Louis-Jean Couderc

Pneumocystis jirovecii pneumonia.

Pneumocystis jirovecii has gained attention during the last decade in the context of the AIDS epidemic and the increasing use of cytotoxic and immunosuppressive therapies. This article summarizes current knowledge on biology, pathophysiology, epidemiology, diagnosis, prevention, and treatment of pulmonary P jirovecii infection, with a particular focus on the evolving pathophysiology and epidemiology. Pneumocystis pneumonia still remains a severe opportunistic infection, associated with a high mortality rate.

A Proof-of-Concept, Randomized, Controlled Trial of Omalizumab in Patients With Severe, Difficult-to-Control, Nonatopic Asthma

BACKGROUND While up to 50% of patients with severe asthma have no evidence of allergy, IgE has been linked to asthma, irrespective of atopic status. Omalizumab, an anti-IgE monoclonal antibody, is reported to significantly benefit a subset of patients with severe, persistent, allergic asthma. Therefore, we investigated whether omalizumab has biologic and clinical effects in patients with refractory nonatopic asthma. METHODS Forty-one adult patients who, despite daily treatment with or without maintenance oral corticosteroids, had severe, nonatopic, refractory asthma according to GINA (Global Initiative for Asthma) step 4, were randomized to receive omalizumab or placebo in a 1:1 ratio. The primary end point was the change in expression of high-affinity IgE receptor (FcεRI) on blood basophils and plasmacytoid dendritic cells (pDC2) after 16 weeks. The impact of omalizumab on lung function and clinical variables was also examined. RESULTS Compared with placebo, omalizumab resulted in a statistically significant reduction in FcεRI expression on basophils and pDC2 (P < .001). The omalizumab group also showed an overall increase in FEV1 compared with baseline (+250 mL, P = .032; +9.9%, P = .029). A trend toward improvement in global evaluation of treatment effectiveness and asthma exacerbation rate was also observed. CONCLUSIONS Omalizumab negatively regulates FcεRI expression in patients with severe nonatopic asthma, as it does in severe atopic asthma. Omalizumab may have a therapeutic role in severe nonatopic asthma. Nonetheless, our preliminary findings support further investigation to better assess the clinical efficacy of omalizumab. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01007149; URL: www.clinicaltrials.gov and European Clinical Trials Database, EudraCT; No.: 2009-010937-38; URL: https://www.clinicaltrialsregister.eu.

Interstitial lung disease and anti-Jo-1 antibodies: difference between acute and gradual onset

Aim: A multicentre retrospective study was undertaken to examine patients with interstitial lung disease (ILD) with the initial clinical manifestation of an anti-synthetase syndrome (anti-Jo-1 antibodies), and to analyse the characteristics and long-term outcome of these patients according to their clinical presentation (acute or gradual onset), treatment and adverse events related to treatment. Methods: 32 patients, 15 (47%) presenting with acute onset and associated respiratory insufficiency (group A) and 17 (53%) with gradual onset (group G) were examined. Myositis was diagnosed at admission in only 31% of cases and was observed during follow-up in 56% of cases, but the prevalence did not differ between the two groups. Results: Fever and radiological patterns including diffuse patchy ground-glass opacities, basal irregular lines and consolidation on high-resolution CT scan were more frequent in group A than in group G. More patients in group G had neutrophils in the bronchoalveolar lavage fluid and autoantibodies other than anti-Jo-1 (rheumatoid factor, anti SSa/SSb) than in group A. The percentage of patients in whom the ILD improved at 3 months was significantly higher in group A than in group G (13/15 vs 9/17; p = 0.006). In contrast, after 12 months, most patients with ILD progression were in group A and were treated with corticosteroids alone. A combination of corticosteroids and an immunosuppressive drug was required in most cases (84%) at the end of the follow-up period. Severe adverse effects of treatment were observed and varicella zoster virus infection was frequent. Conclusions: Early testing for anti-synthetase antibodies, particularly anti-Jo-1, and creatine kinase determination are useful procedures in patients presenting with ILD. Treatment with corticosteroids and immunosuppressive drugs is required in most patients. At the end of the study, around two-thirds of patients had stable ILD while the other third had disease progression with respiratory insufficiency.

Lung cancer in patients with HIV infection and review of the literature

Background. The improved survival of patients since the use of highly active antiretroviral treatments has lead to the reporting of non-AIDS defining tumors, such as lung cancer.Methods. Analysis of the records of 22 HIV-infected patients with lung cancer (LC) diagnosed in three hospitals located in the Paris area (France).Results. Twenty-one patients were smokers. The patients (86% male, 14% female) had a median age of 45 yr (range, 33–64 yr). Risk factors for HIV infection were intravenous drug use in 5 patients, homosexual transmission in 10 patients, and heterosexual transmission in 7 patients. At diagnosis of LC, seven patients had previously developed a CDC-defined AIDS manifestation, the median CD4 cell count was 364/mm3 (range 20–854/mm3) and median HIV1 RNA viral load was 3000 copies/mL. The most frequent histological subtype was squamous cell carcinoma (11 cases). A stage III–IV disease was observed in 75% of the patients. Only one patient had a small-cell lung carcinoma. Twenty-one patients received combined specific therapy, of which six patients underwent surgery for the LC. The median overall survival was 7 mo. No opportunistic infections occurred during LC therapy.Conclusions. LC occurs at a young age in HIV-infected smokers. LC is not associated with severe immunodeficiency. The prognosis is poor because of their initial extensive disease and a poor response to therapy. However, surgery appears to improve outcome in much the same way as in the general population.

Clinical characteristics and prognostic factors of pulmonary MALT lymphoma

Mucosa-associated lymphoid tissue-derived (MALT) lymphoma, a low grade B-cell extranodal lymphoma, is the most frequent subset of primary pulmonary lymphoma. Our objective was to evaluate the initial extent of disease and to analyse the characteristics and long-term outcome of these patients. All chest and pathological departments of teaching hospitals in Paris were contacted in order to identify patients with a histological diagnosis of primary pulmonary lymphoma of the MALT subtype. 63 cases were identified. The median age was 60 yrs. 36% of cases had no symptoms at diagnosis. 46% of patients had at least one extrapulmonary location of lymphoma. The estimated 5- and 10-yr overall survival rates were 90% and 72%, respectively. Only two of the nine observed deaths were related to lymphoma. Age and performance status were the only two adverse prognostic factors for survival. Extrapulmonary location of lymphoma was not a prognostic factor for overall survival or for progression-free survival. Treatment with cyclophosphamide or anthracyclin was associated with shorter progression-free survival, when compared with chlorambucil. The survival data confirm the indolent nature of pulmonary MALT lymphoma. Better progression-free survival was observed with chlorambucil when compared with cyclophosphamide or anthracyclin.

The spectrum of malignancies in HIV-infected patients in 2006 in France: The ONCOVIH study†‡

Since no large descriptive studies of incident cancers in HIV‐infected patients are available in France, the nationwide cross‐sectional ONCOVIH study aimed to prospectively report new malignancies diagnosed in HIV‐infected patients in cancer centers and HIV/AIDS centers. We estimated the number of cancers in France for the year 2006 using the capture–recapture methods with two sources: ONCOVIH and the FHDH ANRS‐CO4 cohort, as well as the completeness of the sources. Incidence and relative risks (RR) to the general population were estimated. In 2006, 672 new malignancies in 668 patients were reported in ONCOVIH; the most common were non Hodgkins lymphoma (NHL, 21.5%), Kaposis sarcoma (KS, 16.0%), lung cancer (9.4%), anal cancer (8.2%), Hodgkins lymphoma (7.6%), skin cancers excluding melanoma (6.8%), and liver cancer (5.6%). Based on the capture‐recapture approach, the estimated number of malignancies was 1320 and non‐AIDS‐defining malignancies (NADM) represented 68% of cases. The overall ascertainment of malignancies were 53%, and 59%, in the ONCOVIH study, and the FHDH ANRS‐CO4 cohort, respectively. The estimated incidence of cancer among HIV‐infected patients was 14 per 1000 person‐years. Compared with the general population, the estimated RR in HIV–infected patients was 3.5 (95%CI 3.3–3.8) in men and 3.6 (95%CI 3.2–4.0) in women, and was particularly elevated in younger patients. Even in the era of combined antiretroviral therapy, the incidence of cancer is higher in HIV‐infected persons than in the general population. A large variety of malignancies were diagnosed, and the majority were NADM.

Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease.

BACKGROUND Pulmonary hypertension (PH) complicating systemic sclerosis (SSc)-related interstitial lung disease (ILD) is usually associated with a poor prognosis. However, data are either lacking or scarce on prognostic factors in this condition. The objectives of this study were to compare the survival of patients with ILD-associated PH (PH-ILD) or pulmonary arterial hypertension (PAH) and to determine whether the severity of PH has prognostic value in SSc-associated PH-ILD. METHODS Consecutive patients with SSc and PH-ILD (n = 47) or PAH (n = 50) confirmed by right-sided heart catheterization were included in a cross-sectional analysis. PH was classified as mild (mean pulmonary arterial pressure [mPAP] ≤ 35 mm Hg) or moderate to severe (mPAP > 35 mm Hg). RESULTS As compared with patients with PAH, subjects with PH-ILD were younger, were more frequently men with a history of smoking, had more frequently diffuse SSc, less frequently anticentromere antibodies, and a lower FVC/diffusing capacity of lung for carbon monoxide (DLCO) ratio. They had a worse prognosis than patients with PAH (3-year survival of 47% vs 71%, respectively; P = .07). Patients with mild PH-ILD had similar poor outcomes when compared with those with moderate to severe PH-ILD. Pericardial effusion (hazard ratio [HR], 2.44; P = .04) and lower DLCO (HR, 0.96; P = .01) were the only independent factors predictive of a poor survival in the PH-ILD group. CONCLUSIONS Patients with SSc with PH-ILD had a different phenotype and a worse prognosis than those with SSc and PAH. Lower DLCO and presence of pericardial effusion were predictive of a poor outcome in PH-ILD, whereas mPAP seemed to have no prognostic significance.

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 Castlemans 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-Hodgkins lymphoma, and five died. In conclusion, the pulmonary manifestation of HIV-related multicentric Castlemans 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-Hodgkins lymphoma.

Prognostic significance of serum p53 antibodies in patients with limited‐stage small cell lung cancer

p53 tumour suppressor gene alterations are one of the most frequent genetic events in lung cancer. A subset of patients with p53 mutation and cancer exhibited circulating serum anti‐p53 self‐antibodies (p53‐Ab). The prevalence of these antibodies in lung cancer is currently being analysed in a multicentric study. In a group of homogeneous SCLC patients, p53‐Ab were detected in 20/97 (20.6%) individuals. In this group of patients, Coxs multivariate analysis identified disease extent (p = 0.022), WHO initial performance status greater than 0 (p = 0.005), and the absence of a complete response after 6 months of treatment (p < 0.0001) as independent prognostic variables, with p53‐Ab being of borderline significance (p = 0.051). In the subset of limited‐stage SCLC patients, Coxs multivariate analysis found p53‐Ab (p = 0.033), WHO initial performance status greater than 0 (p = 0.028), and absence of a complete response (p < 0.001) to be independent prognostic variables. Thus, actuarial analysis showed that patients with limited‐stage SCLC and p53‐Ab had a median survival time of 10 months, whereas limited‐stage SCLC patients without p53‐Ab had a 17‐month median survival time (p = 0.014).Therefore, serum assay of p53‐Ab could help to identify a population of SCLC patients with an especially poor prognosis. This population could represent patients with tumours harboring aggressive p53 mutations. Int. J. Cancer (Pred. Oncol.) 89:81–86, 2000.

Pulmonary manifestations in adult patients with chronic granulomatous disease

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by failure of superoxide production in phagocytic cells. The disease is characterised by recurrent infections and inflammatory events, frequently affecting the lungs. Improvement of life expectancy now allows most patients to reach adulthood. We aimed to describe the pattern of pulmonary manifestations occurring during adulthood in CGD patients. This was a retrospective study of the French national cohort of adult patients (≥16 years old) with CGD. Medical data were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds of adult patients. Their incidence was significantly higher than in childhood (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per year per patient) and asymptomatic in 37% of the cases. They often required lung biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned 28% of adult patients, frequently associated with a concomitant fungal infection (40%). They were more frequent in patients with the X-linked form of CGD. Immune-modulator therapies were required in most cases (70%). Respiratory manifestations are major complications of CGD in adulthood. Noninfectious pulmonary manifestations are as deleterious as infectious pneumonia. A specific respiratory monitoring is necessary. Pulmonary involvement is a major concern in adult CGD patients, making specific respiratory monitoring necessary http://ow.ly/FjaRS