[Tuberculosis and healthcare workers: Risk reduction and disease prevention in health care settings]. / Tuberculose et personnel soignant : prévention du risque en milieu de soins.

Tuberculosis is a human disease caused by Mycobacteriumtuberculosis, and transmitted by airborne pathway. Documented cases of tuberculosis infection in healthcare workers have been reported in both developed and developing countries. Early recognition of potentially infectious cases, immediate implementation of airborne precautions and prompt medical treatment of cases, are required to lower the risk of disease transmission. Molecular biology techniques allow earlier diagnosis. In the event of non-compliance with airborne precautions, the investigation will further have to establish exhaustive lists of potentially exposed healthcare workers and patients, looking for cases of latent tuberculosis infections whose treatment should help avoid active tuberculosis disease.

[Mediastinal fat necrosis]. / Nécrose de la graisse médiastinale.

Epicardial fat necrosis is a rare cause of benign chest pain. Its physiopathological mechanism is unknown. Diagnosis is easily performed through radiological investigations that show a round opacity of fat density limited by a dense pseudo-capsule in the anterior mediastinum, close to the heart.

[Bronchial thermoplasty in the treatment of severe adult asthma]. / La thermoplastie bronchique dans le traitement de l'asthme sévère de l'adulte.

Bronchial thermoplasty is a recent endoscopic technique for the treatment of severe asthma. It is an innovative treatment whose clinical efficacy and safety are beginning to be better understood. Since this is a device-based treatment, the evaluation procedure of risks and benefits is different that for pharmaceutical products; safety aspects, regulatory requirements, study design and the assessment of the magnitude of effects may all be different. The mechanism of action and optimal patient selection need to be assessed further in rigorous clinical and scientific studies. This technique is in harmony with the development of personalised medicine in the 21st century. It should be developed further in response to the numerous challenges and needs not yet met in the management of severe asthma.

Beyond corticosteroids: future prospects in the management of inflammation in COPD.

Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease-antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities. Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators. Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.

Pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic "crazy paving" pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.

[COPD and inflammation: Statement from a French expert group. How to treat inflammation?]. / BPCO et inflammation : mise au point d'un groupe d'experts. Comment traiter l'inflammation ?

INTRODUCTION: Management of chronic obstructive pulmonary disease (COPD) has made considerable progress over the last 15 years, with the development of pulmonary rehabilitation, new molecules to facilitate smoking cessation, and several medical treatments. Many therapeutic needs, however, remain to be met. STATE OF THE ART: Several lines of research on inflammation and COPD are promising, and some will probably result in new treatments. These may target specific populations, identified by clinical phenotype or by biomarkers. The forthcoming arrival of iPDE-4s on the market illustrates how knowledge of inflammation and remodeling and of some of the underlying mechanisms finally, after many years' development, has broadened the range of treatments available to help improve patients' daily life and outcomes. PERSPECTIVES AND CONCLUSIONS: The availability of such treatments, however, does not mean that knowledge of the disease in the general population and among healthcare workers can be neglected. Early detection (at a stage when treatment can already be effective) and patient education which promotes therapeutic compliance and lasting lifestyle change need to be developed further.

[COPD and inflammation: statement from a French expert group. Phenotypes related to inflammation]. / BPCO et inflammation: mise au point d'un groupe d'experts. Les phénotypes en lien avec l'inflammation.

INTRODUCTION: The objective of the present article is to review available data on possible links between phenotypes and inflammatory profiles in patients with chronic obstructive pulmonary disease (COPD). BACKGROUND: Chronic bronchitis is associated with proximal bronchial inflammation and small airway inflammation with remodeling at the site of obstruction. CT scanning enables patients to be phenotyped according to the predominantly bronchial or emphysematous nature of the morphological abnormality. Exacerbations, in a context of persistently elevated baseline inflammation, are associated with increased inflammation and a poor prognosis. Long-term studies have correlated inflammatory markers (and anti-inflammatory drug effects) with dynamic hyperinflation, possibly confirming that inflammation promotes hyperinflation. The inflammatory cell count in the pulmonary arterial walls correlates with the severity of endothelial dysfunction. The risk of developing pulmonary hypertension would seem to increase with low-grade systemic inflammation. The role of low-grade systemic inflammation in COPD co-morbidities, and in nutritional and muscular involvement in particular, remains a matter of debate. Regular physical exercise may help reduce this inflammation. CONCLUSIONS: In COPD, many aspects of the clinical phenotype are related to inflammation. Better knowledge of these relationships could help optimize current and future treatments.

[Pneumocystis pneumonia in a patient treated with pemetrexed for non small cell lung cancer]. / Pneumocystose chez un patient traité par pemetrexed pour adénocarcinome pulmonaire.

INTRODUCTION: Pneumocystis pneumonia is a life-threatening infection in patients undergoing chemotherapy for solid malignancies. CASE REPORT: A 49-year-old man developed gradually increasing dyspnoea while receiving pemetrexed as a third line treatment for an adenocarcinoma of the lung. The diagnosis of pneumocystis pneumonia was based on ground-glass opacities on the thoracic CT scan and alveolar lavage revealing occasional cysts of Pneumocystis jiroveci in the context of recent lymphopenia developing during chemotherapy. Treatment with cotrimoxazole for three weeks was only partially successful due to progression of the tumour. CONCLUSIONS: Pneumocystis pneumonia should be considered in cancer patients receiving antifolate drugs and presenting with increasing dyspnoea. It is important to identify a high-risk population among patients undergoing chemotherapy because of the significant morbidity and mortality and in order to administer effective prophylactic agents.

Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmatics.

BACKGROUND: Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. OBJECTIVES: The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. METHODS: A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. RESULTS: At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of -78% and -57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. CONCLUSIONS: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma

Diffuse interstitial pneumonia and pulmonary hypertension: a novel manifestation of chronic granulomatous disease.

The present authors report the case of an adult with chronic granulomatous disease who developed an unusual lung fibrosis associated with severe pulmonary hypertension. Histological analysis of a lung biopsy showed a diffuse infiltration with pigmented macrophages without granulomas, which particularly involved the pulmonary arterial and venular walls. Clinical and histological findings were suggestive of pulmonary veno-occlusive disease. Such a clinical association has not been previously described in the literature and might be due to the persistent expression of gp91phox at a very low level. In conclusion, the present case report illustrates a novel manifestation of chronic granulomatous disease.

Rituximab therapy in autoimmune pulmonary alveolar proteinosis.

Idiopathic pulmonary alveolar proteinosis is presumed to be an autoimmune disorder that may lead to pulmonary insufficiency. However, steroids do not appear to be effective and the standard of therapy is whole-lung lavage. We report the first case of successful therapy with rituximab, which addresses the pathogenic mechanism of pulmonary alveolar proteinosis.

[Contribution of ATP-dependent potassium channels, nitric oxide and prostaglandins in increase of diaphgram arteriolar blood fow during diaphgram contraction]. / Contribution des canaux potassiques ATP-dépendant, du monoxyde d'azote et des prostaglandines dans l'augmentation du débit artériolaire lors de la contraction du diaphragme.

ATP-sensitive potassium (K(ATP)) channels and nitric oxide (NO) have been suggested to contribute in mediating active hyperemia in diaphragm. However, no data is available in the current literature concerning their comparative contributions to arteriolar dilation during muscle contraction. The aim of this study was therefore to examine, by video microscopy in rats, the effects of superfusing the muscle with Krebs solution alone (group C), or Krebs solution containing either glybenclamide (3mdeltaM, a blocker of K(ATP), group GLY), or Nwdelta-nitro-L-arginine (300 mdeltaM, a NO synthase inhibitor, group NNA), or mefenamic acid (50 mdeltaM, a prostaglandin synthesis inhibitor, group MA) on second and third order of diaphragm (A2 and A3 respectively) arteriolar dilation elicited by 3 min muscle stimulation (40 Hz, train duration: 300 milliseconds, 90 cycles per min). In group C, A2 diameters increased by 67.5 +/- 1.9% referring to baseline at the end of the stimulation. This increase was significantly reduced in groups GLY and NNA (16.7 +/- 2.5% and 47.3 +/- 2.2% respectively, p < 0.001 as compared to group C) and was more important in group GLY than in group NNA (p < 0.001). By contrast, no difference in post-contraction diameter was observed between groups C and MA. Similar results were observed in A3 vessels. These results indicate that K(ATP) are more important mediators of functional diaphragm arteriolar dilation in rat than NO, whereas prostaglandins are not involved in this phenomenon.

[Niemann-Pick disease type B identified following an episode of bronchopneumonia]. / Maladie de Niemann-Pick de type B révélée par une atteinte bronchopulmonaire.

Niemann Pick disease type B (NPD type B) is a rare autosomal recessive lipid storage disorder, characterized by a partial deficiency of sphingomyelinase. We report the case of an adult male patient affected by NPD type B and diagnosed at 39-years-of age. Pulmonary CT scan revealed a cranio-caudal gradient with nodular centrilobular ground glass opacities and thickening of the interlobular septa. Pathological examination of the bronchoalveolar lavage showed foamy alveolar macrophages and vacuolated bronchial epithelial cells on bronchial biopsy. Diagnostic confirmation was achieved by a decrease in cell lysosomal enzyme activity and by the presence of the homozygous DeltaR608 mutation in the acid sphingomyelinase gene (SMPD1).

Activation of somatostatin receptors attenuates pulmonary fibrosis.

BACKGROUND AND AIM: Somatostatin analogues may have antifibrotic properties in the lung. The aim of this study was to evaluate the expression of the five somatostatin receptors sst1 to sst5 in normal and fibrotic mouse lung and the action of SOM230 (pasireotide), a new somatostatin analogue with a long half-life, in bleomycin induced lung fibrosis and in human lung fibroblasts in vitro. METHODS: After intratracheal injection of bleomycin, C57Bl6 male mice received one daily subcutaneous injection of SOM230 or saline. The lungs were evaluated on days 3, 7 and 14 after administration of bleomycin. RESULTS: We found that all somatostatin receptors were expressed in the normal mouse lung. The sst2 receptor mRNA expression was increased after bleomycin. SOM230 improved mice survival (69% vs 44%; p = 0.024), reduced lung collagen content at day 14 and decreased lung collagen-1 mRNA at day 7. SOM230 reduced bronchoalveolar lavage inflammatory cell influx at day 3, decreased lung connective tissue growth factor mRNA and transforming growth factor (TGF) beta mRNA and increased lung hepatocyte growth factor and keratinocyte growth factor mRNA. The sst2 receptor was strongly expressed in the human lung (normal or fibrotic), particularly by fibroblasts. In vitro, SOM230 reduced BrdU incorporation by control human lung fibroblasts cultured under basal conditions or with TGFbeta, and reduced alpha-1 collagen-1 mRNA expression in TGFbeta stimulated fibroblasts. CONCLUSION: We conclude that SOM230 attenuates bleomycin induced pulmonary fibrosis in mice and human lung fibroblasts activation. This study points to a potential new approach for treating pulmonary fibrotic disorders.

[Respiratory manifestations during the course of Sjogren's syndrome]. / Manifestations respiratoires au cours du syndrome de Gougerot-Sjögren.

INTRODUCTION: Sjogren's syndrome is a common auto-immune disease. BACKGROUND: Clinically significant pulmonary involvement affects approximately 10% of patients and may be the first manifestation of the disease, putting the respiratory physician in a position to suspect and confirm the diagnosis. Besides interstitial lung disease and bronchial disorders, cough is a common symptom of the disease and particularly difficult to treat. Lung cysts and amyloid deposits, sometimes associated with lymphoma, have recently been described. The development of a primary pulmonary lymphoma, usually from MALT, is a major complication of the disease. VIEWPOINT: Characterisation of the pathophysiology of pulmonary involvement in Sjogren's syndrome and the institution of specific treatment merits the interest of the respiratory physician. CONCLUSION: The respiratory physician should consider the diagnosis of Sjogren's syndrome in many different clinico-pathological situations.

Association of lung function decline with the heme oxygenase-1 gene promoter microsatellite polymorphism in a general population sample. Results from the European Community Respiratory Health Survey (ECRHS), France.

Inducible heme oxygenase (HO-1) acts against oxidants that are thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD), characterised by impaired lung function. A (GT)(n) repeat polymorphism in the HO-1 gene promoter can modulate the gene transcription in response to oxidative stress. We hypothesised that this polymorphism could be associated with the level of lung function and decline in subjects exposed to oxidative aggression (smokers). We genotyped 749 French subjects (20-44 years, 50% men, 40% never smokers) examined in both 1992 and 2000 as part of the ECRHS. Lung function was assessed by forced expiratory volume in 1 second (FEV1) and FEV1/forced ventilatory capacity (FVC) ratio. We compared long (L) allele carriers ((GT)(n) > or =33 repeats for one or two alleles) to non-carriers. Cross sectionally, in 2000, L allele carriers showed lower FEV1/FVC than non-carriers. During the 8 year period, the mean annual FEV1 and FEV1/FVC declines were -30.9 (31.1) ml/year and -1.8 (6.1) U/year, respectively. FEV1/FVC decline was steeper in L allele carriers than in non-carriers (-2.6 (5.5) v -1.5 (6.4), p = 0.07). There was a strong interaction between the L allele and smoking. In 2000, the L allele was associated with lower FEV(1) and FEV(1)/FVC in heavy smokers (> or =20 cigarettes/day) only (p for interaction = 0.07 and 0.002 respectively). Baseline heavy smokers carrying the L allele showed the steepest FEV1 decline (-62.0 (29.5 ml/year) and the steepest FEV1/FVC decline (-8.8 (5.4 U/year) (p for interaction = 0.009 and 0.0006). These results suggest that a long (L) HO-1 gene promoter in heavy smokers is associated with susceptibility to develop airway obstruction.

Comparative impact of standard approach, FDG PET and FDG dual-head coincidence gamma camera imaging in preoperative staging of patients with non-small-cell lung cancer.

We prospectively compared the impact of the standard approach, of fluorodeoxyglucose positron emission tomography (FDG PET) and of FDG dual-head coincidence gamma camera imaging (DHC) in preoperative staging of patients with non-small-cell lung cancer (NSCLC). In addition to traditional staging, 42 patients were studied with a PET system and a DHC system. The number of lesions detected on DHC and on PET were compared independently of the proof of a tumoural invasion. Then, for the sub-group of lesions with the proof of a tumoural invasion, the sensitivity of the different imaging modalities was compared. Finally, stagings were compared with final staging established by histopathological findings (n=28), additional imaging modalities (n=4), clinical and traditional imaging follow-up over at least 4 months. DHC detected 105 of the 145 lesions considered as pathological on PET (73%, P=0.01), with a concurrence of 89% (NS) in lesions larger than 1.5 cm, and only 17% (P=0.03) in those smaller or equal to 1 cm. Traditional staging detected 87 of the 114 verified tumoural lesions (76%), PET 110/114 (96%, P=0.01 vs traditional staging), DHC 88/114 (77%, NS vs traditional staging, P=0.01 vs PET). PET correctly predicted the N stage in 39/42 (93%) patients, DHC in 38/42 (90%), and computed tomography in 32/42 (76%). PET correctly predicted the M stage in 42/42 (100%) patients, DHC in 41/42 (98%), and traditional staging in 38/42 (90%). Identical NM staging was obtained with DHC and PET in 38/42 (90%) patients. Compared to traditional NM staging, PET correctly up-staged 9/42 (21%) patients and down-staged 3/42 (7%), with one additional false N up-staging. DHC correctly up-staged 7/42 (17%) patients and down-staged 3/42 (7%), with one additional false N down-staging. PET correctly reclassified 4/42 (9.5%) patients from resectable to unresectable and incorrectly reclassified one. DHC correctly reclassified 3/42 (7%) patients without false therapeutic reclassification. Although DHC detected fewer lesions than PET, DHC is a possible alternative to PET since the impact on staging was high as compared with traditional staging and was very similar to that of PET.