Non CF-bronchiectasis: Aetiologic approach, clinical, radiological, microbiological and functional profile in 277 patients.

BACKGROUND AND OBJECTIVES: Non-Cystic Fibrosis (CF) bronchiectasis is common in Greece but little attention has been paid to the investigation of its aetiology, clinical, radiological, microbiological and lung function profile. METHODS: We prospectively evaluated patients with non-CF bronchiectasis confirmed by high resolution computed tomography (HRCT) of the chest. Aetiology, clinical data, radiology score, microbiological profile and lung function were investigated. RESULTS: We evaluated 277 patients (170 women) with bronchiectasis (mean age: 60.5 ± 16 years), 64% of them being non-smokers. Post-infectious (25.2%) and past tuberculosis (TB) (22.3%) were the most commonly identified underlying conditions, while no cause was found in 34% of the patients. The main symptoms were cough (82%), mucopurulent sputum (80%), dyspnea (60%) and haemoptysis (37%). Mean duration of symptoms was 9.7 (SD 10.7) years. Infectious exacerbations were observed in 67.5% of the patients with a mean frequency of 2.3 (SD 1.4) per year. The most frequent lung function pattern was the obstructive (43.1%) while 38% of the patients had normal spirometry. Pseudomonas aeruginosa was the most common pathogen yielded in sputum cultures (43%) followed by Haemophilus influenzae (12.6%). Patients with P. aeruginosa had a more long-standing disease and worse lung function. Radiological severity of the disease was mainly related to impaired lung function, P. aeruginosa isolation in sputum and frequent exacerbations. CONCLUSION: Data indicate that in Greece, "past" tuberculosis remains an important cause of bronchiectasis. P. aeruginosa was the predominant pathogen in the airways, associated with disease severity, while the most common lung function impairment was obstruction.

Oxidative DNA damage and somatic mutations: a link to the molecular pathogenesis of chronic inflammatory airway diseases.

BACKGROUND: Acquired somatic mutations induced by oxidative stress may contribute to the molecular pathogenesis of chronic inflammatory airway diseases. The objective of this study was to assess the intensity of oxidative DNA damage and the presence of microsatellite DNA instability (MSI), a marker of acquired somatic mutations, in patients with COPD, patients with noncystic fibrosis bronchiectasis, and control subjects. METHODS: Induced sputum and peripheral blood from 97 subjects were analyzed; 36 patients with COPD, 36 patients with bronchiectasis, 15 smokers without COPD, and 10 healthy control subjects. DNA was extracted and analyzed for MSI. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a specific marker of oxidant-induced DNA damage, was measured in serum and sputum supernatants. RESULTS: None of the patients with bronchiectasis or control subjects (non-COPD smokers, healthy subjects) exhibited any genetic alteration. In contrast, MSI was found in 38% of COPD specimens. Sputum 8-OHdG was statistically significantly increased in COPD when compared with subjects with bronchiectasis (P = .0002), smokers without COPD (P = .0056), and healthy subjects (P = .0003). Sputum 8-OHdG in MSI-positive patients with COPD differed significantly from that of MSI-negative patients with COPD (P = .04) and smokers without COPD (P = .008), but was not statistically different (P = .07) among MSI-negative patients with COPD and smokers without COPD. Serum 8-OHdG was significantly increased in MSI-positive compared with MSI-negative patients with COPD (P = .001), but was not statistically significant in smokers without COPD (P = .09). Serum 8-OHdG was increased in smokers without COPD compared with MSI-negative patients with COPD (P = .009). CONCLUSIONS: There is a clear disparity in COPD regarding oxidant-induced DNA damage and somatic mutations. This may reflect a difference in the oxidative stress per se or a deficient antioxidant and/or repair capacity in the lungs of patients with COPD.

Comparison of cisplatin-paclitaxel combination versus cisplatin-etoposide in patients with small-cell lung cancer: a Phase III study.

Cisplatin-paclitaxel and cisplatin-etoposide combination therapies were compared in limited and extensive disease in patients with small-cell lung cancer. The primary objectives were to determine median and overall survival, time to tumor progression and tolerance and the secondary objective, the response rate. From January 2003 till July 2007, 108 patients were enrolled in the study. All patients had histologically- or cytologically-confirmed small-cell lung cancer. All patients were chemotherapy and radiotherapy naive. The patients were designated to receive six cycles: in the investigational Arm A, cisplatin, 80 mg/m(2) and paclitaxel 175 mg/m(2) were infused on day 1 (1 cycle) and repeated every 3 weeks. In the control Arm B, cisplatin, 80 mg/m(2) was administered on day 1 and etoposide, 120 mg/m(2) per day was given on days 1-3 (1 cycle), every 3 weeks. In Arm A, 6 (11.3%) patients achieved a complete response and 32 (58.1%), a partial response; in Arm B, 7 (12.7%) patients achieved a complete response and 32 (58.2%) a partial response. The median survival time in Arm A patients was 12 months and in Arm B, 13 months, p=0.354. The time to tumor progression (TTP) was 8 and 6 months for Arms A and B, respectively (p=0.060). Toxicity, although common in both Arms, was acceptable. Neutropenia, anemia and diarrhea were higher in the control Arm. The cisplatin-paclitaxel combination is not superior to cisplatin-etoposide with respect to survival, TTP, toxicity and response rate. The former combination could be applied as an alternative chemotherapy regimen for patients with limited or advanced small-cell lung cancer.