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Romain Pauwels

Publications and source records attributed to Romain Pauwels.

12 recordsLinked to original sources
PubMed2005

Pulmonary dendritic cells.

Dendritic cells (DCs) are leukocytes that are emerging as chief orchestrators of immune responses. The crucial task of DCs is the continuous surveillance of antigen-exposed sites throughout the body, and their unique responsibility is to decide whether to present sampled antigen in an immunogenic or tolerogenic way. Any misstep can either lead to a flawed immune defense or to allergy, even autoimmunity. It comes as no surprise that the lungs become increasingly the subject of DC-related investigations, as they represent a vast interface between the body and the outer world. This constitutes an enormous challenge for the immune system: "firing up" immune responses inappropriately could have devastating results for the fragile gas exchange structures. Evidence accumulates that DCs play a pivotal role in maintaining the delicate balance between tolerance and active immune response in our respiratory system. The exponentially growing body of DC-related publications is a big challenge. This article aims to provide researchers and clinicians with an up-to-date view on DC biology and its relevance to pulmonary medicine. A developing trend in the field of DCs is the shift from fundamental immunologic research toward exciting clinical insights and applications. For the pulmonary clinician, this heralds the dawn of promising therapies in various domains such as infections, allergy, and cancer.

Chemokines↗
PubMed2005

Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5'monophosphate in asthmatic patients.

The efficacy and systemic effects of ciclesonide, a novel glucocorticosteroid, inhaled via pressurized metered-dose inhaler (pMDI) were compared with fluticasone propionate pMDI in 26 patients with asthma, using a randomized, double blind, placebo-controlled, double dummy, 6-period crossover study design. Treatments were placebo, ciclesonide 320 microg (ex-actuator dose) once daily (o.d.), ciclesonide 640 microg o.d., ciclesonide 640 microg twice daily (b.i.d.), fluticasone propionate 440 microg (ex-actuator dose) b.i.d., and fluticasone propionate 880 microg b.i.d. The primary variable was area under the plasma cortisol concentration-time curve over 24 h (plasma cortisol AUC(0-24), relative to placebo) derived from samples taken every 2 h, on the 9th day of treatment. Secondary variables were 24-h urinary cortisol excretion and PC20 for adenosine 5'-monophosphate (AMP) (relative to placebo and expressed in doubling concentrations). Ciclesonide did not affect 24-h cortisol secretion. Fluticasone propionate suppressed cortisol secretion as demonstrated by a decrease in plasma cortisol AUC(0-24), relative to placebo, by 29% (95% CI 15-41) and 59% (95% CI 51-66) with 440 and 880 microg b.i.d., respectively. PC20 more than doubled with each active treatment, but no statistically significant dose-response effect could be established. It was concluded that moderate to high doses of fluticasone propionate suppressed cortisol secretion, that ciclesonide did not suppress cortisol secretion, and that all active treatments decreased hyperresponsiveness to AMP.

Adenosine Monophosphate↗
PubMed2004

Accurate and simple discrimination of mouse pulmonary dendritic cell and macrophage populations by flow cytometry: methodology and new insights.

BACKGROUND: The need to accurately discriminate dendritic cells (DCs) and macrophages (Mphs) in mouse lungs is critical given important biological differences. However, a validated flow cytometry-based method is still lacking, resulting in much confusion between both cell types. METHODS: Single-cell suspensions freshly obtained from collagenase-digested lung tissue were stained with a CD11c-specific monoclonal antibody, detected using a PE-Cy5 or APC-conjugated secondary reagent. Cellular immunophenotype was simultaneously explored using a panel of PE-conjugated markers. The FL1 or FITC-detection channel was reserved for the assessment of autofluorescence. RESULTS: CD11c-bright cells were heterogeneous and displayed a bimodal distribution with regard to autofluorescence (AF). CD11c+/low-AF cells were lineage-negative and showed features compatible with myeloid DCs. This was confirmed by morphology, potent T-cell stimulatory function in a mixed-leukocyte reaction, surface expression of MHCII and costimulatory molecules, and further immunophenotypical criteria, including the expression of Mac-1 and absence of CD8alpha. In contrast, CD11c+/high-AF cells displayed the features of pulmonary Mphs, including typical Mph morphology, very weak induction of T-cell proliferation, low to absent expression of MHCII and costimulatory molecules, and very low levels of Mac-1 as well as F4/80. We also show that only CD11c+/high-AF cells strongly expressed the macrophage marker MOMA-2, while interestingly Mac-3 was expressed at high levels by CD11c+/high-AF and low-AF alike. CONCLUSIONS: This study shows that the combination of CD11c-expression and autofluorescence is necessary and sufficient to accurately separate DCs from macrophage subpopulations in mouse lungs.

Animals↗
PubMed2004

Gender does not influence the response to the combination of salmeterol and fluticasone propionate in COPD.

The prevalence of chronic obstructive pulmonary disease (COPD) in women is increasing worldwide. Women may have greater susceptibility to COPD progression than men, and differences in efficacy and safety of respiratory medications by gender are largely unexplored. We aimed to determine whether the response to treatment in women with COPD differed from men in a large, 1-year double-blind trial ('TRISTAN'). In a sensitivity analysis, we compared 539 male and 180 female COPD patients, who were randomized to the saLmeterol/fluticasone combination 50/500mcg bid or placebo for 12 months. Combination therapy improved pre-treatment FEV1 significantly more than placebo in women by 152 ml (95% confidence interval 95-208) and in men by 127 ml (94-159). Similarly, a reduction in COPD exacerbation rates of 31% in women (9-48%) and of 23% in men (8-35%) was observed. Combination therapy reduced COPD exacerbations requiring treatment with oral corticosteroids by 36% in women and by 41% in men. Finally, combination treatment produced a better improvement in health status than placebo with a decrease in the SGRQ scores in women by -2.3 (-4.6 - 0.1) and in men by -2.1 (-3.5 to -0.8). No gender interaction was found for any outcome. Treatments were well tolerated with no difference in the frequency of adverse events in women and men. In this trial, therapy with the salmeterol/fluticasone combination produced significant improvements compared to placebo on all main endpoints and the magnitude of these improvements was similar for both men and women.

Adrenergic beta-Agonists↗
PubMed2003

Airway IgG counteracts specific and bystander allergen-triggered pulmonary inflammation by a mechanism dependent on Fc gamma R and IFN-gamma.

Besides IgE, the Ab isotype that gives rise to sensitization and allergic asthma, the immune response to common inhalant allergens also includes IgG. Increased serum titers of allergen-specific IgG, induced spontaneously or by allergen vaccination, have been implicated in protection against asthma. To verify the interference of topical IgG with the allergen-triggered eosinophilic airway inflammation that underlies asthma, sensitized mice were treated by intranasal instillation of specific IgG, followed by allergen challenge. This treatment strongly reduced eosinophilic inflammation and goblet cell metaplasia, and increased Th1 reactivity and IFN-gamma levels in bronchoalveolar lavage fluid. In contrast, inflammatory responses were unaffected in IFN-gamma-deficient mice or when applying F(ab')(2). Although dependent on specific allergen-IgG interaction, inflammation triggered by bystander allergens was similarly repressed. Perseverance of inflammation repression, apparent after secondary allergen challenge, and increased allergen capture by alveolar macrophages further characterized the consequences of topical IgG application. These results assign a novel protective function to anti-allergen IgG namely at the local level interference with the inflammatory cascade, resulting in repression of allergic inflammation through an FcgammaR- and IFN-gamma-dependent mechanism. Furthermore, these results provide a basis for topical immunotherapy of asthma by direct delivery of anti-allergen IgG to the airways.

Administration, Intranasal↗
PubMed2003

Matrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma.

Dendritic cells (DCs) appear to be strategically implicated in allergic diseases, including asthma. Matrix metalloproteinase (MMP)-9 mediates transmigration of inflammatory leukocytes across basement membranes. This study investigated the role of MMP-9 in airway DC trafficking during allergen-induced airway inflammation. MMP-9 gene deletion affected the trafficking of pulmonary DCs in a specific way: only the inflammatory transmigration of DCs into the airway lumen was impaired, whereas DC-mediated transport of airway Ag to the thoracic lymph nodes remained unaffected. In parallel, the local production of the Th2-attracting chemokine CC chemokine ligand 17/thymus and activation-regulated chemokine, which was highly concentrated in purified lung DCs, fell short in the airways of allergen-exposed MMP-9(-/-) mice. This was accompanied by markedly reduced peribronchial eosinophilic infiltrates and impaired allergen-specific IgE production. We conclude that the specific absence of MMP-9 activity inhibits the development of allergic airway inflammation by impairing the recruitment of DCs into the airways and the local production of DC-derived proallergic chemokines.

Allergens↗
PubMed2003

Accelerated airway dendritic cell maturation, trafficking, and elimination in a mouse model of asthma.

Pulmonary dendritic cells (DC) can induce both tolerogenic as well as inflammatory immune responses in the lung. Conversely, little is known about the impact of ongoing airway inflammation on pulmonary DC biology. In noninflammatory conditions, expression of T cell costimulatory molecules on mouse airway DCs is low and only upregulated after homing into draining thoracic lymph nodes. In this study, we reveal that ongoing allergic airway inflammation induces a premature upregulation of the T cell costimulatory molecules CD40, B7-2 and intercellular adhesion molecule 1 on DCs still present in the airways. In contrast, high surface expression of inducible costimulator ligand, involved in respiratory tolerance induction is restricted to DCs from noninflamed lungs. In addition, during inflammation the migratory flux of allergen-transporting airway DCs toward draining thoracic nodes increases both in amplitude as well as in speed. Remarkably, migratory DCs from inflamed airways are short-lived in the draining lymph nodes, a finding that is temporally associated with a marked loss of the antiapoptotic protein Bcl-2 in these cells. This study demonstrates the profound effects of ongoing allergen-driven airway inflammation on the dynamics of pulmonary DC physiology, a knowledge that could be exploited in the development of novel DC-based immunotherapies.

Allergens↗
PubMed2003

Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial.

BACKGROUND: Inhaled long-acting beta2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone. METHODS: 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 microg salmeterol twice daily (n=372), 500 microg fluticasone twice daily (n=374), 50 microg salmeterol and 500 microg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6h and from study medication for at least 12h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol. FINDINGS: All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105-161, p<0.0001), salmeterol (73 mL, 46-101, p<0.0001), or fluticasone alone (95 mL, 67-122, p<0.0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration. INTERPRETATION: Because inhaled long-acting beta2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.

Adrenergic beta-Agonists↗
PubMed2002

Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial.

Leukotriene antagonists block the proinflammatory actions of leukotrienes (LT) and have been introduced as new treatments for asthma. Conventional therapy with glucocorticosteroids does not inhibit the biosynthesis of leukotrienes. We therefore tested whether addition of the leukotriene receptor antagonist montelukast was of therapeutic benefit in a group of aspirin-intolerant patients with asthma of whom 90% already were treated with moderate to high doses of glucocorticosteroids. Under double-blind conditions, 80 aspirin-intolerant patients with asthma were randomized to receive 4 wk oral treatment of either 10 mg of montelukast or placebo once daily at bedtime. Pulmonary function was measured as forced expiratory volume in 1 s (FEV(1)) once a week in the clinic and daily as morning and evening peak expiratory flow rate (PEFR). Asthma symptoms and use of rescue bronchodilator were also recorded daily. Asthma specific quality of life (QoL) was assessed before and after the treatments. The group receiving montelukast showed a remarkable improvement of their asthma, whereas the group given placebo showed no change. Thus, from equal baseline values, the mean difference between the groups over the 4-wk treatment period was 10.2% for FEV(1) and 28.0 L for morning PEFR (p for both < 0.001). The improved pulmonary function in the group receiving montelukast occurred at the same time as 27% less bronchodilator was used (p < 0.05), and it was associated with fewer asthma symptoms than in the group given placebo, including 1.3 nights more of sleep per week and 54% fewer asthma exacerbations (p < 0.05). There was also an improvement in asthma-specific QoL (p < 0.05). The therapeutic response to montelukast was consistent across patients with different baseline characteristics and did not correlate with baseline urinary LTE(4). Addition of a leukotriene receptor antagonist such as montelukast improves asthma in aspirin-intolerant patients over and above what can be achieved by glucocorticosteroids.

Acetates↗
PubMed2002

Global Initiative for Chronic Obstructive Lung Diseases (GOLD).

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. In an effort to increase awareness of COPD and to develop consensus on scientific evidence for management and prevention of this disease, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) program was formed. A summary of the GOLD program is presented along with information about GOLD documents.

Asthma↗
PubMed2002

Asthma therapies and Churg-Strauss syndrome.

The pulmonary vasculitides are a group of rare but serious disorders that require early recognition, accurate diagnosis, and effective therapy. Churg-Strauss syndrome (CSS) is classified as small vessel vasculitis. Four different definitions for the diagnosis of CSS have been developed: (1) the pathologic criteria put forth by Churg and Strauss, (2) the criteria based on clinical grounds from Lanham and colleagues, (3) the criteria based on clinical grounds from the American College of Rheumatology, and (4) the criteria from the Chapel Hill Consensus Conference, which closely concur with the Churg and Strauss definition. It is apparent that cessation, diminution, or even a switch from low-dose systemic to inhaled corticosteroid therapy can precipitate the appearance of CSS. The term forme fruste has been used to indicate that the signs and symptoms of CSS were (inadvertently) suppressed by cortico-steroids. The clinical risk factors for CSS are moderately severe or severe asthma, chronic sinusitis, or reductions in systemic corticosteroid therapy. Differential diagnosis, treatment, and ongoing monitoring of CSS therapeutic responses are reviewed. The introduction of leukotriene modifiers and high-potency inhaled corticosteroids have allowed control of asthma symptoms, which results in avoidance or reduction in oral corticosteroid use. The advent of these agents has been associated with reports of CSS appearing in patients with asthma. The available data regarding the association of CSS and antiasthma agents are most consistent with the unmasking of a previously contained pathologic condition (forme-fruste CSS) or disease that progresses because systemic corticosteroids were avoided. Early recognition and immunosuppressive therapy are the keystones of successful treatment of this rare disorder.

Adrenal Cortex Hormones↗