Abstract: PURPOSE: To test toxicity, tolerability, time to progression, survival and response rate in the 3-day administration of topotecan (T) followed by carboplatin (C), and then etoposide (E) in a study for small cell lung cancer (SCLC) treatment. PATIENTS: 44 chemotherapy-naive patients with SCLC (median age 63.5, PS 0-1). ED was present in 28 patients. METHODS: Each treatment cycle consisted of T (0.8mg/m(2) on days 1-3), C (AUC=5, day 3) and a standard oral dose of E (100mg on days 15-17). Cycles were repeated every 32 days and up to eight were performed. Responders received radiotherapy to the primary site (50Gy) after the 4th cycle and complete responders also received PCI. RESULTS: Complete response (CR) was achieved in 4 patients, partial response (PR) in 18, stable disease in 10 and PD in 12. Median survival was 280 (+/-36.7) days and median time to progression 137 days. 11 patients developed grade 3/4 neutropenia and 3 patients grade 3/4 anaemia. Non-haematological toxicity was mild. CONCLUSION: In contrast to ORR, PFS and survival were quite similar to those of SCLC patients suffering from ED treated by a platinum-etoposide regimen. The T/C/E combination was well tolerated and with low toxicity, but without improvement in the ORR and survival in comparison to platinum analogue regimes.

Abstract: Background: Eosinophilic lung diseases comprise a group of heterogeneous pulmonary disorders linked by increased eosinophils in bronchoalveolar lavage fluid (BALF). There is supporting evidence that natural killer (NK) cells participate in the regulation of eosinophilic inflammation. Objective: Our aim was to investigate the relationship between eosinophils and NK cells in BALF in patients with different interstitial lung diseases (ILDs) focusing on eosinophilic pneumonias. Methods: Of 114 patients who presented with increased BALF eosinophils (>5%), 74 patients were classified into the following groups: 27 had eosinophilic pneumonia (EP), 17 had idiopathic pulmonary fibrosis (IPF), 16 had hypersensitivity pneumonitis (HSP) and 14 had cryptogenic organizing pneumonia (COP/BOOP). Total BALF cells, cell density and cell differential counts were assessed and lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3-CD16/56+ (NK) and CD3+CD16/56+ (NKT) were determined by flow cytometry. Results: Significant differences were observed in the percentages of lymphocytes (p < 0.001) and CD3+CD16/56+ cells (p = 0.023) among patient groups. In patients with EP, the percentage of eosinophils correlated positively with the number of CD3-CD16/56+ cells (r = 0.522, p = 0.005), the percentage of CD3-CD16/56+ cells (r = 0.690, p < 0.001), and the absolute count of CD3+CD16/56+ absolute cells (r = 0.609, p = 0.001). However, in patients with IPF, HSP or COP/BOOP, no correlation between the percentage of eosinophils and CD3-CD16/56+ or CD3+CD16/56+ cells was observed. Conclusions: Eosinophil inflammation seems to develop through a different pathway in EP compared to other ILDs.

Abstract: ABSTRACT: INTRODUCTION: Hydrocarbon pneumonitis is an acute, intense pneumonitis resulting from aspiration of volatile hydrocarbon compounds with low viscosity and surface tension, most of which are members of the paraffin, naphthene and aromatic classes. CASE PRESENTATION: Six hours after participating in a party for teenagers, a 16-year-old boy developed dyspnea, cough, a fever (39 degrees C) and chest pain. A chest radiograph showed infiltration in the right middle lobe. The patient reported alcohol abuse during the party and an episode of vomiting a few hours thereafter. He also reported practicing a fire-eating performance at the party using liquid paraffin, but was unaware of inhaling any of it. The radiographic infiltration was diagnosed as an aspiration pneumonia and he was treated at the local health center with antibiotics. Five days later, because of clinical deterioration, he was referred to a pulmonary clinic. A chest computed tomography scan was performed which showed consolidation with an air bronchogram in the right middle lobe and areas of atelectasis and ground glass opacities in the middle and lower right lobes. Spirometry revealed severe restriction of lung function. A bronchoscopy revealed inflamed, hyperemic mucosa. Bronchoalveolar lavage fluid revealed lipid-laden alveolar macrophages, which were detected by lipid staining, and neutrophilia. The patient was finally diagnosed with hydrocarbon pneumonitis and he was treated with systemic steroids and antibiotics. After 6 days of treatment there was complete clinical and significant radiologic regression. CONCLUSION: Hydrocarbon pneumonitis should be included in the differential diagnosis of pneumonias. Recent exposure to volatile hydrocarbons provides a basis for clinical diagnosis, as symptoms and radiologic findings are not specific.

Abstract: OBJECTIVE: To evaluate the time course of coagulation markers in the early postburn period and clarify the role of coagulation alterations in organ failure and in mortality prognosis. DESIGN AND SETTING: This prospective study was conducted in the burn ICU of a tertiary hospital. PATIENTS: 45 patients with severe thermal burn injury. MEASUREMENTS AND RESULTS: Clinical data and coagulation and fibrinolysis parameters were measured during the first postburn week. The ICU 28-day mortality rate was 33%. Significant differences in the time course of coagulation markers were observed between survivors and nonsurvivors. SOFA score distinguished between patients with overt and nonovert disseminated intravascular coagulation (DIC) during the overall investigation period. Presence of overt DIC was related to mortality (OR=0.1). Antithrombin, protein S, plasminogen activator inhibitor 1, and SOFA score on day 3, protein C on day 5, and thrombin/antithrombin complexes on day 7 revealed a good prognostic value for ICU mortality, according to the area under ROC curves. CONCLUSIONS: Severe thermal injury is associated with the early activation of coagulation cascade, presence of DIC, organ failure, and increased mortality.

Abstract: It was hypothesised that, apart from right ventricular (RV) dysfunction, patients with idiopathic pulmonary fibrosis (IPF) also exhibit left ventricular (LV) impairment, which may affect disease progression and prognosis. The aim of the present study was to evaluate LV performance in a cohort of IPF patients using conventional and tissue Doppler ECG. IPF patients exhibiting mild-to-moderate pulmonary arterial hypertension (mean age 65+/-9 yrs; n = 22) and healthy individuals (mean age 61+/-6 yrs; n = 22) were studied. Conventional and tissue Doppler ECG were used for the evaluation of RV and LV systolic and diastolic function. In addition to the expected impairment in RV function, all patients showed a characteristic reversal of LV diastolic filling to late diastole compared with controls (early diastolic peak filling velocity (E)/late diastolic peak filling velocity 0.7+/-0.2 versus 1.5+/-0.1, respectively). Patients with IPF also exhibited lower peak myocardial velocities in early diastole (E(m); 5.7+/-1.1 versus 10.3+/-1.6 cm x s(-1), respectively), higher in late diastole (A(m); 8.9+/-1.3 versus 5.5+/-0.8 cm x s(-1), respectively), lower E(m)/A(m) ratio (0.6+/-0.1 versus 1.9+/-0.5, respectively) and higher E/E(m) ratio (10.8+/-3 versus 6+/-0.6, respectively), all indicative of LV diastolic dysfunction. Moreover, LV propagation velocity was significantly lower in IPF patients (46+/-13 versus 83+/-21 cm x s(-1), respectively). Physicians should be aware that patients with idiopathic pulmonary fibrosis exhibit early impairment of left ventricular diastolic function.

Abstract: Severe burn injury is characterized by the activation of coagulation, decreased fibrinolytic activity and decreased natural anticoagulant activity. The aim of our study was to investigate the effect of antithrombin (AT) administration on coagulation status and on organ function in the early post-burn period. Thirty-one patients were admitted to the burn intensive care unit and were then randomised into two groups (AT-treated and non-AT-treated) for four consecutive days after thermal injury. The clinical data, coagulation and fibrinolysis parameters were compared and the adverse effects were monitored. Significant differences in the time course of coagulation markers (thrombin/AT complexes, tissue plasminogen activator, D-dimer) were observed between AT-treated and non-AT treated groups. According to the International Society on Thrombosis and Haemostasis criteria, disseminated intravascular coagulation (DIC) diagnosis was made in 28 of 31 patients. The presence of overt DIC was associated with mortality (p < 0.001). The Sequential Organ Failure Assessment (SOFA) score time trend differed significantly between the two investigation groups (decreased in the treated group and did not change in the non-AT-treated group). AT-treated patients had an absolute reduction in a 28-day mortality of 25% as compared to the non-AT-treated group (p = 0.004). No treatment related side effects were observed. Treatment with AT seems to affect the coagulation status and reduce multiple organ failure incidence and mortality in the early post-burn period.

Abstract: OBJECTIVES: The aim of pleurodesis in malignant pleural effusions is to prevent reaccumulation of the fluid, symptoms, and avoid the need for repeated hospitalization for thoracentesis. The purpose of this study was to evaluate the efficacy and safety of erythromycin as a pleural sclerosing agent. METHODS: Over a 2-year period, 34 patients with a symptomatic, recurrent, malignant pleural effusion who referred for chest tube drainage and pleurodesis were included. They had not received prior intrapleural therapy and had predicted survival of at least 1 month. All underwent pleural drainage and chemical pleurodesis with erythromycin. Complications and response to pleurodesis, according to clinical and radiographic criteria after 90 days, were recorded. RESULTS: The overall response was 88.2%. Complete response (no reaccumulation of pleural fluid after 90 days) was observed in 27 patients (79.4%). Partial response (reaccumulation of fluid but without symptoms, not requiring drainage) was observed in 3 (8.8%). No response (symptomatic reaccumulation of fluid that required drainage) was observed in 4 (11.8%). All patients experienced pleurodynia that was treated with administration of paracetamol and/or dextropropoxyphene. Sinus tachycardia and concurrent mild systemic hypertension were observed 2 and 4 hours after pleurodesis. Both of them were attributed to pleurodynia as there was remission with analgesics. CONCLUSIONS: This study suggests that erythromycin is effective and safe as a sclerosing agent for pleurodesis in patients with recurrent malignant pleural effusions.

Abstract: BACKGROUND: There are limited reports in the literature concerning right ventricular (RV) performance in patients with non end-stage idiopathic pulmonary fibrosis (IPF) who exhibit mild to moderate pulmonary hypertension (PH). We evaluated RV functional impairment in such a cohort using both conventional echocardiography and tissue Doppler imaging (TDI) and in addition we assessed the association of specific TDI indices with survival. METHODS: Twenty-two clinically stable patients with non-end stage IPF and mild to moderate PH were assessed. Twenty-two healthy individuals served as controls. We evaluated RV systolic and diastolic function and further estimated peak pulmonary artery systolic pressure (PASP). In addition, by combining TDI and Doppler echocardiography, we calculated the ratio of trans-tricuspid E-wave velocity to early diastolic tricuspid annulus velocity (RV E/Em). Patients were followed for a median period of 22 months and the incidence of death was recorded. RESULTS: Both echocardiographic modalities revealed impaired RV systolic and diastolic function in the IPF group compared to controls. A significant negative correlation was observed between RV E/Em and PASP (r = -0.5, p = 0.018). The probability of survival was 54.5% for those patients with RV E/Em < 4.7 versus 100% for those with an index > 4.7 (log-rank statistic 5.81, p = 0.016). CONCLUSIONS: TDI modality may serve as an alternative to conventional ultrasound technique for risk stratification and PH estimation in non end-stage IPF patients.

Abstract: BACKGROUND: Expiratory flow limitation (EFL) is one of the main mechanisms contributing to dyspnea in patients with chronic obstructive pulmonary disease but has not been explored in patients with pleural effusion. OBJECTIVES: It was the aim of this study to determine whether patients with pleural effusion exhibit EFL and to investigate the effect of therapeutic thoracentesis on EFL. PATIENTS AND METHODS: The study was performed on 21 patients with pleural effusion who were subjected to thoracentesis and measurement of pleural pressure (PP). Spirometry and estimation of flow limitation by the negative expiratory pressure technique were performed before and after thoracentesis. RESULTS: Statistically significant differences were observed in all spirometric parameters. No correlation between the increase in lung volumes and flows and any of the aspirated fluid parameters was observed. Before thoracentesis, 14 out of 21 patients were flow limited, compared with 7 patients after thoracentesis (chi(2) = 6.151, p = 0.013). Mean values of flow limitation before and after thoracentesis differed significantly. The decrease in flow limitation did not correlate with the increase in the spirometric parameters, the aspirated fluid volume or PP decrease. CONCLUSIONS: In the majority of patients with pleural effusion, flow limitation improves after thoracentesis. Flow limitation may be a contributing factor to the sensation of dyspnea in these patients.

Abstract: OBJECTIVE: To estimate the diagnostic value of serum PCT, CRP, leukocyte count and temperature as markers of sepsis in critically ill ICU burn patients. DESIGN AND SETTING: Prospective, observational study in a four bed Burn Intensive Care Unit. PATIENTS: Forty-three patients admitted in a Burn ICU were included in our study. MEASUREMENTS AND RESULTS: Serum PCT, CRP concentrations, WCC (white cell count), neutrophils and temperature were measured within the first 24h after-burn and daily thereafter. Severity of organ failure was estimated by sequential organ failure assessment (SOFA) score. Every day we classified all patients in one of the following three categories: non-systemic inflammatory condition (non-SIRS), SIRS non-infected and SIRS 2 infected or sepsis. Patients with infected SIRS differ significantly from non-infected SIRS in PCT (11.8+/-15.8 versus 0.63+/-0.0.43, respectively, p < 0.001). On the other hand, WCC, temperature and neutrophils did not differ significantly between patients with SIRS non-infected and infected SIRS. CRP was elevated in all three groups but didn't differ significantly between SIRS non-infected and septic patients. Area under receiver operating curves was 0.975 and showed reasonable discriminative power (p = 0.002, 95% CI, 0.91-1.035) in predicting of sepsis only for PCT. CONCLUSIONS: Serum procalcitonin levels can be used as an early indicator of septic complication in patients with severe burn injury.

Abstract: BACKGROUND: Idiopathic pulmonary fibrosis is the most common idiopathic interstitial pneumonia. The human herpesviruses and especially Epstein-Barr virus have been implicated in the etiology of idiopathic pulmonary fibrosis in a number of studies. AIM: The aim of this study was to investigate the potential association between idiopathic pulmonary fibrosis and Epstein-Barr virus. METHODS: Bronchoalveolar lavage fluid and sera were collected from 63 patients out of whom 17 suffered of idiopathic pulmonary fibrosis and 46 of other interstitial lung diseases. Sera from 50 healthy, age-matched individuals were also collected. Antibodies to the early, nuclear, and capsid antigens of Epstein-Barr virus were determined by enzyme immunoassay and indirect immunofluorescence. Additionally polymerase chain reaction was performed in bronchoalveolar lavage fluid in order to investigate the presence of Epstein-Barr virus DNA. Positive polymerase chain reaction results were confirmed by nucleotide sequencing. RESULTS: Statistically significant differences were observed in the frequency of IgA antibodies to viral capsid antigen among patients with idiopathic pulmonary fibrosis, patients with other interstitial lung diseases and healthy controls (60%, 24.4% and 22% respectively, p = 0.013). Epstein-Barr virus DNA was detected in the bronchoalveolar lavage fluid of 3 patients with idiopathic pulmonary fibrosis but in none of the patients with other diseases (p = 0.024). CONCLUSIONS: The results of this study support the association between IPF and EBV, at least in some cases, and provide evidence that BALF is an alternative for the detection of viral DNA in patients with IPF. However further investigation is required concerning the etiology of idiopathic pulmonary fibrosis.

Abstract: BACKGROUND: The type and mode of presentation of pulmonary sarcoidosis (radiologic stage, activity) influence alveolar lymphocyte number and subsets as well as other inflammatory cells. AIM: To investigate the variations in alveolar cells, lymphocyte subsets and NK-cells in different radiological stages of active pulmonary sarcoidosis. METHODS: 85 untreated, newly diagnosed patients (32 male, 53 female), median age 47.2+/-14.7 years were investigated. Patients were classified into chest x-ray stages (33 stage I, 27 stage II, 14 stage III and 11 stage IV disease). Bronchoalveolar lavage was performed with 4 portions of 50 mL. Total cells and cell differentials were counted, while CD3+, CD4+, CD8+, CD19+, CD3-CD16/56+ (NK-cells) and CD3+CD16/56+ (NKT-cells) were determined by flow cytometry. Results: Lymphocytosis was high in all stages. Significant differences were found in: a) CD4 between stages I and II and I and IV. b) CD8 between stages I and IV and c) NK and NKT cells between stages I and III. CONCLUSIONS: Variations were observed in alveolar cells and lymphocyte subsets in different stages of pulmonary sarcoidosis. Cells exhibiting cytotoxic activity were increased with stage progression, CD8 from stage I to IV, NK and NKT cells from stage I to III. These cells may be involved in the inflammatory process regulating granuloma formation.

Abstract: BACKGROUND: Oxidant/antioxidant imbalance has been reported in various respiratory diseases including pneumonia. However, the role of blood antioxidants has not been fully discussed. OBJECTIVES: The aim of this exploratory study was to assess serum total antioxidant status (TAS) in patients with community-acquired pneumonia (CAP) and the probable correlation with the severity of the disease. METHODS: Thirty patients (22 men, 8 women; mean age of 48 +/- 21 years) and 10 healthy nonsmokers (mean age 44 +/- 16 years) were studied. Clinical, laboratory and radiological findings were recorded on the day of admission and on the 7th day. A severity score was calculated using the Fine scale. Serum TAS was measured at the same time points using a colorimetric method. RESULTS: On admission, TAS (TAS1) was significantly lower than on the 7th day (TAS2) (0.84 +/- 0.13 mmo/l vs. 1.00 +/- 0.17 mmo/l; p = 0.0001) and compared with the healthy subjects (0.84 +/- 0.13 vs. 1.19 +/- 0.09 mmol/l; p < 0.001). TAS change (TAS2 - TAS1) was statistically significantly more marked in smokers (0.17 vs. 0.28, p = 0.001), in patients with factors predisposing to CAP (0.12 vs. 0.37; p = 0.000) and in patients with gram-negative pneumonia (0.16 vs. 0.35; p = 0.000). On the other hand, change in TAS was statistically significantly less marked in patients with lobar pneumonia (0.27 vs. 0.17; p = 0.001). Additionally, TAS change was positively correlated to white blood count on admission (r = 0.39; p = 0.029). CONCLUSIONS: It is concluded that serum TAS is decreased in patients with CAP, suggesting the presence of oxidative stress, and that change in TAS seems to be influenced by disease severity. TAS measurement may be useful in estimating the severity of CAP and is a probable indication for the administration of antioxidants in the management of the disease.

Abstract: Oxidative processes, mediated by oxygen free radicals are recognized to contribute significantly to the inflammatory pathology of bronchial asthma. An imbalance between oxidants and antioxidants has also been proposed in this disease. This study examines the serum total antioxidant status (TAS) in asthmatic patients with severe exacerbation of their disease and the probable correlation with clinical or laboratory findings. The TAS was measured in 20 patients (10 men and 10 women, with a mean age of 41.95 +/- 20.75 years), using a colorimetric method. On the days of admission and discharge, the forced expiratory volume in 1 sec (FEV1), the partial arterial oxygen pressure (PaO2), and severity criteria were recorded and correlated with TAS at the same time. The TAS was also measured in 10 healthy subjects (8 men and 2 women, mean age of 39 +/- 9 years). A statistically significant decrease of TAS was observed on admission day compared to that on discharge day (0.98 +/- 0.08 vs. 1.12 +/- 0.17 mmol/L, p < 0.001, respectively, paired t-test) suggesting the presence of oxidative stress during an asthma attack. The TAS on admission was also statistically significantly decreased compared to that of normal subjects (0.98 +/- 0.08 vs. 1.19 +/- 0.09 mmo/L, p < 0.001, respectively, paired t-test). A statistically significant correlation was observed between FEV1 change and TAS change, from admission to discharge day (r = 0.58, p = 0.007, Pearson correlation). Finally, a statistically significant correlation was found between FEV1 change and TAS on discharge day (r = 0.65, p = 0.002). Decreased TAS was found during an asthma attack, probably as a consequence of increased oxidative stress. The TAS change was correlated with severity criteria, such as FEV1. Therefore, it seems that measurement of TAS could be a simple and useful tool in the evaluation of an asthma attack. The supplementary administration of antioxidants in future needs further clarification.

Abstract: We investigated the efficacy of docetaxel (D) in combination with carboplatin (C) in the treatment of non-small cell lung cancer (NSCLC) patients. Since 1996, 123 with inoperable NSCLC were enrolled in the study; 120 (108 males, 12 females; mean age 58.0+/-8.3 years) were evaluated. Of those, 46 patients had squamous carcinoma, 44 adenocarcinoma, 11 large cell carcinoma and 19 undifferentiated tumours. Eligibility criteria included, documented inoperable NSCLC, WHO performance status (PS) 0-1, age up to 70 years, and normal renal and hepatic function. A total of 622 cycles of chemotherapy (CHT) (median 7 (95% CI 6.2-7.47), courses per patient) were administered. Each cycle consisted of 100 mg/m(2) of docetaxel in a 2-h infusion with C at a dose of area under the curve (AUC) of 6 on day 1. This regimen was repeated every 28 days up to eight cycles. Of the patients, five (4%) achieved complete response, 49 (40%) partial response, 47 (39%) had stable disease and 19 (15%) had progressive disease. The median survival was 12 months for all patients, 12 for the four patients with stage IIb disease, 18 for the patients with stage IIIa disease, 20 for the 29 patients with stage IIIb disease, and 11 for the 65 stage IV patients. The median time to progression was 8 months (90 patients). Toxicity was, grade 3/4 neutropenia, 18 patients (15%); grade 3/4 anaemia, 6 patients (5%); and tolerable peripheral neuropathy, 16 patients (13.3%). Responders received radiotherapy (total dose, 50 Gy in 4 weeks) between the 6th and 8th cycle. Among responders with initial stage IIIb disease, 7 (5%) underwent surgical resection. Patients with early progression of the disease received the same dose of radiotherapy between 2nd and 3rd cycle. The study is ongoing, and six patients (5%) are still alive (after 3 years). Preliminary results indicate that the D/C combination is very active in the treatment of NSCLC with tolerable toxicity. It appears that this drug combination is also good as neoadjuvant therapy in inoperable NSCLC patients.

Abstract: BACKGROUND: It has been suggested that the Hering-Breuer reflex (HBR) is unimportant in adults during normal tidal breathing and that it is elicited only if tidal volume is increased above a certain critical threshold. OBJECTIVE: The aim of this study was (1) to study the occurrence of the HBR in adults with normal pulmonary function and (2) to examine if changes in lung mechanics have any effect on the HBR. METHODS: We examined 11 adults with normal pulmonary function, 8 patients with chronic destructive pulmonary disease (COPD) and 3 with interstitial fibrosis (IF). All subjects were lightly sedated with fentanyl, intubated and ventilated with a Servo-900 ventilator. Inspiratory and expiratory flow (and after integration, volume) and mouth pressure were recorded from the endotracheal tube with a pneumotachograph and a pressure transducer. Pressure support ventilation was applied in all patients and functional residual capacity (FRC) was measured with the N(2) washout method. Mean (Te(mean)) and maximal expiratory time (Te(max)) were determined for each individual for 20 breaths. Following several breaths to establish a stable baseline the airway was occluded at end inspiration by a shutter. A positive HBR was interpreted as longer Te(occ) than Te(max) (Te(occ)/Te(max), %). Occlusion was maintained until negative airway pressure occurred and the occlusion time (Te(occ)) was measured. We attempted occlusions after the addition of 5 cm H2O positive end-expiratory pressure (PEEP) and subsequently with 10, 15 and 20 cm H(2)O PEEP. Te(occ) was measured of progressively larger lung volumes. To examine the HBR sensitivity in the three groups, we plotted the lung volumes of occlusion against the corresponding Te(occ)/Te(max). RESULTS: The ratio Te(occ)/Te(max) increased from 167.5 +/- 82.5 at normal FRC to 474 +/- 200.2 s (PEEP(20)). On the contrary, in patients with COPD, Te(occ)/Te(max) increased from 125.2 +/- 34 to 193.7 +/- 74.2 (p < 0.05). CONCLUSIONS: The HBR was positive in all subjects. COPD patients were found to be less sensitive to volume changes when compared with normal controls and with IF patients.