Available online 13 December 2012
Publication year: 2012
Source:Revue des Maladies Respiratoires



La bronchiolite oblitérante (BO) postinfectieuse est caractérisée par des phénomènes inflammatoires et fibrosants des petites voies aériennes succédant à un épisode infectieux pulmonaire et évoluant vers l’oblitération plus ou moins complète. C’est une cause rare de bronchopathie chronique obstructive, probablement sous-estimée, notamment pour les formes peu étendues. Les formes cliniques diffèrent entre l’enfant et l’adulte. Chez l’enfant, l’adénovirus est le principal agent infectieux en cause, notamment les sérotypes 3,7 et 21 qui sont les plus virulents. Le polymorphisme clinique et radiologique est important avec un pronostic fonctionnel qui dépend de l’extension des lésions pulmonaires. Le diagnostic repose sur la confrontation des données anamnestiques, tomodensitométriques et fonctionnelles. Le traitement est symptomatique et les formes les plus sévères évoluant vers l’insuffisance respiratoire chronique. Chez l’adulte, la fréquence des lésions obstructives définitives est mal connue. Une atteinte parenchymateuse est souvent associée, réalisant un tableau de BO avec pneumonie en voie d’organisation. Cette association modifie la présentation clinique et l’aspect radiologique du tableau infectieux initial et pose souvent de difficile problème de prise en charge. Certains auteurs ont rapporté des cas cliniques avec efficacité présumée d’une corticothérapie systémique mais les données sont parcellaires. Post-infectious bronchiolitis obliterans (BO) is characterized by inflammatory and fibrotic lesions of small airways following a pulmonary infection and leading to some degree of airway obstruction. It represents a rare cause of chronic obstructive pulmonary disease, and is probably underestimated, especially when the lesions affect small areas of the lungs. The clinical features differ between children and adults. In children, adenovirus is the most frequently involved infectious agent, especially the more virulent serotypes 3, 7 and 21. The clinical and radiological signs vary widely and the functional outcome depends on the extent of the lung injury. The diagnosis is based on the medical history, the CT-scan and functional data. The treatment is symptomatic. The most severe forms may result in chronic respiratory insufficiency. In adults, the frequency of obstructive injuries of the small airways in the context of lung infection is unclear. Parenchymal lesions are often present, resulting in BO with organizing pneumonia. These lesions alter the clinical presentation and the radiographic features of the initial infectious disease and often prove difficult to diagnose and manage. Several authors have published clinical cases describing presumed efficacy of systemic corticosteroids but the data are scarce.

Background: Statins are lipid-lowering agents that also exhibit pleiotropic effects in decreasing oxidative stress and inflammation. There have been several published studies reporting the use of statins in the treatment of asthma patients, but their results are not consistent.
The aim of this study is to determine whether statins are beneficial for asthma administration, and explore the potential covariables that may affect their clinical effectiveness.
Methods: A systematic literature search was performed in PubMed, Embase and Cochrane Center Register of Controlled Trials from inception to September 2012. Randomized controlled trial (RCT), retrospective study and controlled clinical trial which reported the use of statins in the treatment of asthma patients were eligible. Quality evaluation was conducted for RCT using Jadad criteria.
Results: A total of 18 articles were included. In our study, we found no conclusive evidence to demonstrate that statins could enhance the lung function in asthmatics, although, they may reduce airway inflammation. Additionally, the results were not consistent in different studies with respect to symptoms, quality of life, maintenance medication, asthma hospitalization/emergency department (ED) visits.
Conclusions: Statins may reduce airway inflammation in asthmatics, without having a significant effect on lung function. Further large sample and multicenter clinical trials are needed to confirm this and to see if there are more responsive phenotypes of asthma.

Background: Increased pulmonary arterial vascular smooth muscle (PAVSM) cell proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PH). The long-acting beta2-adrenergic receptor (beta2AR) agonist formoterol, a racemate comprised of (R,R)- and (S,S)-enantiomers, is commonly used as a vasodilator in chronic obstructive pulmonary disease (COPD). PH, a common complication of COPD, increases patients' morbidity and reduces survival. Recent studies demonstrate that formoterol has anti-proliferative effects on airway smooth muscle cells and bronchial fibroblasts. The effects of formoterol and its enantiomers on PAVSM cell proliferation are not determined.
The goals of this study were to examine effects of racemic formoterol and its enantiomers on PAVSM cell proliferation as it relates to COPD-associated PH.
Methods: Basal, thrombin-, PDGF- and chronic hypoxia-induced proliferation of primary human PAVSM cells was examined by DNA synthesis analysis using BrdU incorporation assay. ERK1/2, mTORC1 and mTORC2 activation were determined by phosphorylation levels of ERK1/2, ribosomal protein S6 and Ser-473-Akt using immunoblot analysis.
Results: We found that (R,R) and racemic formoterol inhibited basal, thrombin- and chronic hypoxia-induced proliferation of human PAVSM cells while (S,S) formoterol had lesser inhibitory effect. The beta2AR blocker propranolol abrogated the growth inhibitory effect of formoterol. (R,R), but not (S,S) formoterol attenuated basal, thrombin- and chronic hypoxia-induced ERK1/2 phosphorylation, but had little effect on Akt and S6 phosphorylation levels. Formoterol and its enantiomers did not significantly affect PDGF-induced DNA synthesis and PDGF-dependent ERK1/2, S473-Akt and S6 phosphorylation in human PAVSM cells.
Conclusions: Formoterol inhibits basal, thrombin-, and chronic hypoxia-, but not PDGF-induced human PAVSM cell proliferation and ERK1/2, but has little effect on mTORC1 and mTORC2 signaling. Anti-proliferative effects of formoterol depend predominantly on its (R,R) enantiomer and require the binding with beta2AR. These data suggest that (R,R) formoterol may be considered as potential adjuvant therapy to inhibit PAVSM cell proliferation in COPD-associated PH.

Background: Prognostic assessment is important for the management of patients with acute pulmonary embolism (APE). Pulmonary Embolism Severity Index (PESI) and simple PESI (sPESI) are new emerged prognostic assessment tools for APE.
The aim of this meta-analysis is to assess the accuracy of the PESI and the sPESI to predict prognostic outcomes (all-cause and PE-related mortality, serious adverse events) in APE patients, and compare between these two PESIs.
Methods: MEDLINE and EMBASE database were searched up to June 2012 using the terms "Pulmonary Embolism Severity Index" and "pulmonary embolism". Summary odds ratio (OR) with 95% confidence intervals (CIs) for prognostic outcomes in low risk PESI versus high risk PESI were calculated. Summary receiver operating characteristic curve (SROC) used to estimate overall predicting accuracies of prognostic outcomes.
Results: Twenty-one studies were included in this meta-analysis. The results showed low-risk PESI was significantly associated with lower all-cause mortality (OR 0.13; 95% CI 0.12 to 0.15), PE-related mortality (OR 0.09; 95% CI 0.05 to 0.17) and serious adverse events (OR 0.34; 95% CI 0.29 to 0.41), with no homogeneity across studies. In sPESI subgroup, the OR of all-cause mortality, PE-related mortality, and serious adverse events was 0.10 (95% CI 0.08 to 0.14), 0.09 (95% CI 0.03 to 0.26) and 0.40 (95% CI 0.31 to 0.51), respectively; while in PESI subgroup, the OR was 0.14 (95% CI 0.13 to 0.16), 0.09 (95% CI 0.04 to 0.21), and 0.30 (95% CI 0.23 to 0.38), respectively. For accuracy analysis, the pooled sensitivity, the pooled specificity, and the overall weighted AUC for PESI predicting all-cause mortality was 0.909 (95% CI: 0.900 to 0.916), 0.411 (95% CI: 0.407 to 0.415), and 0.7853+/-0.0058, respectively; for PE-related mortality, it was 0.953 (95% CI: 0.913 to 0.978), 0.374 (95% CI: 0.360 to 0.388), and 0.8218+/-0.0349, respectively; for serious adverse events, it was 0.821 (95% CI: 0.795 to 0.845), 0.389 (95% CI: 0.384 to 0.394), and 0.6809+/-0.0208, respectively. In sPESI subgroup, the AUC for predicting all-cause mortality, PE-related mortality, and serious adverse events was 0.7920+/-0.0117, 0.8317+/-0.0547, and 0.6454+/-0.0197, respectively. In PESI subgroup, the AUC was 0.7856+/-0.0075, 0.8158+/-0.0451, and 0.6609+/-0.0252, respectively.
Conclusions: PESI has discriminative power to predict the short-term death and adverse outcome events in patients with acute pulmonary embolism, the PESI and the sPESI have similar accuracy, while sPESI is easier to use. However, the calibration for predicting prognosis can't be calculated from this meta-analysis, some prospective studies for accessing PESI predicting calibration can be recommended.