[Assessment of recent weight history before instituting continuous positive airways pressure in a cohort of patients with severe obstructive sleep apnoea/hypopnea syndrome]. / Histoire pondérale récente, avant l'institution de la pression positive continue, dans une cohorte de patients ayant un syndrome d'apnées-hypopnées obstructives du sommeil sévère.

OBJECTIVES: The aim of this study is to evaluate the recent weight history in patients with the obstructive sleep apnoea/hypopnoea syndrome (OSAHS) needing treatment with continuous positive airways pressure (CPAP). PATIENTS AND METHODS: Over a period of 18 months, a self-administered questionnaire concerning recent weight history was given to patients during the installation of CPAP. RESULTS: The study population consisted of 1337 patients. An increase in weight of at least 5% over the 5 years preceding the institution of CPAP was found in 44% of patients. This increase was moderate (5-10%), important (10-20%) and very important (>20%) in respectively 12.3%, 16.1% and 15.6% of patients. The patients with important or very important weight gain differed from those whose weight remained steady in a higher percentage of women, young people, and patients with a higher prevalence of obesity, persistent smoking, a history of venous thromboembolism and treatment with anti-depressants. CONCLUSION: A recent increase in weight is frequently seen in severe OSAHS and is associated with some clinical characteristics.

[Mature mediastinal teratoma and sarcoid-like granulomatosis]. / Tératome mature médiastinal et granulomatose sarcoid-like.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disorder. However, when epithelioid cell granulomata are found in association with malignancy, they could correspond to a sarcoid reaction. CASE REPORT: We report the case of a young woman with mediastinal lymphadenopathy containing non-caseating granulomata. She also had a mass in the anterior mediastinum which proved, on surgical resection, to be an intrathymic mature teratoma. CONCLUSION: An association between a sarcoid-like reaction and testicular germ cell tumours has been described in literature. Our observation of a sarcoid reaction associated with a teratoma could be due to a hypersensitivity reaction to antigen released by the tumour.

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.

[Comorbidities in COPD: a new challenge in clinical practice]. / Les comorbidités dans la BPCO : un nouvel enjeu en pratique clinique.

Today it is a recognised fact that chronic obstructive pulmonary disease (COPD) is a real systemic disease that is respiratory-based. Recently, the focus has been on the importance of the comorbidities that are associated with COPD, such as all the cardiovascular diseases, lung cancer, diabetes, metabolic syndrome, peripheral muscular dysfunction, depression, anxiety, osteoporosis and anaemia, etc. These comorbidities constitute a new medical and therapeutic challenge with regard to COPD; their high frequency and considerable impact on the quality of life and the prognosis for survival of the patients make them a key element. The aims of this focus are to present the spectrum and prevalence of comorbidities in COPD, to obtain an objective view as to why and how these comorbidities should be systematically assessed and treated in patients, and subsequently to discuss the impact of this new data in clinical practice and in research. This recent data is another positive step in understanding the disease, optimising the diagnosis, and assessing and caring for COPD patients.

[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.

[Paraneoplastic sclerodermiform syndrome]. / Syndrome sclérodermiforme paranéoplasique.

INTRODUCTION: Despite the known association between scleroderma and cancer, the current systemic sclerosis classifications do not clearly identify paraneoplastic sclerodermiform syndrome or sclerodermiform syndrome secondary to cancer treatments. CASE REPORT: A 56 year old man was hospitalized for severe Raynaud's phenomenon with bilateral digital necrosis and otherwise good health status. X-rays did not show any subcutaneous calcification. Levels of serum antinuclear antibodies were high but anticentromere and anti-topoisomerase 1 antibodies were negative. Chest X-ray and CT-scan identified an irregular opacity in the right upper lobe with enlarged mediastinal lymph nodes. A diagnosis of bronchial adenocarcinoma was made following mediastinoscopy and the patient was treated with neo-adjuvant chemotherapy and lobectomy. After two cycles of treatment, his skin lesions had almost disappeared. CONCLUSION: The presence of a sclerodermiform syndrome may suggest the existence of an underlying neoplasm. In this case report, the skin lesions disappeared quickly after antineoplastic treatment. We suggest that sclerodermiform syndrome be included in the systemic sclerosis classification.

[Characteristics of the patients included in the French cohort of patients with emphysema caused by alpha-1 antitrypsin deficiency]. / Caractéristiques des patients inclus dans la cohorte française de patients emphysémateux déficitaires en alpha-1 antitrypsine.

INTRODUCTION: Alpha-1 antitrypsin deficiency is associated with the occurrence of pulmonary emphysema. The aim of this study is to describe the characteristics of patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema. METHODS: We describe a prospective cohort study including adult patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema confirmed by CT scan living in France. Patients' clinical and functional characteristics, quality of life measures and management were recorded every 6 months during a five-year period. RESULTS: 201 patients were included from 56 centres between 2005 and 2008. The characteristics of 110 patients have been analysed. Mean age was 50 years (SD:11.8), 62.7% were males, 90% were tobacco smokers. The main functional results (% predicted) were: FEV1: 42.8 (19.6), CPT: 128.3 (21.7), CRF: 167.0 (46.0), 6 minute walking distance (meters): 413 (130). 51 (46.4%) patients received augmentation therapy. Augmentation therapy was administered weekly (37.5%), twice a month (35.4%) or monthly (25.5%). Study centre was the only factor associated with the likelihood to received augmentation therapy. CONCLUSIONS: The clinical and functional characteristics as well as management of these patients varied markedly. There is a need for a standardization of the management of patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema.

[Non-invasive ventilation of elderly patients in the intensive care unit]. / Ventilation non invasive des patients âgés en réanimation.

INTRODUCTION: An increasing number of elderly patients, with acute respiratory failure (ARF) due to e.g. COPD exacerbation or cardiac failure, are being referred to intensive care units for mechanical ventilation. STATE OF ART: NIV can be an effective ventilatory technique in ARF due to a variety of aetiologies. NIV has been shown to decrease endotracheal intubation rates, complication rates and median hospital length of stay. When managing acute-on-chronic respiratory failure, NIV is a first-line ventilatory technique, in the absence of criteria for immediate endotracheal intubation. The efficacy of NIV depends on the expertise of the medical and nursing staff (including physiotherapists) and should always be performed in an appropriate setting. There are very few data about NIV in the elderly but studies, which included patients over 75 years, did not identify different outcomes for this age group. PERSPECTIVES: Future clinical studies on NIV should allow us to better understand which patients will benefit the most from the technique. Certain specific settings in elderly populations, such as in palliative care or when an "non intubation order" has been given by the patient, his family or the medical/nursing staff, are under evaluation. CONCLUSIONS: NIV is effective and well tolerated and it has become a key ventilatory technique in the management of ARF, particularly for elderly patients.

[Obstructive sleep apnea syndrome: medical treatment]. / Syndrome d'apnées obstructives du sommeil: traitement médical.

Medical management of patients with obstructive sleep apnea syndrome (OSAS) implies a multidisciplinary organization. Dietary advice is always needed because the great majority of these patients are significantly overweight. Drinking alcoholic beverages before bedtime and smoking must be advised against. Re-learning good sleeping habits is also necessary for certain patients with a chronic disorder. In patients with a mild to moderate OSAS, or whose diagnostic tracing demonstrates position-related respiratory events, it may be useful to avoid dorsal decubitus when sleeping. Sedatives should of course be totally avoided. Drug treatment for OSAS has generally been disappointing, but new serotoninergic receptor antagonists offer new possibilities. Medical management of associated conditions such as hypothyroidism must also be an integral part of the long term treatment of OSAS. The gold standard treatment remains continuous nocturnal positive pressure ventilation with proven efficacy largely demonstrated in several controlled trials showing often spectacular response within days. Prescription is guided by the intensity of the clinical diurnal and nocturnal symptoms, better results being obtained in patients with a high index of respiratory events. For patients with mild to moderate disease (index < 30) or for patients with severe disease who do not tolerate positive pressure ventilation, surgery or a mandibular advancement device should be considered.

Noninvasive ventilation in chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis.

Although long-term oxygen therapy (LTOT) improves survival, it has little effect on hypoventilation and other outcomes in patients with hypercapnic respiratory failure due to chronic obstructive pulmonary disease (COPD). Recent studies have shown that the use of noninvasive positive-pressure ventilation, when used in combination with LTOT in selected stable COPD patients, controls hypoventilation and improves daytime arterial blood gases, sleep quality, health status and may have a benefit in reducing exacerbation frequency and severity. Patients who show the greatest reduction in overnight carbon dioxide tension in arterial blood with ventilation are most likely to benefit from long-term ventilatory support. Some benefits have also been shown in patients with chronic respiratory failure due to bronchiectasis and cystic fibrosis, though survival is inferior in this patient group. As most studies of noninvasive positive-pressure ventilation in chronic obstructive pulmonary disease have been relatively short term, large multicentre studies with survival, exacerbations and hospital admissions as the primary end points are required to evaluate longer term effects.

[Mediastinal teratoma with recurrent encysted pleural effusion]. / Tératome médiastinal avec épanchement pleural enkysté récidivant.

A 25 year old man with no previous history was admitted for a recurrent right sided encysted pleural effusion. Thoracocentesis revealed an exudative lipase-rich-fluid. Because of the persistence of abundant pleural fluid after several thoracocentesis a diagnostic mediastinotomy was performed. This revealed a necrotic cystic mediastinal tumor composed of well differentiated pancreatic tissue, nervous tissue, digestive and respiratory glands, and a dermoid mass with hair and sebacious glands. This led to a diagnosis of benign, mature mediastinal teratoma. We suggest that the chronic pleural effusion was maintained by a fistula from the tumour into the pleural cavity and the secretion of proteolytic enzymes by the well-differentiated pancreatic tissue.

Rapid onset of bronchodilation in COPD: a placebo-controlled study comparing formoterol (Foradil Aerolizer) with salbutamol (Ventodisk).

Formoterol fumarate is a beta2-agonist bronchodilator that combines a fast onset of action with a long duration of action. Its fast onset of action is well documented in asthma but has not been directly compared with that of salbutamol in patients with chronic obstructive pulmonary disease (COPD). This randomized, double-blind, placebo-controlled study was conducted to assess the bronchodilatory effects over the first 3 h after inhalation of single doses of formoterol 24 microg delivered via the Aerolizer dry powder inhaler device (double-blind), or salbutamol 400 microg delivered by a Diskhaler dry powder inhaler (single-blind) in patients with COPD. A total of 24 patients with COPD were randomized [mean age 61.6 +/- 7.8 years, mean forced expiratory volume in 1 sec (FEV1) 1.38 +/- 0.32 l and 45.8 +/- 9.6% of predicted]. Inhalation of formoterol or salbutamol resulted in similar increases in FEV from 0 to 3 h post-dose. Both drugs produced similar bronchodilation by 5 min, which became almost maximal by 30 min. The primary efficacy variable, the area under the curve (AUC) of the FEV increase above predose baseline from 0 to 30 min (AUC(0-30 min)), demonstrated significant effects for formoterol (mean 5.89 +/- 4.67 l min(-1)), and salbutamol (mean 6.06 +/- 4.34 l min(-1)), which were not statistically different from each other but statistically significantly higher (P<0.0001) than that observed with placebo (-0.32 +/- 2.59 l min(-1)). In addition, both formoterol and salbutamol produced similar and rapid increases in forced vital capacity (FVC). In summary, this study confirms the rapid onset of action of formoterol and indicates that the onset of action of formoterol and salbutamol are similar in patients with COPD.

Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie study.

PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the treatment of previously untreated patients with metastatic small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine were standard premedication. Response to treatment was assessed every two cycles, and nonresponding patients were withdrawn from the trial to receive standard chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients were assessable for toxicity and response, respectively. The overall response rate was 65%, with complete responses in three patients. Five patients had stable disease (11%) and 11 patients experienced progressive disease (24%). Median survival was 38 weeks, and median duration of response was 20 weeks. One-year survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1 and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in 6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.

[A misleading tumor image]. / Un tableau tumoral trompeur.

Inflammatory pseudotumors of the lung are uncommon benign lung tumors. Their tendency for local extension requires an exact histopathological diagnosis to rule out neoplastic proliferation. The case presented here highlights the clinical findings as well as the difficulties in making the diagnosis and the therapeutic uncertainties.

[Proteins of the inter-alpha trypsin inhibitor (ITI) family. A major role in the biology of the extracellular matrix]. / Les protéines de la famille de l'ITI (inter-alpha trypsine inhibiteur). Un rôle majeur dans la biologie de la matrice extra-cellulaire.

A glycoprotein with a high inhibitory activity against trypsin was isolated in 1961 from human plasma and named inter-alpha trypsin inhibitor (ITI). Since then, several other proteins that share antigenic and structural similarities with ITI have been identified and classified as members of the ITI protein family. These glycoproteins built up from different combinations of four polypeptides HC1, HC2, HC3 and bikunin are encoded by four genes H1, H2, H3, L on three chromosomes. Bikunin has two proteinase inhibitor domains and belongs to the Kunitz-type protease inhibitor family; it displays an inhibitory activity against trypsin, leukocyte elastase and plasmin. The heavy chains do not have any protease inhibitory properties but have the capacity to interact in vitro and in vivo with hyaluronic acid. This binding promotes the stability of the extra-cellular matrix. Consequently, the ITI protein family is suspected of playing a key role in the extra-cellular matrix biology. Isolation of free heavy chains in bronchial secretions and the recent emphasis about the bikunin role in tumoral invasion should enhance the interest about ITI protein family in the pathophysiology of chronic bronchopulmonary diseases or lung cancer progression.