Advantages of multidetector-row CT with multiplanar reformation in guiding percutaneous lung biopsies.

PURPOSE: This study aimed to assess the usefulness of multiplanar reformations (MPR) during multidetector-row computed tomography (MDCT)-guided percutaneous needle biopsy of lung lesions difficult to access with the guidance of the native axial images alone owing to overlying bony structures, large vessels or pleural fissures. MATERIALS AND METHODS: MDCT-guided transthoracic needle biopsy (TNB) was performed on 84 patients (55 men and 29 women; mean age 65 years) with suspected lung neoplasm by using a spiral MDCT scanner with the simultaneous acquisition of six slices per rotation. We determined the site of entry of the 22-gauge Chiba needle on native axial images and coronal or sagittal MPR images. We took care to ensure the shortest needle path without overlying large vessels, main bronchi, pleural fissures or bony structures; access to the lung parenchyma as perpendicular as possible to the pleural plane; and sampling of highly attenuating areas of noncalcified tissue within the lesion. RESULTS: Diagnostic samples were obtained in 96% of cases. In 73 patients, lesions appeared as a solid noncalcified nodule <2 cm; 11 lesions were mass-like. In 22, the biopsy required MPR guidance owing to overlying ribs (18), fissures (2) or hilar-mediastinal location (2). CONCLUSIONS: MDCT MPR images allowed sampling of pulmonary lesions until now considered unreachable with axial MDCT guidance because of overlying bony structures (ribs, sternum and scapulae) or critical location (hilar-mediastinal, proximity to the heart or large vessels). Compared with the conventional procedure, the use of MPR images does not increase the rate of pneumothorax or the procedure time.

Cisplatin versus carboplatin in combination with mitomycin and vinblastine in advanced non small cell lung cancer. A multicenter, randomized phase III trial.

BACKGROUND: In advanced not selected NSCLC chemotherapy achieved an advantage of approximately 1-2 months on median survival versus best supportive care. Chemotherapy seems to improve symptoms control, even if randomised studies with quality of life as first endpoint are lacking and often chemotherapy toxicity compromises the frail cost/benefit ratio. The aim of the present study is to evaluate the impact on QoL, substituting cisplatin, a pivot drug in NSCLC therapy, with carboplatin, an analogue with an improved toxicity profile. The combination of cisplatin with Mitomycin and Vinblastine was one of the most frequently used in the palliative setting at the time of design of our study. METHODS: Patients were randomized to receive MVP regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Cisplatin 100 mg/m2 d1) or MVC regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Carboplatin 300 mg/m2 d1) every 3 weeks. The QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13 questionnaires before chemotherapy, after one cycle, after three cycles, and then every 6 weeks in the first 6 months and every 3 months thenafter. RESULTS: From September 1994 to July 1997, 153 consecutive patients were randomized to MVP (75 patients) or MVC arm (78 patients). Despite difficulties in carrying out and analysing QoL items in such patients, the global QoL evaluated by the Spitzer's questionnaire suggested an advantage for MVC regimen (P=0.05) and a significant difference was observed in global health subdomain (P=0.04). The disease-related symptoms improved with time, and the benefits lasted for the entire treatment period. When evaluated with the EORTC questionnaire there was significantly less nausea and vomiting (P=0.0001), appetite loss (P=0.01), insomnia (P=0.03), constipation (P=0.01) and peripheral neuropathy (P=0.01) in favour of MVC, and a trend for less hair loss (P=0.05). The advantage lasted for all the duration of chemotherapy. No differences were observed in global quality of life subdomain (P=0.40) between the two regimen. QoL was the first endpoint and the statistical power was inadequate to assess other parameters. However, we reported a response rate of 43.1 and 38.6%, respectively, in MVP and MVC arm (P=0.59) and a median survival of 10.2 and 7.2 months, respectively, for cisplatin and carboplatin arm (P=0.39). CONCLUSIONS: The carboplatin containing regimen (MVC) has a significant better toxicity profile than the cisplatin containing (MVP) regimen as proven both by the EORTC questionnaires and by the WHO toxicity data reported by physicians. No significant differences in terms of response rate, time to progression and overall survival were observed between the two regimen. The two chemotherapy regimen showed a similar effectiveness in symptom palliation when evaluated with C30 addendum of EORTC QOL questionnaire. With the Spitzer's questionnaires a trend towards an improved quality of life index was observed during treatment with the carboplatin combination in comparison to the cisplatin combination. This difference, however, was not observed when the global quality of life was evaluated with the EORTC patients compiled questionnaires. A carboplatin containing regimen with better toxicity profile and a similar potentiality for symptoms control offers an option in comparison to similar cisplatin containing combinations in the palliative treatment of advanced NSCLC.

Increased exhaled nitric oxide in patients with stable chronic obstructive pulmonary disease.

BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. Since chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation, a study was undertaken to determine NO levels in the exhaled air of patients with COPD. METHODS: Two groups of patients with clinically stable COPD were studied, 10 current smokers and 10 ex-smokers. Two control groups of healthy subjects consisting of 10 current smokers and 20 non-smokers were also studied. Exhaled NO levels were measured by the collection bag technique and NO chemiluminescence analyser. RESULTS: Mean (SE) levels of exhaled NO in ex-smokers and current smokers with COPD (25.7 (3.0) ppb and 10.2 (1.4) ppb, respectively) were significantly higher than in non-smoker and current smoker control subjects (9.4 (0.8) ppb and 4.6 (0.4) ppb, respectively). In current smokers with COPD exhaled levels of NO were significantly lower than in ex-smokers. In this latter group of patients there was a significant negative correlation between smoking history (pack years) and levels of exhaled NO (r = -0.8, p = 0.002). A positive correlation was seen between forced expiratory volume in one second (FEV1) and levels of exhaled NO (r = 0.65, p = 0.001) in patients with COPD. CONCLUSIONS: These data show that exhaled NO is increased in patients with stable COPD, both current and ex-smokers, compared with healthy control subjects.

Predominant TH1 cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease.

BACKGROUND: Previous studies have provided evidence for an inflammatory process in the large airways of subjects with chronic obstructive pulmonary disease (COPD), consisting predominantly of activated T cells. No data are available on the TH1 /TH2 T-cell cytokine pattern in this disease. OBJECTIVE: We sought to characterize the TH1 /TH2 T-cell cytokine pattern in subjects with COPD. METHODS: We examined the IFN-gamma and IL-4 expression in peripheral blood CD4+ and CD8+ T cells from 20 patients with COPD and 25 control subjects by using a flow cytometric method of intracellular cytokine detection. We also examined the expression of 2 surface activation markers (CD25 and HLA-DR) on peripheral blood CD4+ and CD8+ T cells. RESULTS: There was an increased percentage of IFN-gamma-producing cells (30.3% [range, 12.9% to 60.4%] vs 19.1% [range, 4% to 31.2%], P =.003) and a decreased percentage of IL-4-producing cells (4.55% [range, 0.6% to 11.3%] vs 9.5% [2.1% to 21.3%], P =.0008) among peripheral blood CD4+ T cells from the patients with COPD compared with control subjects. There was no significant difference between the 2 groups in the percentage of peripheral blood CD8+ T cells producing IFN-gamma or IL-4 or in the percentage of peripheral blood CD4+ and CD8+ T cells expressing CD25 and HLA-DR. CONCLUSION: These findings provide evidence for a TH1 -like immune response of peripheral blood CD4+ T cells in subjects with COPD.

Neutrophils infiltrating bronchial epithelium in chronic obstructive pulmonary disease.

In order to characterize neutrophil and eosinophil presence in the airways of patients with chronic obstructive pulmonary disease (COPD), bronchoscopy with bronchial washings and bronchial biopsies was performed in 12 smoking stable COPD subjects and 18 normal non-smoking control subjects. Bronchial biopsies were examined by light microscopy using plastic embedding and histochemical techniques to identify different cell types. Bronchial washing fluid of COPD patients was characterized by a predominance of neutrophils (P = 0.001), and a slight, but significant (P = 0.03), increase of eosinophil fraction. Subjects with COPD had higher number of neutrophils in the epithelium (P = 0.01), and eosinophils in the lamina propria (P = 0.01) than did control subjects. The thickness of reticular basement membrane was increased for COPD patients in comparison to control subjects (P = 0.01). The present study provides evidence of neutrophil infiltration both in bronchial washing and bronchial epithelium of patients with COPD, suggesting that the source of neutrophils in airway lumen may be the bronchial mucosa. Although less common than in asthma, airways of COPD subjects reveal eosinophil presence and airway remodelling.

Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease.

Cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD). Although the precise sequence of events that leads a smoker to experience airway obstruction is not completely clear, airway inflammation is a relevant factor. To investigate airway inflammation, 12 nonatopic smoking COPD patients with a forced expiratory volume in one second (FEV1) < or = 75% predicted and 10 normal nonsmoking subjects (NS) were studied with bronchoscopy and bronchial lavage (BL). Serum immunoglobulin (Ig)E levels of COPD patients correlated with the smoking history (r=0.7, p=0.008). In BL of COPD patients there was an increase of neutrophils (median, range) (COPD 62.6x10(3), 1.2-323, NS 1.35, 0-19.2, p=0.001), eosinophils (COPD 1.6, 0-6.9, NS 0.15, 0-3.7, p=0.035), the levels of interleukin (IL)-8 (COPD 1079 pg x mL(-1), 121-2,500, NS 20.4, 7.2-59, p=0.001), myeloperoxidase (MPO) (COPD 752 microg x L(-1), 11-5,500, NS 22.1, 8-70, p=0.001) and eosinophil cationic protein (ECP) (COPD 21.5 microg x L(-1), 1.8-161, NS 2, 1.8-4.9, p=0.001). Significant correlations were found in BL of COPD patients between IL-8 and neutrophils (p=0.02), MPO and neutrophils (p=0.02), IL-8 and MPO (p=0.0001) and ECP and eosinophils (p=0.02). In addition, the ratios between the BL levels of MPO and the number of neutrophils and between ECP levels and eosinophils were higher in COPD patients than in NS (p=0.03 and 0.01, respectively). These data suggest that cigarette smoke is associated with increased amounts of airway interleukin-8, a chemotactic factor for neutrophils and eosinophils. Recruited neutrophils and eosinophils are activated and they release increased amounts of inflammatory mediators capable of damaging the bronchial tissue.

Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task Force (FONICAP).

In the present multicentre randomized phase II trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and cisplatin 80 mg m(-2) on day 1 every 28 days), PIN (cisplatin 80 mg m(-2) day 1, ifosfamide 3 g m(-2) day 1 and vinorelbine 25 mg m(-2) day 1 and 8 every 21 days) and CaN (carboplatin 350 mg m(-2) day 1 and vinorelbine 25 mg m(-2) days 1 and 8 every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49 patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent of the patients had stage IV disease. Response rates, calculated on an 'intention to treat' basis, were as follows: MVP, 14.3% (95% CI 5.94-27.2%); PIN, 16.7% (95% CI 7.4-30.2%); and CaN, 14% (95% CI 5.3-27.9%). The overall median survivals were 256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively. Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN respectively. This multicentre phase II randomized trial shows that MVP, PIN and CaN can be administered on an outpatient basis with acceptable toxicities. Unfortunately, the three regimens showed an activity significantly lower than that reported in previous single-institution phase II trials.

Hypophosphatemia in course of chronic obstructive pulmonary disease. Prevalence, mechanisms, and relationships with skeletal muscle phosphorus content.

Serum phosphorus levels (Ps), dietary intake of phosphorus, and renal phosphate handling indexes were evaluated in 158 patients with chronic obstructive pulmonary disease (COPD) of varying degrees of severity; moreover, skeletal muscle phosphorus content (Pm) was measured in muscle samples obtained by quadriceps femoris needle biopsy in 14 of the same patients. Hypophosphatemia (Ps less than or equal to 2.5 mg/dl) was found in 34 (21.5 percent) of 158 patients without differences between groups of COPD patients presenting increasing severity of respiratory illness. No relationship was found between serum levels and dietary intake of phosphorus; hypophosphatemia was associated with low renal phosphate threshold (TmPO4/GFR) values in 31 (91 percent) of 34 patients. The prevalence of hypophosphatemia was significantly higher among COPD patients taking one or more drugs commonly used in COPD and known as negatively influencing renal phosphate handling: xanthine derivatives, corticosteroids, loop diuretics, and beta 2-adrenergic bronchodilators. Short-term administration of therapeutic doses of these drugs in COPD patients previously not taking any drug reduced TmPO4/GFR values; phosphaturic effect of short-term theophylline administration on renal phosphate handling was additive to that of long-term assumption of the drug. Muscle phosphorus content was both reduced in COPD patients as compared with control subjects and significantly correlated to serum phosphorus levels and to TmPO4/GFR values. The present investigation revealed a high prevalence of hypophosphatemia among COPD patients as well as a defect in renal phosphate reabsorption secondary, at least in part, to pharmacologic therapy. Moreover, it also suggests that in COPD patients muscle phosphorus content is likely to be reduced in presence of hypophosphatemia.

Hypercapnic-hypoxemic chronic obstructive pulmonary disease (COPD): influence of severity of COPD on nutritional status.

In 90 patients with hypercapnic-hypoxemic chronic obstructive pulmonary disease (COPD), noninvasive anthropometric and biochemical nutritional indices were measured to assess the prevalence and features of malnutrition in COPD and to analyze the relationship between nutritional depletion and the severity of the disease. A significant inverse relationship was found between PaCO2 and body weight; a parallel decrease of both somatic proteins and body-energy stores of fat appears to be paired with decreasing body weight. Deterioration of nutritional status occurred in the COPD patients considered despite seemingly adequate calorie and protein intakes, although in patients with more severe impairment of pulmonary gas exchange, calorie intake was significantly lower compared with basal energy expenditure. In the course of hypercapnic-hypoxemic COPD malnutrition is common, it is related to the severity of the disease as judged by the need for hospitalization and degree of impairment of gas exchange, and it may be present despite apparently adequate nutrient intake.