Login to your account

Username *
Password *
Remember Me

Blog With Right Sidebar

    Vous êtes ici :  
  1. Accueil
  2. Blog With Right Sidebar

Long-acting fluticasone furoate has a superior pharmacological profile to fluticasone propionate in human respiratory cells.

Currently available glucocorticoids are relatively short acting and may be less effective in patients with chronic obstructive pulmonary disease (COPD) where high levels of oxidative stress are seen.

Here we show that a novel glucocorticoid, fluticasone furoate (FF), has a longer duration of action in several cell systems compared with fluticasone propionate (FP) and budesonide, and unlike FP, FF is resistant to oxidative stress. FF had similar or slightly higher potency to FP and was 2-9 fold more potent than budesonide, when assessed at 4h, in inhibiting inflammatory cytokine production in epithelial cell lines (BEAS2B, A549), primary bronchial epithelial cells and a monocytic cell line (U937). The potency of FF was sustained beyond 16h with or without washout compared with FP or budesonide, such that it showed a greater duration of action in this range of cellular assays. The activated YFP-conjugated glucocorticoid receptor was detectable in nuclei of FF treated BEAS2B cells for at least for 30h, and FF had a longer duration of action than FP in inhibiting activation of transcription factors such as NF-κB and AP-1. In addition, FF showed superior effects to FP in peripheral blood mononuclear cells from patients with COPD and also in U937 cells or primary bronchial epithelial cells under conditions of oxidative stress.

The longer duration of action and oxidative stress insensitivity of FF compared with FP has potential clinical implications for the control of inflammation in respiratory diseases, such as COPD.

Matrix Metalloproteases in COPD.

There is considerable evidence that matrix metalloproteases (MMPs) are up and/or downregulated in COPD, particularly in emphysema where they probably participate in proteolytic attack on the alveolar wall matrix. Recent data suggest that MMPs also have major roles in driving inflammation or shutting it down, as well as modifying the release of fibrogenic growth factors, processes that are important in the genesis of the various lesions of COPD.

In cigarette smoke-induced animal models of emphysema MMP-12 appears to play a consistent and important role, whereas the data for other MMPs are difficult to interpret. In human lungs evidence for a role for MMPs is more tenuous and there are numerous contradictions in the literature. Little is known about the effects of MMPs in small airway remodeling, smoke-induced pulmonary hypertension, and chronic bronchitis, but MMP-12 participates in experimental small airway modeling.

At this point the accumulated data suggest that selective inhibition of MMP-12 might be a viable therapy for emphysema and small airway remodeling but subtle differences in the functions of MMP-12 in animals and humans mandate caution with this approach. Whether inhibition of other MMPs might be useful is unclear.

Severity and Outcomes of hospitalised community-acquired pneumonia in COPD Patients.

Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with community acquired pneumonia (CAP).

We investigated the impact of COPD on outcomes of CAP patients.We prospectively studied the clinical presentation of 1379 patients admitted with CAP during a 4 year-period. A comparative analysis of disease severity and course was performed between 212 patients with COPD, as confirmed by spirometry, and 1167 non-COPD patients.

COPD patients (median FEV1=47.7±16.3 % predicted) were older and more likely received previous antibiotics (37.1% vs. 28.3%, p<0.01) than those without COPD. They presented with more severe respiratory failure, (Pa,O2/FIO2 (270.4 vs. 287.8, p<0.01) and more severe pneumonia (PSI, 118.3 vs. 108.5; p<0.001). However, COPD patients had less multilobar infiltration (44 (21%) vs. 349 (30%), p<0.01) and less pulmonary complications (24 [14%] vs. 241 [24%]; p<0.01). A total of 89 patients (6.5%) died within 30 days. COPD patients had not different 30-days mortality rate compared to non-COPD patients (9 patients [4.2%] vs. 81[7%], p=0.14).

Despite worse clinical presentation COPD patients had a similar mortality compared to non-COPD patients. Previous antibiotic treatment and the decreased incidence pulmonary complications in COPD may account for these findings.

Reconsidering sex-based stereotypes of COPD.

Chronic obstructive pulmonary disease (COPD) has historically been considered a disease of older, white, male smokers, as illustrated in Frank Netter's classic images of the 'pink puffer' and 'blue bloater'. However, women may be more susceptible to COPD than men, and the disease course may be reflective of that increased susceptibility.

From a review of epidemiological data of COPD, we found differences in the way men and women present with COPD symptoms, a bias in the way COPD symptoms are treated in men and women, and differences in susceptibility to airway obstruction based on age, sex, and smoking history.

These data show that classic stereotypes of COPD - including male predominance - should be abandoned, and that there are not two but multiple COPD phenotypes, which are characterised by differences between women and men in susceptibility, symptoms, and disease progression.

These differences impact on physician perception. Although further research into this concept is needed, the differences we found should prompt, in the short term, changes in the way (and in whom) COPD is evaluated, diagnosed, and treated; in the long term, these differences should prompt research into the prognosis of COPD based on sex differences.

[Pulmonary non-infectious diseases in common variable immunodeficiency].

Few studies have described pulmonary non-infectious diseases (PNID) in patients with common variable immunodeficiency (CVID). Indeed the most frequent complications in these patients are infectious.

The aim of our study is to analyze the characteristics of PNID in a retrospective study of patients with CVID of two pneumology departments in Paris (France), from 1990 to 2008. PNID was observed in 11 patients. Mean immunoglobulin serum level was 3.46g/L. The PNID observed were: arteriovenous pulmonary fistula: three; interstitial lung disease: three; asthma: two; mediastinal lymphadenopathy: four; emphysema: one; mesothelioma: one.

Our study outlines the broad spectrum of pulmonary manifestations related to CVID. Clinicians should be aware of the diagnosis of PNID even in patients without classic infectious manifestations.

Search

Search