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Nintedanib: A Novel Therapeutic Approach for Idiopathic Pulmonary Fibrosis.

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Nintedanib: A Novel Therapeutic Approach for Idiopathic Pulmonary Fibrosis.

Respir Care. 2014 Apr 29;

Authors: Dimitroulis IA

Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with no clear etiology and few therapeutic options. Growth factors that act as mediators in the development of this disease might be important therapeutic targets. Nintedanib is a triple-tyrosine kinase inhibitor and a potent antagonist of growth factors such as platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor, and it is currently evaluated in clinical trials as a potential IPF therapy. Treatment with nintedanib may slow decline in lung function, decrease the frequency of exacerbations, and improve quality of life in subjects with IPF. This observation, together with extensive safety and pharmacokinetic data from studies of nintedanib in malignancy, led the way for the clinical development of this drug in IPF. Observations from clinical trials, together with the preclinical data, suggest that nintedanib may become an important therapeutic option for individuals with IPF. High-dose nintedanib improved the quality of life, slowed the progression of lung fibrosis and the decline of lung function, and reduced the rate of exacerbations in individuals with mild and moderate IPF. This is a short review based on the available data (September 2013) on nintedanib.

PMID: 24782550 [PubMed - as supplied by publisher]

Current Status of Oncothermia Therapy for Lung Cancer.

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Current Status of Oncothermia Therapy for Lung Cancer.

Korean J Thorac Cardiovasc Surg. 2014 Apr;47(2):77-93

Authors: Szasz A

Abstract
Lung cancer is one of the most common malignant tumors, and it has the highest death rate. Oncothermia is a feasible and successful treatment for lung cancer. Results show a remarkable survival benefit for patients, with a good quality of life. The treatment has no, or in some cases mild, side-effects and could decrease the adverse effects of the complementary treatment. Applying oncothermia together with other treatment methods could increase the effects and result in better performance. A comparison of studies demonstrates a good correspondence in the data, which strengthens the reliability of the studies, and clearly shows the feasibility of the application of oncothermia to treating all kinds of pulmonary malignancies including non-small-cell and small-cell primary tumors, and all of the metastatic diseases of the pulmonary system.

PMID: 24782955 [PubMed - as supplied by publisher]

Beyond the Genome: Epigenetic Mechanisms in Lung Remodeling.

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Beyond the Genome: Epigenetic Mechanisms in Lung Remodeling.

Physiology (Bethesda). 2014 May;29(3):177-185

Authors: Hagood JS

Abstract
The lung develops from a very simple outpouching of the foregut into a highly complex, finely structured organ with multiple specialized cell types that are required for its normal physiological function. During both the development of the lung and its remodeling in the context of disease or response to injury, gene expression must be activated and silenced in a coordinated manner to achieve the tremendous phenotypic heterogeneity of cell types required for homeostasis and pathogenesis. Epigenetic mechanisms, consisting of DNA base modifications such as methylation, alteration of histones resulting in chromatin modification, and the action of noncoding RNA, control the regulation of information "beyond the genome" required for both lung modeling and remodeling. Epigenetic regulation is subject to modification by environmental stimuli, such as oxidative stress, infection, and aging, and is thus critically important in chronic remodeling disorders such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), and pulmonary hypertension (PH). Technological advances have made it possible to evaluate genome-wide epigenetic changes (epigenomics) in diseases of lung remodeling, clarifying existing pathophysiological paradigms and uncovering novel mechanisms of disease. Many of these represent new therapeutic targets. Advances in epigenomic technology will accelerate our understanding of lung development and remodeling, and lead to novel treatments for chronic lung diseases.

PMID: 24789982 [PubMed - as supplied by publisher]

B-lines: Transthoracic chest ultrasound signs useful in assessment of interstitial lung diseases.

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B-lines: Transthoracic chest ultrasound signs useful in assessment of interstitial lung diseases.

Ann Thorac Med. 2014 4;9(2):99-103

Authors: Hasan AA, Makhlouf HA

Abstract
OBJECTIVE: This prospective study was conducted to evaluate the value of sonographic B-lines (previously called "comet tail artifacts"), which are long, vertical, well-defined, hyperechoic, dynamic lines originating from the pleural line in assessment of interstitial lung diseases (ILD) and compare them with the findings of chest high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs).
MATERIALS AND METHODS: Sixty-one patients with ILD underwent transthoracic lung ultrasound for assessment of the presence of B-lines and the distance between them. These findings were compared with that of chest HRCT (ground glass, reticular, nodular or honey combing) and PFT as forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO) and partial arterial oxygen pressure (PaO2).
RESULTS: All patients had diffuse bilateral B-lines. The distance between each of the two adjacent B lines correlated with the severity of the disease on chest HRCT where B3 (the distance was 3 mm) correlated with ground glass opacity and B7 (the distance was 7 mm) correlated with extensive fibrosis and honey combing. Also, the distance between B-lines inversely correlated with FVC (r = -0.848, P < 0.001), TLC (r = -0.664, P < 0.001), DLCO (r = -0.817, P < 0.001) and PaO2 (r = -0.902, P < 0.001).
CONCLUSION: B-lines that are lung Ultrasound signs seem to be useful in the assessment of ILD.

PMID: 24791173 [PubMed - as supplied by publisher]

Characterizing asthma from a drop of blood using neutrophil chemotaxis.

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Characterizing asthma from a drop of blood using neutrophil chemotaxis.

Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5813-8

Authors: Sackmann EK, Berthier E, Schwantes EA, Fichtinger PS, Evans MD, Dziadzio LL, Huttenlocher A, Mathur SK, Beebe DJ

Abstract
Asthma is a chronic inflammatory disorder that affects more than 300 million people worldwide. Asthma management would benefit from additional tools that establish biomarkers to identify phenotypes of asthma. We present a microfluidic solution that discriminates asthma from allergic rhinitis based on a patient's neutrophil chemotactic function. The handheld diagnostic device sorts neutrophils from whole blood within 5 min, and generates a gradient of chemoattractant in the microchannels by placing a lid with chemoattractant onto the base of the device. This technology was used in a clinical setting to assay 34 asthmatic (n = 23) and nonasthmatic, allergic rhinitis (n = 11) patients to establish domains for asthma diagnosis based on neutrophil chemotaxis. We determined that neutrophils from asthmatic patients migrate significantly more slowly toward the chemoattractant compared with nonasthmatic patients (P = 0.002). Analysis of the receiver operator characteristics of the patient data revealed that using a chemotaxis velocity of 1.55 μm/min for asthma yields a diagnostic sensitivity and specificity of 96% and 73%, respectively. This study identifies neutrophil chemotaxis velocity as a potential biomarker for asthma, and we demonstrate a microfluidic technology that was used in a clinical setting to perform these measurements.

PMID: 24711384 [PubMed - in process]

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