Prospective screening for ALK: clinical features and outcome according to ALK status.

The aim of this study was to analyse the clinico-pathological characteristics and outcomes of a cohort of French patients who were prospectively screened for Anaplastic Lymphoma Kinase (ALK) rearrangement. One hundred and sixteen consecutive patients screened for ALK rearrangement to be recruited into a crizotinib registration trial were included from eight French centres. ALK rearrangement was detected by fluorescence in situ hybridization. Seventeen patients (14.6%) were positive for ALK. ALK+ patients were younger (p = 0.049) and more likely to be males (p=0.032), non- or light-smokers (p = 0.048) and without underlying respiratory disease (p=0.025) compared to ALK- patients. Thyroid-transcription factor-1 expression was present in all ALK+ tumours. ALK+ tumours tended to have lymph node and brain metastases. In multivariate analyses, gender, smoking history and N stage were independently associated with ALK status. Median overall survival (OS) was not reached for ALK+ patients and was significantly longer than for ALK- patients (hazard ratio for death for ALK- patients 2.98; 95% CI [1.29-6.90], p=0.01). French ALK+ patients present a specific phenotype. ALK rearrangement should be determined to improve OS with an effective targeted therapy.

ANCA-associated lung fibrosis: analysis of 17 patients.

In this retrospective study, we analyzed 17 patients presenting with pulmonary fibrosis and a positive ANCA testing. This group was compared with a control group of 12 patients with IPF and negative ANCA testing. Patients were 15 males and 2 females, with a mean age of 66 years. Eight patients were past smokers, 3 current smokers and 6 non-smokers. Lung function tests at diagnosis were as follows (% predicted): total lung capacity 73%+/-18, vital capacity 82%+/-23, forced expiratory volume in 1 s (FEV(1)) 88%+/-24, carbon monoxide diffusion capacity of the lung 49%+/-2 (% predicted). Bronchoalveolar lavage results showed an increased cellularity with increased neutrophils counts. High resolution computed tomography of the chest showed prominent fibrosis with some degree of ground-glass attenuation in all patients. These characteristics were similar to the control group. Microscopic polyangiitis (MPA) was a major complicating event in ANCA-positive patients, occurring in 7 patients (anti-myeloperoxidase specificity in 5 patients). Pulmonary fibrosis predated occurrence of MPA in 6 patients and was diagnosed concomitantly with MPA in 1 patient. During the follow-up, 10/17 patients died. The death was directly related to vasculitis in 3 patients. We conclude that patients with pulmonary fibrosis should be evaluated for the presence of ANCA. Patients with positive ANCA testing, particularly if anti-myeloperoxidase, should be carefully monitored to detect the occurrence of microscopic polyangiitis.

Sarcoidosis in HIV-infected patients in the era of highly active antiretroviral therapy.

To analyze the impact of highly active antiretroviral therapy (HAART) on the characteristics and outcome of sarcoidosis in patients infected with human immunodeficiency virus (HIV), we identified HIV-infected patients in whom sarcoidosis was diagnosed between 1996 and 2000 from the admission registers of the pneumology departments of 12 hospitals in the Paris region (France). Sarcoidosis was diagnosed in 11 HIV-infected patients, of whom 8 were receiving HAART. HIV infection was diagnosed before sarcoidosis in 9 cases. At diagnosis of sarcoidosis, the mean CD4 cell count (+/-SD) was 390+/-213 cells/mm(3), and the mean plasma virus load was 4002+/-10,183 copies/mL. Sarcoidosis occurred several months after HAART introduction, when the CD4 cell count had increased and the plasma HIV load had decreased. Clinical and radiological characteristics, laboratory values for bronchoalveolar lavage fluid samples, and outcome after a long follow-up were similar for the patients receiving HAART and for HIV-uninfected patients.