Self-perceived quality of sleep among COPD patients in Greece: the SLEPICO study.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide accompanied by a substantial social and economic burden for the patient and the society. Poor sleep quality among COPD patients is frequently unnoticed and unaddressed by physicians and patients themselves, although it is a major source of further deterioration of these patients' quality of life. The aim of the present study was to record the quality of sleep in COPD patients among the Greek population and correlate these findings with various features of these patients, using the COPD and Asthma Sleep Impact Scale (CASIS). This was a cross-sectional observational study. Forty different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, CASIS questionnaire results, COPD assessment test, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, inhaled COPD treatment report) were collected from 3454 nation-wide COPD patients (Greece). The study sample consisted of COPD patients, mainly male (73%) with a median age of 69 years and a median BMI of 27.2. More than half of COPD patients (60.6%) suffered from moderate disease severity and 23.8% from severe disease, while less than half (42.1%) suffered from at least one exacerbation of the disease over the last year prior study enrollment. About 14% reported frequent to very frequent issues affecting their sleep quality, between a fourth and a third of them reported occasional night sleep disturbances, and at least half of them reported no or very infrequent problems in their night sleep. Our study indicates that the COPD assessment test (CAT) and the spirometry-based disease severity can predict the poorness in the quality of sleep (F2,3451 = 1397.5, p < 0.001, adj. R2 = 0.45) as assessed by CASIS score, and that the latter also correlates with age (ρ = 0.122, p < 0.001) and disease duration (ρ = 0.104, p < 0.001). On the contrary, there appears to be no correlation between sleep quality and number of exacerbations. Finally, untreated patients with COPD suffer from poorer quality of sleep compared to treated subjects, independently of the use of inhaled corticosteroids (F2,3451 = 21.65, p < 0.001). The results of the SLEPICO study show that increased age, prolonged disease duration, and especially CAT score ≥ 10, and severe COPD stage, might act as important indicators for deterioration in the quality of sleep, with potential consequences in the daily routine of those patients, thus urging potentially for further pharmacological interventions or modifications.

Pegylated Liposomal Doxorubicin HCL (Caelyx) in combination with Sandostatin LAR as salvage therapy in patients with small-cell lung cancer.

BACKGROUND: The aim of the present study was to evaluate the efficacy of Pegylated Liposomal Doxorubicin (Caelyx) combined with Sandostatin LAR as salvage treatment of small cell lung cancer (SCLC) in platinum-pretreated patients. PATIENTS AND METHODS: Nine pretreated patients (median age 53.5 years, PS: 0-1) with histologically confirmed SCLC were treated with Caelyx 40 mg/m2 (i.v.) on day 1 and Sandostatin LAR 30 mg (i.m.) on day 1 every 28 days. Four (44%) out of the nine patients had received two prior regimens and five (55%) were refractory to front-line chemotherapy. RESULTS: No complete or partial responses were observed. Disease stabilization was obtained in two (22%) patients. The median overall survival was 18.7 months and the median time to progression was 9.1 months. CONCLUSION: The combination of Caelyx and Sandostatin LAR was inactive as salvage treatment in this poor prognosis group of patients with relapsed SCLC. However, the combination would merit further investigation in patients pretreated with one prior regimen.

Phase II study of cisplatin-combined schedules as second-line chemotherapy in patients with non-small cell lung cancer.

BACKGROUND: The aim of this study was to evaluate the effectiveness of cisplatin- (CDDP) combined chemotherapy in non-cisplatin pretreated patients with non-small-cell lung cancer (NSCLC). The second cytotoxic drug administered was either etoposide or gemcitabine. First-line treatment was based on paclitaxel combined with either carboplatin or vinorelbine. PATIENTS AND METHODS: Seventy-eight patients with histologically- or cytologically- confirmed NSCLC, having failed front-line treatment, were enrolled. All patients received 80 mg/m2 of cisplatin as second-line treatment, on day 1, repeated every 3 weeks; in 48 patients the second agent was etoposide (120 mg/m2) on days 1, 2 and 3, repeated every 3 weeks and in 30 patients 1 g/m2 of gemcitabine on day 1, repeated every 3 weeks. RESULTS: All patients were evaluable for response and toxicity. No complete responses were observed. Thirteen (16.67%) patients achieved partial response, 42 (53.85%) stable disease and 23 (29.49%) had disease progression. The median duration of response was 4 months (range 2-8+ months), median time to tumor progression (TTP) 5 months (range 2-9 months) and median survival time after starting second-line chemotherapy, 6 months (range 2-9+ months). Toxicity was acceptable: 9 patients presented with nephrotoxicity (11.54%) and 13 (16.67%) with grade 3-4 neutropenia. CONCLUSION: The cisplatin combination as second-line treatment in patients with NSCLC exhibited a notable degree of activity and tumor growth control was evidenced by the 16.67% partial response and 53.85% disease stability.

Genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes and lung cancer risk.

Genetic polymorphisms of the genes encoding for the xenobiotic metabolizing enzymes result in individual variations in the efficiency of detoxification of environmental carcinogens, and have been extensively associated with variable risk for lung neoplasms in different ethnic and environmental backgrounds. In this study, using PCR-RFLP based assays, we investigated the distribution of genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 genes in Greek lung cancer patients (N=122) and healthy controls (N=178). The frequency of CYP1A1 m1 homozygous genotype was 0.04 in patients and 0.02 in controls (detected in 4.10% of patients and in 1.69% of controls, respectively), that of GSTM1 null genotype was 0.52 in patients and 0.54 in controls, whereas those of GSTT1 null genotype was 0.17 and 0.11, in patients and controls, respectively. The GSTM1 null genotype was more frequent in adenocarcinoma, as well as in lung cancer patients with history of chronic obstructive pulmonary disease (COPD). The GSTT1 null genotype correlated with advanced age of the patients at the time of diagnosis. Three combinations of rare genotypes - in subjects carrying simultaneously deviations from the common genotype in more than one gene - were over-represented in lung cancer patients, compared to control population, and were furthermore significantly associated with history of heavy tobacco consumption in lung cancer patients. The results imply involvement of specific genotype combinations of CYP1A1, GSTM1 and GSTT1 alleles in the development of lung cancer in heavy smokers.

Paclitaxel and vinorelbine combination in advanced inoperable adenocarcinoma of the lung: a phase II study.

BACKGROUND: The purpose of this study was to determine the efficacy of paclitaxel (PCT) combined with vinorelbine (VRL) in adenocarcinoma of the lung. PATIENTS AND METHODS: Untreated inoperable patients with metastatic disease were enrolled and underwent front-line treatment with a new combination as follows: a 30-minute infusion of VRL at a dose of 25 mg/m2 followed by a 3-hour infusion of PCT 135 mg/m2. Chemotherapy was repeated every 2 weeks with the intention of administering 9 cycles. RESULTS: Fifty-four out of 58 enrolled patients were assessable; the median age was 63 years (range 48-81). All patients were chemotherapy-naïve and all had histologically- or cytologically- confirmed adenocarcinoma. Twenty-seven patients (50%) responded: 5 with complete response (9.3%) and 22 with partial response (40.7%); 17 patients had stable disease (31.5%) and 10 showed disease progression (18.5%). Median response duration was 6 months (range 2-14.5) and median survival was 10 months (range 2-35+). The main adverse reaction was myelotoxicity in 87% of the patients, of whom only 8 (14.8%) had grade 4 neutropenia which in 4 cases (7.4%) was febrile. No patient required dose reduction, but treatment was postponed by one week in 4 patients a total of nine times. Patients received 98.6% of the planned dose. CONCLUSION: The PCT and VRL combination is an active first-line treatment for lung adenocarcinoma. These two cytotoxic drugs produce acceptable toxicity when repeated every 2 weeks.

Reduced intracellular Mg concentrations in patients with acute asthma.

STUDY OBJECTIVES: To determine the intracellular and extracellular Mg concentrations in patients with acute asthma and their correlation with parameters expressing the disease severity. PATIENTS: Thirty patients with acute asthma (FEV(1), 56% predicted [SD, 14.5]), 20 patients with stable asthma (FEV(1), 97% predicted [SD, 10]), and 20 healthy subjects (FEV(1), 97% predicted [SD, 8]). METHODS: Mg concentrations in erythrocytes and plasma were measured four times: at hospital admission, after 2 days, after 5 days, and at hospital discharge. Percentage of predicted FEV(1) and peak expiratory flow rate variability were recorded simultaneously. Similar measurements were carried in all study groups. RESULTS: Mg concentrations of healthy subjects and patients with stable asthma remained unchanged in both plasma and erythrocytes. Initial Mg content in erythrocytes was significantly lower in patients with acute asthma (1.77 fmmol per cell; 95% confidence interval [CI], 1.71 to 1.83) compared to normal subjects (1.94 fmmol per cell; 95% CI, 1.82 to 2.00) and patients with stable asthma (1.92 fmmol per cell; 95% CI, 1.87 to 1.96) [p < 0.0001], and it increased significantly after the resolution of the exacerbation (from 1.77 fmmol per cell [95% CI, 1.71 to 1.83] at hospital admission to 1.90 fmmol per cell [95% CI, 1.83 to 1.98] at hospital discharge; p < 0.0001). No correlation was observed between parameters of disease severity and the initial values of Mg concentrations in erythrocytes and plasma. CONCLUSIONS: Acute asthma is associated with lower erythrocyte Mg content while plasma levels remain unchanged. This decrease in intracellular Mg content occurs regardless of the severity of the exacerbation and returns to normal values after control has been achieved.