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Quantitative Computed Tomography in COPD: Possibilities and Limitations

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation. Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment.

Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process. Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions.

This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD.

Plasma N-terminal Pro-brain Natriuretic Peptide: A Prognostic Marker in Patients with Chronic Obstructive Pulmonary Disease

Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with secondary pulmonary hypertension and chronic lung disease with right ventricular overload. The aim of the present study was to investigate the use of plasma NT-proBNP levels as a prognostic marker of severe COPD with chronic respiratory failure and latent pulmonary hypertension.

Methods :Plasma NT-proBNP levels were measured in 61 patients with stable COPD. Plasma NT-proBNP levels, pulmonary function, PaO2, and PaCO2 levels and systolic pulmonary artery pressure were compared according to COPD severity. In addition, we examined correlations between plasma NT-proBNP levels and pulmonary function, PaO2, PaCO2, and systolic pulmonary artery pressure.

Results :The levels of plasma NT-proBNP significantly increased in patients with stage IV and stage III COPD compared to individuals with stage II COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The area under the receiver-operating characteristic curve of plasma NT-proBNP for severe to very severe COPD (FEV1 < 50%) was 0.707 (95% confidence interval [CI] 0.566–0.847, P = 0.008). Plasma NT-proBNP levels significantly correlated with %FEV1 (r = −0.557; P < 0.001), arterial blood gas parameters such as PaCO2 (r = 0.476; P < 0.001) and PaO2 (r = −0.347; P = 0.031), and systolic pulmonary artery pressure (r = 0.435; P = 0.001).

Conclusions : Plasma NT-proBNP levels increased significantly with disease severity, progression of chronic respiratory failure, and secondary pulmonary hypertension in patients with stable COPD. These results suggest that plasma NT-proBNP can be a useful prognostic marker to monitor COPD progression and identify cases of secondary pulmonary hypertension in patients with stable COPD.

Antiangiogenic Agents as Second-line Therapy for Advanced Non-Small Cell Lung Cancer.

With the approval of the antiangiogenic antibody bevacizumab in non-small cell lung cancer (NSCLC) and other malignancies, the tumor vasculature has emerged as a worthwhile therapeutic target.

Second-line therapies have the potential to improve overall survival and quality of life over best supportive care alone. Accordingly, phase II and phase III studies are actively evaluating antiangiogenic treatments in the second-line setting in NSCLC, and results are awaited. Such therapies include antiangiogenic antibodies, small molecule inhibitors, and vascular-disrupting agents.

This review will present the current landscape of angiogenesis inhibition in NSCLC, focusing on use as second-line therapy.

Tumor Vasculature as a Therapeutic Target in Non-small Cell Lung Cancer.

INTRODUCTION: To describe the molecular mechanisms relevant to angiogenesis inhibition and to critically evaluate the current evidence for the use of angiogenic inhibitors (AIs) in the treatment of non-small cell lung cancer (NSCLC).

METHODS: The literature on the basic concepts of tumor angiogenesis is reviewed. Published articles and major lung cancer conference abstracts were screened for reports on the use of AI in NSCLC patients and the National Institutes of Health clinical trials database was searched for relevant ongoing studies.

RESULTS: We delineate in this review the molecular and cellular aspects of angiogenesis and vasculogenesis and outline the relevance of these to lung cancer. Clinical studies of AIs in NSCLC reported to date as well ongoing studies are summarized. Major issues discussed include the choice of the right molecular target; characteristics of various tyrosine kinase inhibitors; potential drawbacks and concerns regarding the application of AIs in clinical practice, and major unanswered questions and future directions.

CONCLUSIONS: AIs have antitumor activity in NSCLC and have become part of the standard of care for patients with advanced nonsquamous cell carcinoma. Unfortunately, the gains have been modest and robust predictive biomarkers are urgently needed. Clinical trials to date have validated the tumor vasculature as a legitimate target, and as our understanding of the biology of tumor angiogenesis increases, exciting new therapeutic approaches are being explored.

Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology.

Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging.

We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL(-1) (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL(-1).

No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs.

Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in lung cancer patients

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