15% of COPD patients have never smoked and only a fraction of smokers ever develop COPD. Indeed, genetic and environmental (pollution, occupational and infectious) factors, also influence the risk of developing COPD. Finaly COPD must be considered as the clinical consequence of multiple complex interactions between environmental factors and genetic susceptibility. The latter is not clearly understood, with the exception of alpha-1 antitrypsin deficiency. In this article, we present the different aspects of this complex disease which is primarily environmental. [less ▲]Detailed reference viewed: 25 (6 ULg)
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: 24 (4 ULg)
(Ex-)smoking asthma patients in general and specialized Belgian practice.
; Louis, Renaud ; et al
in Respiratory medicine (2011), 105(8), 1203-1210
INTRODUCTION: Smokers are often excluded from asthma studies. In the present study, data are presented on the prevalence, characteristics and management approach of this patient population in the Belgian ... [more ▼]
INTRODUCTION: Smokers are often excluded from asthma studies. In the present study, data are presented on the prevalence, characteristics and management approach of this patient population in the Belgian practice both at the level of general practitioners (GPs) and specialists. MATERIALS AND METHODS: One hundred and nineteen smoking, non-smoking and ex-smoking patients (25-65 yrs) with asthma, COPD or both, were recruited by 33 GPs and 33 specialists. Data were obtained retrospectively from medical records. However, only a small number of files were complete. RESULTS: The majority of COPD patients were (ex-)smokers: 94% in the specialist group, 78% in the GP group. Cardiovascular comorbidity appeared in both groups in the same frequency order: COPD>(ex-)smoking patients with asthma (AS)>non-smoking patients with asthma (ANS), with a significant difference between AS and ANS in the specialist population. Chronic cough during more than 3 months in two consecutive years was reported in 97% of COPD patients, in 71% of the AS patients and in only 25% of the ANS patients. The type of cough differed between AS and ANS in the GP group, with a higher prevalence of productive cough in the former. Treatment patterns observed were as expected according to diagnosis except for a disproportionate use of Tiotropium in AS in the GP group. CONCLUSION: AS were somewhere in between COPD patients and ANS for a large number of the characteristics studied, suggesting that they are an intermediate phenotype between COPD and asthma. [less ▲]Detailed reference viewed: 26 (16 ULg)
Sirtuin 1 Promotes Th2 Responses and Airway Allergy by Repressing Peroxisome Proliferator-Activated Receptor-γ Activity in Dendritic Cells
; Marichal, Thomas ; Fievez, Laurence et al
in Journal of Immunology (2011), 187(9), 4517-4529
Sirtuins are a unique class of NAD+-dependent deacetylases that regulate diverse biological functions such as aging, metabolism, and stress resistance. Recently, it has been shown that sirtuins may have ... [more ▼]
Sirtuins are a unique class of NAD+-dependent deacetylases that regulate diverse biological functions such as aging, metabolism, and stress resistance. Recently, it has been shown that sirtuins may have anti-inflammatory activities by inhibiting proinflammatory transcription factors such as NF-κB. In contrast, we report in this study that pharmacological inhibition of sirtuins dampens adaptive Th2 responses and subsequent allergic inflammation by interfering with lung dendritic cell (DC) function in a mouse model of airway allergy. Using genetic engineering, we demonstrate that sirtuin 1 represses the activity of the nuclear receptor peroxisome proliferator-activated receptor-γ in DCs, thereby favoring their maturation toward a pro-Th2 phenotype. This study reveals a previously unappreciated function of sirtuin 1 in the regulation of DC function and Th2 responses, thus shedding new light on our current knowledge on the regulation of inflammatory processes by sirtuins. [less ▲]Detailed reference viewed: 35 (13 ULg)
BPCO et inflammation: mise au point d'un groupe d'experts. Les phenotypes en lien avec l'inflammation
; ; et al
in Revue des Maladies Respiratoires (2011), 28(2), 192-215
INTRODUCTION: The objective of the present article is to review available data on possible links between phenotypes and inflammatory profiles in patients with chronic obstructive pulmonary disease (COPD ... [more ▼]
INTRODUCTION: The objective of the present article is to review available data on possible links between phenotypes and inflammatory profiles in patients with chronic obstructive pulmonary disease (COPD). BACKGROUND: Chronic bronchitis is associated with proximal bronchial inflammation and small airway inflammation with remodeling at the site of obstruction. CT scanning enables patients to be phenotyped according to the predominantly bronchial or emphysematous nature of the morphological abnormality. Exacerbations, in a context of persistently elevated baseline inflammation, are associated with increased inflammation and a poor prognosis. Long-term studies have correlated inflammatory markers (and anti-inflammatory drug effects) with dynamic hyperinflation, possibly confirming that inflammation promotes hyperinflation. The inflammatory cell count in the pulmonary arterial walls correlates with the severity of endothelial dysfunction. The risk of developing pulmonary hypertension would seem to increase with low-grade systemic inflammation. The role of low-grade systemic inflammation in COPD co-morbidities, and in nutritional and muscular involvement in particular, remains a matter of debate. Regular physical exercise may help reduce this inflammation. CONCLUSIONS: In COPD, many aspects of the clinical phenotype are related to inflammation. Better knowledge of these relationships could help optimize current and future treatments. [less ▲]Detailed reference viewed: 42 (9 ULg)
Diagnostic value of neurotrophin expression in malignant pleural effusions
DUYSINX, Bernard ; PAULUS, Aurore ; HEINEN, Vincent et al
in Experimental and Therapeutic Medicine (2011), 2(5), 941-946
Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor ... [more ▼]
Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and 4 (nT4)] levels for differentiating benign from malignant pleural exudates. Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%) exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine benign (9 infections and 50 inflammatory diseases) and 111 malignant (50 extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant than in benign effusions [17 pg/ml (0-367) vs. 8 pg/ml (0-51), p<0.05]. ROC analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44 pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in comparison to that in non-squamous cell lung carcinoma (72.7 vs. 10%, p<0.0001). NTs and particularly BDNF may play a role in the pathogenesis of malignant pleural effusions. [less ▲]Detailed reference viewed: 19 (1 ULg)
IFN-gamma and TNF-alpha potentiate prostaglandin D2-induced human eosinophil chemotaxis through up-regulation of CRTH2 surface receptor.
EL SHAZLY, Amr ; MOONEN, Vincent ; et al
in International immunopharmacology (2011), 11(11), 1864-70
Prostaglandin D2 (PGD2) receptor CRTH2, is a pro-inflammatory molecule involved in eosinophil recruitment to the allergic airway. We investigated the expression of CRTH2 in eosinophil from allergic ... [more ▼]
Prostaglandin D2 (PGD2) receptor CRTH2, is a pro-inflammatory molecule involved in eosinophil recruitment to the allergic airway. We investigated the expression of CRTH2 in eosinophil from allergic rhinitis patients (AR) and tested the modulatory role of several TH1 and TH2 cytokines closely related to the allergic immunological response, on the expression of CRTH2 receptor, utilizing human eosinophil cell line (Eol-1).The expression of CRTH2 was tested by immunohistochemistry and flow cytometry (FACS). Chemotaxis was performed in micro-chemotaxis chambers. It is shown that the expression of CRTH2 by eosinophils was significantly higher in the nasal tissue and peripheral blood of AR patients, when compared to control subjects. PGD2 exhibited a typical bell shape dose response in attracting eosinophil from AR patients with optimal activity at 10(-7)M. Eol-1 cell surface expression of CRTH2 was significantly up-regulated by 10ng/ml IFN-gamma and TNF-alpha. The percentage of Eol-1 cells expressing the receptor increased by IFN-gamma and TNF-alpha from 12.74%+/-2.66 to 55%+/-8 and 33.8%+/-9.4, respectively. PGD2-induced Eol-1 chemotaxis was not blocked by SB203580, H-89 Dihydrochloride, Bisindo-lylmaleimide, or Genistein. PGD2-induced Eol-1 chemotaxis was potentiated by IFN-gamma and TNF-alpha without changing the signal transduction pathway. Correlation of our results to peripheral blood eosinophils from allergic rhinitis patients confirmed that 3hour pretreatment of eosinophils by 10ng/ml IFN-gamma and TNF-alpha, increased the mean fluorescence intensity (MFI) of CRTH2 from 8.23 to 9.68 and 9.38, respectively, and potentiated PGD2-induced eosinophil chemotaxis. Our results demonstrate a novel synergism between PGD2, IFN-gamma and TNF-alpha, in eosinophil chemotaxis. [less ▲]Detailed reference viewed: 116 (11 ULg)
Réhabilitation respiratoire dans la bronchopneumopathie chronique obstructive
CORHAY, Jean-Louis ; NGUYEN DANG, Delphine ; BURY, Thierry et al
in EMC Pneumologie (2011)
Le traitement actuel de la bronchopneumopathie chronique obstructive (BPCO) doit comporter, outre un traitement médicamenteux optimal, une réhabilitation respiratoire (RR), de préférence ... [more ▼]
Le traitement actuel de la bronchopneumopathie chronique obstructive (BPCO) doit comporter, outre un traitement médicamenteux optimal, une réhabilitation respiratoire (RR), de préférence multidisciplinaire, et un programme de postrevalidation afin de maintenir les acquis. Il est en effet clairement démontré aujourd'hui que la RR permet d'améliorer la dyspnée, la tolérance à l'effort, l'activité physique et la qualité de vie des patients. De même, elle réduit le recours aux soins de santé et donc le coût de la maladie. Dans cette synthèse, nous présenterons ce qu'est la réhabilitation pulmonaire, ses indications et ses résultats, et la façon dont elle se déroule en ambulatoire. [less ▲]Detailed reference viewed: 216 (29 ULg)
Indacaterol (Onbrez Breezhaler) et broncho-pneumopathie chronique obstructive.
Corhay, Jean-Louis ; Louis, Renaud
in Revue Médicale de Liège (2011), 66(9), 498-502
Indacaterol is a novel ultra long-acting beta 2-agonist (ultra-LABA), given once-daily, developed for the treatment of Chronic Obstructive Pulmonary Disease (COPD). The clinical studies suggest that ... [more ▼]
Indacaterol is a novel ultra long-acting beta 2-agonist (ultra-LABA), given once-daily, developed for the treatment of Chronic Obstructive Pulmonary Disease (COPD). The clinical studies suggest that indacaterol produces a rapid (within 5 minutes) and sustained bronchodilation (at least 24 hours) in patients with COPD. It improves also several important parameters as lung function, the quality of life, symptoms, exercise capacity, resting and dynamic hyperinflation, and exacerbations, while being well tolerated. These outcomes justify its use in moderate to very severe COPD patients. This review will give a brief summary of recent clinical data on the indacaterol, its comparison with other pharmacological agents used in the treatment of COPD, and also some information about its use in routine. [less ▲]Detailed reference viewed: 58 (0 ULg)
La vignette diagnostique de l'etudiant. La dyspnee.
in Revue Médicale de Liège (2011), 66(9), 503-6
Dyspnea is an extremely common symptom in medicine and in cardio-pulmonary medicine in particular. In most of the cases dyspnea reflects an unbalance between the ventilatory demand and the possibility of ... [more ▼]
Dyspnea is an extremely common symptom in medicine and in cardio-pulmonary medicine in particular. In most of the cases dyspnea reflects an unbalance between the ventilatory demand and the possibility of the thoracic and lung mechanics. Through to a simple clinical case describing an early stage of lung fibrosis we review the main causes and the differential diagnoses of dyspnea, and provide means of grading it through validated assessment scales. [less ▲]Detailed reference viewed: 30 (4 ULg)
2B4 (CD244) is involved in eosinophil adhesion and chemotaxis, and its surface expression is increased in allergic rhinitis after challenge.
; HENKET, Monique ; Lefèbvre, Philippe et al
in International Journal of Immunopathology and Pharmacology (2011), 24(4), 949-60
A role for the subtypes of CD2 Ig superfamily receptors has been recently demonstrated in eosinophilic inflammation in experimental asthma and atopic asthmatics. We investigated the functions of 2B4 ... [more ▼]
A role for the subtypes of CD2 Ig superfamily receptors has been recently demonstrated in eosinophilic inflammation in experimental asthma and atopic asthmatics. We investigated the functions of 2B4 (CD244) molecules in eosinophil adhesion and chemotaxis, and correlated the results to the pathophysiology of allergic rhinitis (AR). Herein, we show that agonistic stimulation of 2B4 by C1.7, the anti-human 2B4 functional grade purified antibody, resulted in significant increase of eosinophils and eosinophil cell line (Eol-1 cells) adhesion to collagen type IV, and random migration. These functions were associated with tyrosine kinase phosphorylation of several protein residues of low molecular weight. Flow cytometry (FACS) experiments demonstrated that Eol-1 cells, normal peripheral blood eosinophils and eosinophils from AR patients, express surface 2B4 molecules. In vitro AR model demonstrated that the CC-chemokine receptor CCR3 stimulation by eotaxin induced significant increase in the expression of surface 2B4 in eosinophils and Eol-1 cells. Immunofluorescence confocal microscopy images showed that eotaxin induces also redistribution of 2B4 molecules towards the pseudopods in eosinophils and Eol-1 cells, changing their shape. Blocking of 2B4 molecules by the corresponding neutralizing antibody inhibited eotaxin induced Eol-1-adhesion, chemotaxis and the cytoskeleton changes. Pretreatment of Eol-1 cells with 1 microM genistein blocked eotaxin-induced Eol-1 adhesion, chemotaxis and 2B4 up-regulated expression. In vivo correlation demonstrated the expression of 2B4 molecules in eosinophils from AR patients to be significantly increased, after nasal provocation challenge. These results identify a novel role for 2B4 molecules in eosinophil functional migratory response and may point to a novel tyrosine kinase-mediated ligation between CCR3 receptor and 2B4 co-receptor in eosinophil chemotaxis. If so, then 2B4 molecules would be a novel target for therapeutic modalities in diseases characterized by eosinophilia such as AR. [less ▲]Detailed reference viewed: 14 (2 ULg)
Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease.
Moermans, Catherine ; HEINEN, Vincent ; NGUYEN DANG, Delphine 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 ▲]Detailed reference viewed: 48 (15 ULg)
Y a-t-il une place pour les β-bloquants dans les maladies pulmonaires obstructives ?
; FRUSCH, Nicolas ; DUYSINX, Bernard et al
in Revue Médicale de Liège (2011), 66(12), 619-623Detailed reference viewed: 27 (3 ULg)
Apport de la greffe pulmonaire dans les pathologies respiratoires terminales.
; DUYSINX, Bernard ; NGUYEN DANG, Delphine et al
in Revue Médicale de Liège (2011), 66(7-8), 434-9
Lung transplantation is an established treatment of pulmonary diseases at an advanced stage. The purpose of our study is to present the benefits, indications and complications of this surgical procedure ... [more ▼]
Lung transplantation is an established treatment of pulmonary diseases at an advanced stage. The purpose of our study is to present the benefits, indications and complications of this surgical procedure in the CHU of Liege. The cohort includes 14 patients transplanted between 2005 and 2009, and who were inserted in a pulmonary rehabilitation programme at the university hospital of Liege. The criteria of assessment are the values of respiratory function tests at rest and exercise, and quality of life. Inherent complications related to this type of surgical operation have been collected. We found a dramatic improvement in pulmonary function tests performed at rest both immediately after the transplantation and after 6 months. Likewise exercise capacity was already increased shortly after the transplantation and further improved 6 months later. As for health related quality of life, parameters that improved the most were dyspnoea and global quality of life, and the improvement was already maximal immediately after the transplantation. Our retrospective study confirms the data of the literature, namely an improvement of respiratory function, effort capacity and quality of life after lung transplantation. [less ▲]Detailed reference viewed: 29 (4 ULg)
L'image du mois. Geyser endobronchique secondaire a une fistule broncho-oesophagienne.
DUYSINX, Bernard ; HEINEN, Vincent ; FRUSCH, Nicolas et al
in Revue Médicale de Liège (2011), 66(10), 511-2Detailed reference viewed: 8 (2 ULg)
Beyond corticosteroids: future prospects in the management of inflammation in COPD.
; ; et al
in European Respiratory Review (2011), 20(121), 175-82
Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and ... [more ▼]
Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease-antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities. Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators. Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge. [less ▲]Detailed reference viewed: 9 (0 ULg)