[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.

[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.

[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.

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.

Proton nuclear magnetic resonance studies of Nepsilon-Me-His2-thyroliberin. An hyperactive analogue of thyroliberin (thyrotropin-releasing factor).

The 270 MHz Proton magnetic resonance spectra of N-epsilon-Me-His2-thyroliberin in solution in deuterium oxide and deuterated dimethylsulfoxide have been analyzed. All the spectral features (chemical shifts, coupling constants, temperature dependence of NH peptide resonances) clearly show that no significant conformational difference exists between thyroliberin and its analogue. Upon changing solvent from Me2SO-2H6 to 2H2O, both molecules undergo a conformational change which affects the carboxamide group and the backbone of the second residue.

Insulin-like growth factors and their binding proteins in pleural fluid.

We investigated the expression and potential regulatory role of insulin-like growth factors (IGFs) and their specific binding proteins (BPs) in tuberculous and nontuberculous pleuritis. By using a radioimmunoassay after acid gel filtration chromatography, we found that mean concentrations of IGF-I were 211.9 +/- 20.2 microg/l and 203.2 +/- 31.1 microg/l in pleural fluid of 14 patients with tuberculous pleuritis and 9 patients with malignant pleuritis respectively. These values were near those in serum of the same patients (221.3 +/- 19.5 microg/l and 204.6 +/- 21.0 microg/l respectively). By using a specific protein-binding assay, we found that mean concentrations of IGF-II were 345.3 +/- 61.0 microg/l and 167.6 +/- 22.7 microg/l in tuberculous and malignant pleural effusions respectively. These values were significantly lower than those in serum of the same patients (628.3 +/- 79.0 microg/l, P<0.025 and 532.0 +/- 85.9 microg/l, P<0.025 respectively). Because bioavailability and bioactivity of IGFs may be regulated by their binding to IGFBPs, we studied IGFBP patterns in the pleural fluid of 6 patients with tuberculous pleuritis. As assessed by Western ligand blotting the levels of IGFBP-1 and IGFBP-2 were increased whereas those of IGFBP-3 were decreased in pleural fluid in comparison with serum. The decrease in IGFPB-3 levels reflected increased proteolysis, as assessed by Western immunoblotting. In spite of this presence of IGFBPs, IGFs could be responsible for the local biosynthesis of 1.25-dihydroxyvitamin D (1,25-(OH)2D) since pleural fluid levels of both IGF-I and IGF-II significantly correlated with those of 1,25-(OH)2D. These results indicate that IGFs are detectable in pleural fluid and may contribute to control the activity of 25-hydroxyvitamin D-1alpha hydroxylase in tuberculous pleuritis.

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.

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.

[From pseudolymphomas to primary pulmonary lymphomas of MALT type]. / Des pseudolymphomes aux lymphomes primitifs pulmonaires de type MALT.

Primary lung lymphomas are uncommon and the use of immunohistochemical and molecular biological techniques have widely contributed to their understanding. Generally, they are of low grade malignancy and most develop from mucosa-associated lumphoid tissue (MALT). Cellular analyses of samples obtained routinely by endoscopy (transbronchial biopsy or bronchoalveolar lavage) will probably enable the clinician to avoid invasive diagnostic procedures, such as surgical lung biopsy. Treatment of limited forms is usually surgical. As to bilateral forms or those with lesions of other mucosae e.g. gut, the best therapeutic strategy remains to be defined.

[Primary pulmonary lymphoma]. / Lymphome pulmonaire primitif.

There are three distinct clinico-anatomical entities today covered by the definition of a primary clonal pulmonary lymphoid proliferation. These are pulmonary lymphomas of B cell phenotype, of low grade malignancy, B cell lymphomas of high grade malignancy and finally lymphomatoid granulomatosis whose clonal characteristic is sometimes difficult to confirm. This general review aims to specify the pathophysiological, diagnostic, prognostic and therapeutic aspects of these different types. Low grade B cell lymphoma is the most common pulmonary lymphoma. Their development depends on mucosa associated lymphoid tissue. They are most often indolent and present as a chronic alveolar opacity. Their prognosis is excellent and the modalities of treatment are discussed (no therapy, surgery or monochemotherapy). High grade B cell pulmonary lymphomas are much rarer and may result from the transformation of a low grade lymphoma or arise in a particular situation such as imunodepression. Their prognosis is poor and the therapeutic possibilities depend most often on the underlying disease. The presence of lymphomatoid granulomatosis in this group of pulmonary lymphomas is debatable. The demonstration of a clonal character of this proliferation is practically never obtained and there is often extra pulmonary disease. The prognosis of this type of illness is extremely variable because certain studies have shown a cure using corticosteroids and cyclophosphamide whilst others have found that the disease is always fatal in spite of using strong polychemotherapy.

[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.

[Low extracellular pH has a role in the induction of NO synthase type 2 in macrophages]. / La baisse du pH extracellulaire participe à i'induction de la NO synthase de type 2 dans les macrophages.

Stimulation of macrophages with endotoxin and/or cytokines is responsible for the expression of the inducible isoform of nitric oxide synthase (iNOS). Because macrophages are exposed to low pH within the microenvironment of inflammatory lesions, the potential role of low pH as an additional regulator of iNOS was investigated. Substitution of the culture medium of rat peritoneal macrophages at pH 7.4 with medium at pH 7.0 upregulated iNOS activity, as reflected by a 2.5-fold increase in nitrite accumulation. The increase in iNOS activity was associated with a similar increase in iNOS mRNA expression. Low environmental pH-induced iNOS gene expression involved the activation of nuclear factor-kappa B (NF-kappa B) transcription factor since [1] exposure of macrophages to low environmental pH increased NF-kappa B binding activity in the nucleus, and [2] treatment of macrophages with pyrrolidine dithiocarbamate or n-acetyl-leucinyl-norleucinal, two drugs preventing NF-kappa B translocation to the nucleus, canceled low pH-induced nitrite accumulation. The overall mechanism required the synthesis of tumor necrosis factor-alpha (TNF-alpha). Indeed, [1] elevated TNF-alpha bioactivity was observed in the medium of macrophages exposed to pH 7.0, and [2] incubation of macrophages with a neutralizing anti-TNF-alpha antibody impaired both NF-kappa B activation and nitrite accumulation in response to acid challenge. In summary, exposure of macrophages to acidic microenvironment in inflammatory lesions leads to the upregulation of iNOS activity through the activation of NF-kappa B.

[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.

[Pulmonary hypertension: a rare complication of hepatic cirrhosis]. / Hypertension artérielle pulmonaire: une complication rare de la cirrhose hépatique.

Pulmonary hypertension is a rare pulmonary complication of chronic hepatic diseases. Anatomopathologic and clinic data are very similar to primary pulmonary hypertension. Although the lesions of arteriopathy are more related to portal hypertension than to hepatic lesions, the physiopathology of this morbid association is unknown.

[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.

[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.