[Which physical tests for which objectives in pulmonary rehabilitation?] / Quels tests physiques pour quels objectifs en réadaptation respiratoire ?

Chronic respiratory disease is a major cause of morbidity and mortality worldwide and an important cause of disability including a reduction of exercise, functional and muscle capacity contributing to a decreased quality of life. In the context of pulmonary rehabilitation, a thorough patient-centered outcome assessment, including not only measures of lung function, but also exercise functional and muscle capacity, is imperative for a comprehensive disease management. Assessment of these impairments and dysfunctions with appropriate and change-sensitive procedures is thus necessary for personalizing the physical interventions and assessing the short- and long-term effectiveness of the intervention. The clinician currently has a wide variety of tests and measurements available to assess the physical and functional capacity of people with chronic respiratory disease. The aim of this review is to provide a pragmatic synthesis of the physical, functional and muscle capacity tests most commonly used in pulmonary rehabilitation. Ultimately, it should help the clinician to identify the relevant evaluations according to the objectives of the patients but also according to the available resources, the setting of pulmonary rehabilitation and the specific qualities of each test.

Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française (summary).

Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.

Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française / Prise en charge des exacerbations de la bronchopneumopathie chronique obstructive (BPCO). Recommandations de la Société de pneumologie de langue française

Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.(AU)

La bronchopneumopathie chronique obstructive (BPCO) est la maladie respiratoire chronique dont le poids sur la santé publique est le plus grand par sa morbidité, sa mortalité et les dépenses de santé qu'elle induit. Pour les individus atteints, la BPCO est une source majeure de handicap du fait de la dyspnée, de la limitation d'activité, des exacerbations, du risque d'insuffisance respiratoire chronique et des manifestations extra-respiratoires qu'elle entraîne. Les précédentes recommandations de la Société de pneumologie de langue française (SPLF) sur la prise en charge des exacerbations BPCO date de 2003. Se fondant sur une méthodologie adaptée de GRADE, le présent document propose une actualisation de la question des exacerbations de BPCO en développant un argumentaire couvrant quatre champs d'investigation : (1) épidémiologie, (2) évaluation clinique, (3) prise en charge thérapeutique et (4) prévention. Les modalités spécifiques de la prise en charge hospitalière et ambulatoire y sont discutées, particulièrement les aspects relevant de l'évaluation de la sévérité de l'exacerbation et de la prise en charge pharmacologique.(AU)

[Survey on anaesthetic practices for electroconvulsivotherapy in French university hospitals]. / Anesthésie pour électroconvulsivothérapie: résultats d'une enquête dans les CHU.

OBJECTIVES: To evaluate the anaesthetic management of electroconvulsive therapy (ECT) in French university hospitals. STUDY DESIGN: National survey in university hospitals by mail. MATERIALS AND METHODS: An email was sent to heads of department of anaesthesiology in French university hospitals to identify a referent practitioner, which we then sent a computerized quiz. The questions were about the volume and organization of the activity, pre-, per- and post-anaesthetic management of patients undergoing ECT. RESULTS: Of the 33 sites performing ECT, 28 (85%) responded. The anaesthesia consultation was systematic at least 48 hours before the start of treatment but the preanaesthetic visit was performed in 32% of the centers. A routine electrocardiogram was performed in 89% of patients. In four centers (25%), neuromuscular blockade was not systematic. Propofol was the agent most widely used (82%) and etomidate and thiopental in 11% and 7% respectively. In two centers, practitioners did not report using oral protection. The psychiatrist was present in 71% of cases. The electroencephalogram was continuously recorded in 45% of the centers. CONCLUSION: The recommendations remain valid while old and may be updated. They are not always followed by the teams. Continuing medical education should be promoted to a better understanding of the factors interfering between anesthesia and ECT.

[Bronchopulmonary aspergillosis infections in the non-immunocompromised patient]. / Infections aspergillaires broncho-pulmonaires du sujet non immunodéprimé.

The definition of broncho-pulmonary aspergillosis infections in non-immunocompromised patients remains vague and a wide range of clinical, radiological and pathological entities have been described with a variety of names, i.e. simple aspergilloma, complex aspergilloma, semi-invasive aspergillosis, chronic necrotizing pulmonary aspergillosis, chronic cavitary and fibrosing pulmonary and pleural aspergillosis, pseudomembranous tracheobronchitis caused by Aspergillus, and invasive aspergillosis. However, these disease entities share common characteristics suggesting that they belong to the same group of pulmonary aspergillosis infectious disorders: 1- a specific diathesis responsible for the deterioration in local or systemic defenses against infection (alcohol, tobacco abuse, or diabetes); 2- an underlying bronchopulmonary disease responsible or not for the presence of a residual pleural or bronchopulmonary cavity (active tuberculosis or tuberculosis sequelae, bronchial dilatation, sarcoidosis, COPD); 3- generally, the prolonged use of low-dose oral or inhaled corticosteroids and 4- little or no vascular invasion, a granulomatous reaction and a low tendency for metastasis. There are no established treatment guidelines for broncho-pulmonary aspergillosis infection in non-immunocompromised patients, except for invasive aspergillosis. Bronchial artery embolization may stop hemoptysis in certain cases. Surgery is generally impossible because of impaired respiratory function or the severity of the comorbidity and when it is possible morbidity and mortality are very high. Numerous clinical cases and short retrospective series have reported the effect over time of the various antifungal agents available. Oral triazoles, i.e. itraconazole, and in particular voriconazole, appear to provide suitable treatment for broncho-pulmonary aspergillosis infections in non-immunocompromised patients.

[Malt lung lymphoma]. / Lymphome pulmonaire de type MALT: mise au point.

MALT lung lymphoma is a low-grade primarily B-cell lymphoma. Most cases develop in a pain free patient presenting a chronic alveolar opacity. In this review, we describe the clinical radiological and pathological features as well as the diagnostic approach to this pathological entity. Prognosis is excellent. Therapeutic options are discussed.

[Cardiorespiratory limits to the surgical treatment of lung cancer]. / Limites cardiorespiratoires à la chirurgie du cancer broncho-pulmonaire.

Cardiorespiratory co-morbidity is a predictive factor of post-surgical mortality and morbidity. In the case of lung cancer, the pre-therapeutic work-up must assess the post-surgical risks by integrating such co-morbidity. In view of this, predictive scores and decisional algorithms have been developed. However, such tools were developed and assessed only to predict post-surgical risks during the first or second month following resection. Till now, prediction of long term quality of candidates for pulmonary resection has not be studied, although the question has often been raised by the patient and the medical and surgical teams, notably in the case of cardiorespiratory limitation prior to the intervention. A study on the predictability of the quality of life at 6 months following pulmonary resection was conducted in the Tenon hospital in a cohort of 81 patients, candidates for resection, initially selected on an MMFR lesser than 80% of the reference. Out of the 43 patients who finally underwent resection and were analysed at 6 months, there were few predictive factors for the alteration in quality of life at 6 months following pulmonary resection, other than the extension of the surgical act. Conversely, this alteration did not significantly depend on the immediate post-surgical events and can be explained by the deterioration in respiratory function.

Upregulation of bronchioloalveolar carcinoma-derived C-X-C chemokines by tumor infiltrating inflammatory cells.

OBJECTIVE AND DESIGN: The presence of increased numbers of tumor-infiltrating neutrophils is associated with poorer outcome in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We evaluated the role of inflammatory environment on C-X-C chemokine tumor production. MATERIALS: Bronchoalveolar lavage from 31 consecutive patients with adenocarcinoma of the BAC subtype as well as tumor and normal pulmonary tissue samples. A549 BAC cell line. Peripheral blood mononuclear cells (PBMC), polymorphonuclear neutrophils (PMN) and alveolar macrophages (AM). METHODS: Elisa measurements and immunohistochemical studies of ENA-78, IL-8, IL-1beta and TNF-alpha. RNA isolation, reverse transcription, and PCR amplification of ENA-78 and IL-8. RESULTS: C-X-C peptides were expressed by tumor cells of all the tumor specimens tested. ENA-78 and IL-8 were also expressed by AM. To better understand the regulation of the C-X-C production, BAC cell line was cultured alone or with inflammatory cells. PBMC upregulated both tumor ENA-78 and IL-8 mRNA expression and protein release whereas AM only upregulated ENA-78 mRNA expression and protein release; PMN had no effect. Anti-human IL-1beta antibodies (ab) inhibited the A549 ENA-78 and IL-8 production stimulated by PBMC-CM. Anti-human TNF-alpha ab inhibited A549 ENA-78 production stimulated by AM-CM. IL-1beta and TNF-alpha were expressed in vivo by inflammatory cells, although TNF-alpha was also expressed by tumor cells. CONCLUSIONS: This work emphasizes the role of the host inflammatory response in promoting tumor growth in vivo.

Transforming growth factor-beta inhibits interleukin-10 synthesis by human monocytic cells.

Transforming growth factor-beta (TGF-beta1) enhances interleukin-10 (IL-10) synthesis by mouse monocytes/macrophages, suggesting a potential role of IL-10 in mediating some of the anti-inflammatory properties of TGF-beta1. Since differences exist between the transcriptional regulation of human and mouse IL-10, the studies reported here examined whether TGF-beta1 up-regulated IL-10 production by human monocytes/macrophages as well. Exposure of PMA-differentiated U-937 promonocytic cells to TGF-beta1 resulted in an unexpected, dose-dependent decrease in IL-10 production as assessed by specific ELISA. TGF-beta1 was effective when added at the time of the PMA stimulus or 6 hours after. In addition, TGF-beta1 suppressed induction of IL-10 by three different stimuli other than PMA. TGF-beta1 inhibition of IL-10 protein release was associated with proportional changes in IL-10 mRNA accumulation as assessed by quantitative kinetic ELISA PCR. This would result from a decrease in IL-10 gene transcription as TGF-beta1 did not affect IL-10 mRNA stability, and TGF-beta1 limited the luciferase activity in cells transfected with reporter gene constructs containing 1,308 bp of the 5' non-coding sequence of human IL-10 gene. Blocking tumour necrosis factor-alpha (TNF-alpha) with neutralizing anti-TNF-alpha antibody did not modify the response to TGF-beta1, indicating the involvement of TNF-alpha-independent mechanisms in the overall process. Thus, the present study provides the first evidence that TGF-beta1 prevents IL-10 production by human monocytic cells at a transcriptional level.

Cytokines and hormones with anti-inflammatory effects: new tools for therapeutic intervention.

The inflammation that is involved in the development of glomerulonephritis is tightly regulated by the expression of anti-inflammatory factors. These include circulating hormones, such as glucocorticoids, and mediators that are produced by intrinsic cells and infiltrating leucocytes. The present review focuses on these anti-inflammatory factors, summarizing in particular their activities in existing models of glomerulonephritis. In addition, experimental evidence is presented that anti-inflammatory mediators are able to increase glucocorticoid binding or signalling in target cells. These data help to explain the in-vivo efficacy of anti-inflammatory mediators, and offer a promising new avenue for therapeutic intervention.

Somatostatin increases glucocorticoid binding and signaling in macrophages by blocking the calpain-specific cleavage of Hsp 90.

Somatostatin has direct anti-inflammatory actions and participates in the anti-inflammatory actions of glucocorticoids, but the mechanisms underlying this regulation remain poorly understood. The objective of this study was to evaluate whether somatostatin increases glucocorticoid responsiveness by up-regulating glucocorticoid receptor (GR) expression and signaling. Somatostatin promoted a time- and dose-dependent increase in [(3)H]dexamethasone binding to RAW 264.7 macrophages. Cell exposure to 10 nM somatostatin for 18 h promoted a 2-fold increase in the number of GR sites per cell without significant modification of the affinity. Analysis of GR heterocomplex components demonstrated that somatostatin increased the level of heat shock protein (Hsp) 90, whereas the level of GR remained almost unchanged. The increase in Hsp 90 was associated with a decrease in the cleavage of its carboxyl-terminal domain. Evidence for the involvement of calpain inhibition in this process was obtained by the demonstration that 1) somatostatin induced a dose-dependent decrease in calpain activity and 2) calpain inhibitors, calpain inhibitor I and calpeptin, both abolished the cleavage of Hsp 90 and induced a dose-dependent increase in [(3)H]dexamethasone binding. Increases in glucocorticoid binding after somatostatin treatment were associated with similar increases in the ability of GR to transactivate a minimal promoter containing two glucocorticoid response elements (GRE) and to interfere with the activation of nuclear factor-kappaB (NF-kappaB). Thus, the present findings indicate that somatostatin increases glucocorticoid binding and signaling by limiting the calpain-specific cleavage of GR-associated Hsp 90. This mechanism may represent a novel target for intervention to increase glucocorticoid responsiveness.

[Severe acute asthma in the emergency room: amelioration of decreased peak flow rate is interpreted with difficulty]. / Asthme aigu grave aux urgences: l'amélioration du débit de pointe doit être interprété avec discernement.

We report a severe acute asthma case whose course was marked by persistent hypoxemia whereas proximal flows were normalized. This discordance reveals a ventilation/perfusion mismatch. This data suggests that care must be taken in interpreting the peak flow improvement during acute severe asthma management.

Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms.

Transforming growth factor (TGF)-beta1 is a growth factor involved in the mechanisms of lung repair and fibrosis that follow inflammatory processes. We sought to examine the link between the generation of reactive oxygen intermediates (ROI) or reactive nitrogen intermediates (RNI) by inflammatory cells and the expression of TGF-beta1 by alveolar epithelial cells. Exposure of the A549 lung epithelial cell line to either an ROI generating system (xanthine and xanthine oxidase) or an RNI donor (S-nitroso-N-acetyl-penicillamine [SNAP]) promoted a time- and dose-dependent increase in TGF-beta1 release, as measured by a specific enzyme-linked immunosorbent assay. At the peak, the levels of TGF-beta1 were twice the control values. The induction of TGF-beta1 release by ROI was blunted by catalase and unaffected by superoxide dismutase, indicating the involvement of hydrogen peroxide. The response was also blunted by 5, 6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), a specific RNA polymerase II inhibitor, and accompanied by a corresponding increase in TGF-beta1 messenger RNA, as measured by quantitative/competitive reverse transcription polymerase chain reaction, suggesting the involvement of transcriptional mechanisms and possibly other downstream mechanisms. In contrast, RNI-induced TGF-beta1 release was unaffected by DRB and blunted by the protein synthesis inhibitor cycloheximide, suggesting the involvement of translational and post-translational mechanisms. This response required cyclic guanosine monophosphate (cGMP)- mediated processes because (1) immunoreactive cGMP accumulated in the culture medium of SNAP-treated cells; (2) SNAP-induced TGF-beta1 release was blunted by KT 5823, an inhibitor of cGMP-dependent protein kinase; and (3) similar increase in TGF-beta1 release was obtained by cell exposure to membrane-permeable dibutyryl-cGMP or to atrial natriuretic factor, a known agonist of particulate guanylate cyclase. These data suggest that in vitro exposure of human alveolar epithelial cells to ROI and RNI enhances TGF-beta1 release through different mechanisms. In vivo, this control may constitute a molecular link between inflammatory and fibrotic processes.

[Inflammatory mechanisms of renal fibrosis: glomerulonephritis]. / Mécanismes inflammatoires de la fibrose rénale: les glomérulonéphrites.

Studies of glomerulonephritis models have shown that inflammatory reaction is responsible for the development of glomerulosclerosis and tubulo-interstitial sclerosis and, hence, for the progression to end stage renal failure. That macrophage accumulation and fibrosis extension are frequently not closely related events suggests that macrophages are not involved in progression process. Glomerular sclerosis is rather associated with the release of mediators from resident cells-mainly growth factors such as platelet-derived growth factor and transforming growth factor-beta--the synthesis and bioactivity of which are enhanced by inflammatory mediators. Tubulo-interstitial sclerosis is induced by inflammatory lesions of the glomerulus that lead to proteinuria. Indeed, reabsorption of proteins in proximal tubule triggers epithelial cells to release proinflammatory and prosclerotic mediators into the interstitium. New therapeutic approaches including gene transfer strategies are directed at suppressing the efficiency of such mediators.

Growth hormone and somatostatin in glomerular injury.

Among other neuropeptides and neurohormones, growth hormone (GH) and somatostatin (SRIF) have been shown to modulate the development of glomerular injury in various renal diseases. In particular, GH is implicated in the induction of glomerular hypertrophy and sclerosis in partial nephrectomy and diabetic nephropathy. While GH effects on glomerular hypertrophy are likely mediated by insulin-like growth factor I (IGF-I), GH effects on glomerular sclerosis are independent of IGF-I. Those effects rather require multiple signaling pathways functioning in series, e.g. angiotensin II binding preceding transforming growth factor beta (TGF-beta) release, or pro-inflammatory factor release preceding repair/scarring processes. In contrast with GH, SRIF administration prevents the development of glomerular lesions in experimental diabetes, partial nephrectomy and immune glomerulonephritis. Inhibitory effects of SRIF on glomerular hypotrophy may be through a decrease in GH secretion and/or IGF-I expression or through a direct blockade of glomerular cell proliferation. The mechanisms underlying the anti-inflammatory effects of SRIF are most likely a deactivation of inflammatory cells related in part to an upregulated response of these cells to glucocorticoids. Additional studies will be required to further define the role of GH and SRIF in the development of glomerular injury and, hence, to identify new targets for a therapeutic approach in glomerular diseases.

Reduction of tumour necrosis factor alpha expression and signalling in peripheral blood mononuclear cells from patients with thalassaemia or sickle cell anaemia upon treatment with desferrioxamine.

Recent evidence indicates that the rate of progression of the HIV-1 disease is significantly reduced in thalassaemia major patients upon treatment with high doses of desferrioxamine (DFX). The authors have previously demonstrated that in vitro exposure of mononuclear cells to DFX decreases the bioavailability of tumour necrosis factor alpha (TNF-alpha) which has a stimulatory effect on HIV-1 replication. In this study, therefore, TNF-alpha bioavailability from mononuclear cells isolated from 10 patients with thalassaemia or sickle cell anaemia given DFX as compared to 10 untreated subjects has been evaluated. Evidence is presented showing that DFX treatment reduces TNF-alpha bioavailability (P<0.05) by inhibiting its steady state (P<0.05) and by enhancing its inactivation through binding to soluble TNF-alpha receptor type II (P<0.05). We also show that DFX treatment limits the in vivo activation of NF-kappaB, a transcription factor involved in both TNF-alpha gene transcription and TNF-alpha signalling (P<0.005). We conclude that TNF-alpha bioavailability and signalling are impaired in patients upon DFX treatment. This mechanism may contribute to delayed progression of the HIV-1 infection in vivo.

[Interactions between glucocorticoids and anti-inflammatory peptides]. / Interactions entre glucocorticoïdes et peptides anti-inflammatoires.

Both pro- and anti-inflammatory mediators regulate the anti-inflammatory actions of glucocorticoids, in part by modifying the binding of glucocorticoids to specific receptors. For instance, somatostatin has been shown to increase glucocorticoid binding and signaling in macrophages. The mechanism of this regulation does not require an increased expression of glucocorticoid receptors but, rather, a stabilization of glucocorticoid receptor-associated heat shock protein 90. This is related to a decrease in calpain activity. Thus calpain inhibition may offer a new and exciting possibility for enhancing the anti-inflammatory efficiency of glucocorticoids.