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Background: Forced expiratory flow-volume curves are commonly used to assess the degree of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). In mechanically ventilated subjects, expiratory airways obstruction can only be estimated from relaxed expirations. The aim of this study was to quantify the degree of airways obstruction from relaxed expiratory flow-volume curves in mechanically ventilated patients with COPD.Methods: As measure of airflow obstruction, the effective time constant during the last 50% of expired volume (tau) was calculated. For bedside monitoring, tau was recalculated as the slope of the flow during the last 50% of expired volume (SF50). In order to study reproducibility, the variables were calculated from consecutive breaths and at different levels of end-expiratory lung volume (EEV). The SF50 and the tau-were correlated with the forced expiratory volume in 1 s (FEV1) measured prior to the start of ventilatory support.Results: Twenty-seven patients were studied with a FEV1 expressed as percentage predicted of 31 +/- 12% (mean +/- SD). The SF50 amounted to 19 +/- 10 degrees. A positive linear correlation was established between SF50 and the FEV1, (%pred), (r = 0.90, P < 0.0001). The tau showed an exponential relationship with FEV1 (%pred), (r2 = 0.78). From 5 consecutive breaths the mean variation coefficient of SF50 was 5 +/- 2%. Changes of delta EEV from 0.05 to 1.00 L did not affect the SF50-values. In 12 patients, mechanically ventilated for respiratory diseases other than COPD, mean tau and SF50 were significantly different from the COPD-patients (P < 0.0001).Conclusions: This study indicates that relaxed expiratory flow-volume curves can be used to assess airflow obstruction in mechanically ventilated patients with COPD. This information can be used to adapt ventilatory settings. [ABSTRACT FROM AUTHOR]

Background Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) administered concurrently with chemotherapy did not improve outcome in non-small-cell lung cancer (NSCLC). However, in preclinical models and early phase noncomparative studies, pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect. Patients and methods A randomized phase II study was carried out in patients with advanced NSCLC who had progressed on or following first-line chemotherapy. Erlotinib 150 mg daily (monotherapy) or erlotinib 150 mg during 15 days intercalated with four 21-day cycles docetaxel for squamous (SQ) or pemetrexed for nonsquamous (NSQ) patients was administered (combination therapy). After completion of chemotherapy, erlotinib was continued daily. Primary end point was progression-free survival (PFS). Results Two hundred and thirty-one patients were randomized, 115 in the monotherapy arm and 116 in the combination arm. The adjusted hazard ratio for PFS was 0.76 [95% confidence interval (CI) 0.58–1.02; P = 0.06], for overall survival (OS) 0.67 (95% CI 0.49–0.91; P = 0.01) favoring the combination arm. This improvement was primarily observed in NSQ subgroup. Common Toxicity Criteria grade 3+ toxic effect occurred in 20% versus 56%, rash in 7% versus 15% and febrile neutropenia in 0% versus 6% in monotherapy and combination therapy, respectively. Conclusions PFS was not significantly different between the arms. OS was significantly improved in the combination arm, an effect restricted to NSQ histology. Study Registration number NCT00835471. [ABSTRACT FROM PUBLISHER]

Purpose: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m2 on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3–4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of day 1 without a decrease in response rate (RR). Methods: Patients received gemcitabine 1,250 mg/m2 on days 1 and 8, carboplatin AUC 5 on day 1 (arm A) or day 8 (arm B). Drugs were administered over a 21-day cycle. Toxicity and RR were evaluated weekly and every second cycle, respectively. Results: 71 patients were enrolled into the study. We found 79% (95% CI 61–91%) grade 3–4 toxicity (neutropenia and thrombocytopenia) in arm A and 50% (95% CI 32–68%) in arm B; 66% grade 3–4 thrombocytopenia in arm A and 26% in arm B. We observed 30% grade 4 hematological toxicity in arm A and 3% in arm B. In arm A an overall RR of 20% (95% CI 7.7–38.6%) was seen, and 18.2% (95% CI 7–35.5%) in arm B. Conclusions: Although the study was prematurely closed, the current data are of interest. The schedule with carboplatin on day 8 is associated with substantially lower grade 3–4 neutropenia and thrombocytopenia with comparable dose intensity and RR. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: In mechanically ventilated patients, the expiratory time constant provides information about the respiratory mechanics and the actual time needed for complete expiration. As an easy method to determine the time constant, the ratio of exhaled tidal volume to peak expiratory flow has been proposed. This assumes a single compartment model for the whole expiration. Since the latter has to be questioned in patients with chronic obstructive pulmonary disease (COPD), we compared time constants calculated from various parts of expiration and related these to time constants assessed with the interrupter method.Design: Prospective study.Setting: A medical intensive care unit in a university hospital.Patients: Thirty-eight patients (18 severe COPD, eight mild COPD, 12 other pathologies) were studied during mechanical ventilation under sedation and paralysis.Measurements and Results: Time constants determined from flow-volume curves at 100%, the last 75, 50, and 25% of expired tidal volume, were compared to time constants obtained from interrupter measurements. Furthermore, the time constants were related to the actual time needed for complete expiration and to the patient's pulmonary condition. The time constant determined from the last 75% of the expiratory flow-volume curve (RCfv75) was in closest agreement with the time constant obtained from the interrupter measurement, gave an accurate estimation of the actual time needed for complete expiration, and was discriminative for the severity of COPD.Conclusions: In mechanically ventilated patients with and without COPD, a time constant can well be calculated from the expiratory flow-volume curve for the last 75% of tidal volume, gives a good estimation of respiratory mechanics, and is easy to obtain at the bedside. [ABSTRACT FROM AUTHOR]

Background: There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers.Methods: A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants.Results: Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9.Conclusions: In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.). [ABSTRACT FROM AUTHOR]

Background: Translating results from randomized clinical trials (RCTs) to individual patients in clinical practice is challenging, as treatment effects can vary substantially among individuals. Data from RCTs can be used for individualized treatment effect prediction, to identify patients who benefit from specific treatments. In this study, we developed and validated a prediction model for estimating absolute treatment effect of pemetrexed plus carboplatin versus single-agent pemetrexed in the second-line treatment of non-squamous non-small-cell lung cancer (NSCLC). Patients and methods: Using data of relapsed patients with advanced non-squamous NSCLC from the NVALT-7 trial, a Weibull model for prediction of gain in median progression-free survival (PFS) by pemetrexed-carboplatin was derived based on patient and tumor characteristics. The model was externally validated in the GOIRC 02-2006 trial. The applicability of the model for guiding clinical decision-making was evaluated using decision curve analysis. Results: A wide distribution of predicted gain in median PFS by pemetrexed-carboplatin over pemetrexed was found, with a median of 0.7 months (interquartile range: -0.1 to 1.5 months). Patients who benefited most included women, those with stage IV, high body mass index and/or adenocarcinoma. External validation showed satisfactory calibration and moderate discrimination (C-index: 0.61, 95% confidence interval 0.56-0.67). Decision curve analysis confirmed that the model adequately identified patients who benefit from pemetrexed-carboplatin, as prediction-based treatment led to improvement in net benefit with regard to PFS and overall survival when assuming a treatment threshold of 0-5 months gain in PFS, compared with other treatment strategies. Conclusions: The effects of pemetrexed-carboplatin can be predicted for individual patients based on routinely available patient and tumor characteristics. There is important heterogeneity in the effects on PFS of pemetrexed-carboplatin versus pemetrexed in pretreated patients with advanced non-squamous NSCLC. Individualized prediction of treatment effect could be used to guide shared decision-making by discriminating patients who benefit most, to improve clinical outcome. [ABSTRACT FROM AUTHOR]