[Pneumocystis jirovecii pneumonia in non-HIV infected patients: a study of 41 cases]. / Pneumocystose pulmonaire chez des patients immunodéprimés non infectés par le VIH : étude de 41 cas.

BACKGROUND: The increasing use of immunosuppressive and cytotoxic therapies leads to a growing number of opportunistic infections especially Pneumocystis jirovecii pneumonia (PCP). The purpose of our study was to describe the population involved, and to assess clinical, biological, and mortality data. METHODS: We collected retrospectively the whole medical file of all PCP cases diagnosed in non-HIV infected patients, in two French University Hospitals in the last decade (1999-2009). Diagnosis was made on standard coloration and/or immunofluorescence analysis of bronchoalveolar lavage fluid (BAL). RESULTS: Forty-one patients were included in the study, mean age 56 (±12.5) years, sex ratio 0.71 men/woman. Underlying diseases were as follow: 12 patients (29%) were renal transplant recipients, 13 (32%) were treated for solid cancers, and 16 (39%) suffered from various diseases (three allogenic bone-marrow transplantation, 11 hematological malignancies, one pulmonary transplantation, one vasculitis). Twelve patients died (i.e. 29%). Median lymphocyte count was 542/mm(3). More than 85% patients received corticosteroids at a median cumulative 6-month dose of 2700mg. Seven patients (17%) had a PCP prophylaxis. Clinical worsening at day 5 (P<0.003), poor control of the underlying disease (P<0.015), WHO performans status superior than 2 (P<0.025), high temperature (P<0.04), and high oxygen flow (P<0.042) were linked to a poor prognosis. DISCUSSION/CONCLUSION: The prognosis factors found are mostly linked to the patients' clinical severity. We would like to highlight: first, near to 30% mortality rate, secondly, a lack of prophylaxis in 34 patients, reflecting the difficulty to define PCP's risk in non HIV-infected patients.

[H1N1 (2009) influenza A infection in transplant recipient patients: a comparative study versus non-transplanted patients]. / Grippe A/H1N1 2009 chez des patients transplantés : étude comparative versus des patients non transplantés.

OBJECTIVE: To compare H1N1 (2009) influenza A infection characteristics between transplant recipient patients and non-transplanted patients. To assess the evolution of transplanted patients up to 6 months following infection. METHODS: Patients diagnosed with confirmed influenza A infection from three Parisian transplant centers between September 1st, 2009 and February 15th, 2010. Clinical symptoms, biological, and radiological findings, and management were analysed and retrospectively compared between transplanted (T) and non-transplanted patients (NT). The evolution was assessed by a follow-up questionnaire, CT results 1 to 3 months after influenza infection and FEV1 variation. RESULTS: Seventy patients were included. Thirteen patients had an allograft (lung: eight, kidney: four, stem cells: one): (1) hospitalization: 100% (13 out of 13) in group T, 54% (31 out of 57) in group NT (P=0.0013); (2) pneumonia: 62% (eight out of 13) in group T, 26% (eight out of 57) in group NT (P=0.004); (3) mortality rate among hospitalized patients: 7.7% (one out of 13) in the group T, 9.7% (three out of 57) in group NT (P=NS); (4) chest CT scan abnormalities remained in four lung transplanted patients; (5) a minimum 10% decrease in FEV1 was detected in four lung transplant recipients. CONCLUSION: Our results suggest that H1N1(2009) influenza A infection in transplant recipient patients compared to non-transplanted patients: (1) more often leads to hospitalization; (2) is more frequently associated with pneumonia; (3) is responsible for a persistent graft functional impairment in lung transplant recipients; (4) has a low mortality rate similar to admitted non-transplanted patients.

[Pulmonary non-infectious diseases in common variable immunodeficiency]. / Manifestations pulmonaires non infectieuses du déficit immunitaire commun variable.

Few studies have described pulmonary non-infectious diseases (PNID) in patients with common variable immunodeficiency (CVID). Indeed the most frequent complications in these patients are infectious. The aim of our study is to analyze the characteristics of PNID in a retrospective study of patients with CVID of two pneumology departments in Paris (France), from 1990 to 2008. PNID was observed in 11 patients. Mean immunoglobulin serum level was 3.46g/L. The PNID observed were: arteriovenous pulmonary fistula: three; interstitial lung disease: three; asthma: two; mediastinal lymphadenopathy: four; emphysema: one; mesothelioma: one. Our study outlines the broad spectrum of pulmonary manifestations related to CVID. Clinicians should be aware of the diagnosis of PNID even in patients without classic infectious manifestations.

[Lung surgery in haematological patients: useful? hazardous?]. / Chirurgie pulmonaire chez le malade d'hématologie : pourquoi ? Pour qui ?

Respiratory complications are frequent in haematological patients. Lung surgery, either for diagnosis or treatment, is considered useful but hazardous in these patients. We performed a reappraisal study of this purpose; retrospective study in a university centre, located in the Paris area, France. We analysed the entire records of all the haematological patients admitted in the Thoracic Surgery department from October 2001 to January 2009, among 400 haematological patients with pulmonary complications admitted to the Respiratory Diseases department. Seventeen patients (male: n=13, mean age 47 ± 15 years) underwent lung surgery. Underlying haematological disease was acute (n=7) or chronic (n=5) leukaemia, lymphoma (n=4), and eight have had stem cell transplantation. Thirteen patients had been exposed to a cytotoxic chemotherapy with known pulmonary toxicity. Respiratory diseases have been evolving for 112 days (10-663 days), and 14 patients received previously antibiotic and/or antifungal therapy. One patient was neutropenic and three had thrombopenia. Five patients underwent curative surgery for a residual pulmonary nodule after medical treatment of invasive aspergillosis, and 12 had a diagnostic procedure (open lung biopsy by video-assisted thoracoscopy [n=2]; thoracotomy [n=8]). Surgery permitted a final diagnosis in all 12 cases: non-specific infiltrative pneumonia (n=4), pulmonary graft versus host disease (n=3), granulomatous pneumocystosis (n=1), invasive aspergillosis (n=1), bronchial carcinoma (n=1), EBV-related lymphoproliferation (n=1), and tuberculosis (n=1). Therapeutic regimens were modified according to the surgical results in ten cases (84%). All patients were extubated at the end of surgery. Post-operative complications were: prolonged air leaks (n=3), pneumonia (n=1), parenchymal hematoma (n=1), acute coronary syndrome (n=1). Seven patients were admitted in the Intensive Care Unit, and five had non-invasive ventilation. Three patients died from respiratory failure: NSIP (n=2), pneumocystosis (n=1). Lung surgery for selected haematological patients has two indications: (1) curative surgery, for a residual pulmonary nodule after medical treatment of invasive aspergillosis; (2) diagnostic procedure, leading frequently to modifications of therapeutic regimens, with low rate of complications, in highly selected patients.

[Pulmonary arterial hypertension related to HIV: is inflammation related to IL-6 the cornerstone?]. / Hypertension artérielle pulmonaire liée à l'infection VIH : de la pression artérielle pulmonaire à l'interleukine-6.

Vascular diseases have become the leading cause of mortality in the population treated for HIV infection. Pulmonary arterial hypertension (PAH) related to HIV (PAH-HIV), the fourth cause of PAH in France, has the same histological pattern as other PAH from the group 1 of Dana Point classification. But, conversely to idiopathic PAH in the general population, PAH-HIV is particular by its high frequency in HIV-infected population. This raises the question for the role of inflammation in the PAH-HIV pathophysiology. Its constant occurrence over the decades, despite introduction of combination antiretroviral therapy (CAT), does not preclude the hypothesis of an involvement of inflammation in the genesis of PAH-HIV. Indeed, it is well known that normalization of CD4+ by the CAT does not mean no inflammation. Especially, it persists an increased and continuous production of IL-6, a main cytokine in the genesis of PAH lesions. This inflammation mainly involves the endothelin-1 pathway, which has an action on endothelium and macrophages, leading to high production of IL-6. Moreover, plasmatic level of IL-6 has a prognostic value in PAH-HIV, independently from conventional (functional or hemodynamic) parameters. The use of endothelin receptor antagonist permits major effect on IL-6 production and dramatic effect on PAH in so-called "bosentan responders".

[Obesity, poor prognostic factor in pandemic influenza A (H1N1) 2009: the role of adipokines in the modulation of respiratory defenses]. / L'obésité, facteur de mauvais pronostic au cours de l'épidémie de grippe A (H1N1) 2009 : rôle des adipokines dans la modulation des défenses respiratoires.

Pandemic influenza A (H1N1), which occurred during 2009, revealed some unexpected epidemiologic characteristics, notably the high number of obese subjects among the severe cases of influenza. Generally, obesity seems to be associated with a weakness when it comes to respiratory infections. This susceptibility may be the result of a concurrence of mechanical and hormonal factors due to the excess weight. Obesity leads to changes in the ventilatory mechanics and an increase in the metabolic load during exercise. It is associated with immune system changes. Adipokines, cytokines produced by adipocytes, including leptin, play a central role by modulating the activity of all the cells of the immune system. Finally, obesity is associated with an increased risk of thrombosis, which has an adverse effect on the prognosis of infections. All of these observations can explain that obesity has been a risk factor in serious cases of influenza.

[Bronchiolitis obliterans postallogeneic stem cell transplantation: what is new?]. / Bronchiolite oblitérante après allogreffe de cellules souches hématopoïétiques : quels progrès ?

Bronchiolitis obliterans (BO) is a severe complication of hematopoietic stem cell transplantation (HSCT). It is considered as a respiratory manifestation of chronic graft-versus-host disease. It is quite similar to the bronchiolitis obliterans after lung transplantation. Classical therapy associates steroids and immunosuppressive drugs, however theses procedure showed a modest efficacy and have an important morbidity. Recent progresses in the physiopathology of BO post-HSCT allow to use new treatments: mTOR inhibitors, immunotherapy, extra-corporeal photochemotherapy, and bronchial anti-inflammatory effects of azithromycin, statins or antileucotriens. This review will focus on the use of these new therapies in BO post-HSCT.

[Are investigations for underlying causes needed for the management of an adult patient with bronchiectasis?]. / La recherche d'une étiologie est-elle nécessaire à la prise en charge d'un adulte ayant une dilatation des bronches ?

Bronchiectasis may result from various causes. Recognition of these underlying causes may lead to specific management. Focal bronchiectasis are related to luminal blockage or extrinsic narrowing. The causative factors of diffuse bronchiectasis may be suggested by the predominant distribution of the disease and associated extrapulmonary manifestations. Primary immunodeficiencies cystic fibrosis, allergic bronchopulmonary aspergillosis, chronic Mycobacterium avium complex infection, and systemic diseases have to be looked for, even in patients with knowledge of a childhood respiratory infection.

[Pulmonary cystic adenomatoid malformation in an adult patient: an underdiagnosed disease]. / Malformation kystique adénomatoïde pulmonaire de l'adulte : une pathologie méconnue.

Currently, most congenital lower respiratory tract malformations are detected during pregnancy or at birth, thanks to antenatal imaging. However, a pulmonary congenital cystic adenomatoid disease may be found in adulthood. The diagnosis is difficult, due to its rarity. We present the case of a patient whose diagnosis of pulmonary cystic adenomatoid malformation was confirmed when she had tuberculosis. A lobectomy was performed, which enabled identification of tuberculosis and also multiple cysts of adenomatoid malformation. The risk posed by this malformation, i.e. the risk of developing bronchioloalveolar carcinoma and of infection or pneumothorax, is the incentive for proposing formal surgical removal.

[Management of the pulmonary complications of haematological malignancy]. / Approche diagnostique d'une pneumopathie chez un malade atteint d'hémopathie maligne.

The high frequency of pulmonary complications of haematological malignancy and the increasing number of patients treated for these disorders make it important that the respiratory physician has a structured diagnostic approach according to: 1 the immune deficiency due to the malignancy and/or the treatment administered; 2 the factors that can modify the risk of infection (anti infection prophylaxis and/or pre-emptive treatment); 3 co-morbidities; 4 extra-pulmonary manifestations. Two main situations can be identified: The patient is aplasic: Initially the pneumonias are predominantly of bacterial origin but may be fungal if the neutropenia is prolonged. The respiratory physician is faced with two problems: 1 the diagnosis of pneumonia; this may be helped by CT scanning; 2 The choice of antibiotics; this will depend on previous investigations. The patient is not aplasic: The lung disease may have many causes, mainly infectious but also drug related, tumoral, haemorrhagic or embolic. The main problem is the correct choice of investigations to establish an aetiological diagnosis. The collection of data according to a pre-established protocol based on simple factors (study of the notes and clinical examination) is one of the key elements for improving the prognosis of these patients whose management should be multidisciplinary following a pre-defined plan.

Pulmonary manifestations of multicentric Castleman's disease in HIV infection: a clinical, biological and radiological study.

The aim of the present study was to report clinical, radiological and bronchoalveolar lavage (BAL) findings in patients with pulmonary manifestations of HIV-associated multicentric Castleman's disease (MCD). This was a retrospective study of 12 patients with histologically proven MCD. Clinical manifestations were as follows: dyspnoea (nine out of 12 cases), cough (n = 10), bilateral crackles (n = 10), together with high fever, malaise, peripheral lymphadenopathy (n = 12), and hepatosplenomegaly (n = 10). Two patients developed acute respiratory distress syndrome. Chest radiographs and computed tomography scans showed reticular (n = 7) and/or nodular (n = 7) interstitial patterns, with mediastinal lymphadenopathy (n = 9), and bilateral pleural effusion (n = 3). Fibreoptic endoscopy was normal in all cases. BAL analysis showed hypercellularity (n = 6) and/or lymphocytosis (n = 6), and human herpesvirus-8 DNA was detected in two out of two cases. Specific stains and cultures for pathogens were negative. All patients received etoposide and/or vinblastine, and improved after 2-4 days. Relapses were frequent (50 attacks in 12 patients). Six patients developed a non-Hodgkin's lymphoma, and five died. In conclusion, the pulmonary manifestation of HIV-related multicentric Castleman's disease is an acute reticulo-nodular interstitial pneumonitis, associated with severe systemic symptoms and peripheral lymphadenopathy. In bronchoalveolar lavage fluid, cellularity is not specific and human herpesvirus-8 DNA is detected. The clinical course is specific due to a rapid onset and regression, frequent relapses and a high occurrence of non-Hodgkin's lymphoma.

[A rare cause of chronic respiratory insufficiency: arthrogryposis in adults]. / Une cause rare d'insuffisance respiratoire chronique: l'adulte.

Arthrogryposis is a congenital disease leading to multiple joint ankylosis in utero observed as sequellae at birth. Deformation of the chest produces respiratory failure usually seen at birth. We report a case in an adult which required intermittent nocturnal positive pressure nasal ventilation.