Lung cancer and its association with chronic obstructive pulmonary disease: update on nexus of epigenetics.

Curr Opin Pulm Med. 2011 Apr 30;

Authors: Sundar IK, Mullapudi N, Yao H, Spivack SD, Rahman I

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) and lung cancer are the leading causes of morbidity and mortality worldwide. The current research is focused on identifying the common and disparate events involved in epigenetic modifications that concurrently occur during the pathogenesis of COPD and lung cancer. The purpose of this review is to describe the current knowledge and understanding of epigenetic modifications in pathogenesis of COPD and lung cancer. RECENT FINDINGS: This review provides an update on advances of how epigenetic modifications are linked to COPD and lung cancer, and their commonalities and disparities. The key epigenetic modification enzymes (e.g. DNA methyltransferases - CpG methylation, histone acetylases/deacetylases and histone methyltransferases/demethylases) that are identified to play an important role in COPD and lung tumorigenesis and progression are described in this review. SUMMARY: Distinct DNA methyltransferases and histone modification enzymes are differentially involved in pathogenesis of lung cancer and COPD, although some of the modifications are common. Understanding the epigenetic modifications involved in pathogenesis of lung cancer or COPD with respect to common and disparate mechanisms will lead to targeting of epigenetic therapies against these disorders.

PMID: 21537190 [PubMed - as supplied by publisher]

Efficacy of tiotropium in COPD patients from Asia: a subgroup analysis from the UPLIFT trial.

Respirology. 2011 May 3;

Authors: Fukuchi Y, Fernandez L, Kuo HP, Mahayiddin A, Celli B, Decramer M, Kesten S, Liu D, Tashkin D

SUMMARY AT A GLANCE: Sub-group analysis of Asian subjects with COPD enrolled in the international multi-centre UPLIFT trial demonstrates that this population benefits from treatment with inhaled tiotropium. For subjects receiving tiotropium, improvements were observed in lung function, exacerbation frequency, health-related quality of life and mortality. ABSTRACT: Background and objective:  Studies in respiratory diseases other than chronic obstructive pulmonary disease (COPD) suggest potentially differing responses to medications among patients from different regions. We report a subgroup analysis of patients recruited to Asian centres from a previously reported 4-year COPD trial. Methods:  Subgroup analysis from a randomised, double-blind, placebo-controlled trial of tiotropium 18 µg daily in COPD. Primary endpoint was rate of decline in forced expiratory volume in 1 second (FEV(1) ). Secondary endpoints included spirometry at individual time points, health-related quality of life (St George's Respiratory Questionnaire), exacerbations and mortality. Results:  Of 5992 patients, 362 were from Asian centres (100 from Japan). Mean age 66 years, 95% men, 13% current smokers, body mass index: 21 kg/m(2) ; post-bronchodilator FEV(1) : 44% predicted; St George's Respiratory Questionnaire total score: 44 units. No treatment effect was observed for rate of decline in FEV(1) although annual decline was less in Asian patients. Morning pre-bronchodilator FEV(1) and forced vital capacity improved in Asian patients (p < 0.05). Tiotropium reduced number of exacerbations (rate ratio [95% confidence interval (CI)]: 0.73 [0.57, 0.94]). Hazard ratios (95%I) for exacerbations and hospitalised exacerbations (tiotropium/control) were 0.81 (0.62, 1.05) and 0.85 (0.61, 1.19), respectively. St George's Respiratory Questionnaire total score improved by 1.5-6.1 units (p < 0.05 months 18, 24, 30 and 36) with tiotropium. Fatal events occurred in 34 tiotropium (18.5%) and 42 control (23.6%) patients. Conclusions:  In COPD patients from Asia, tiotropium improves lung function, improves health-related quality of life and reduces exacerbations over 4 years of treatment.

PMID: 21539680 [PubMed - as supplied by publisher]

Inspiratory muscle training in difficult to wean patients: work it harder, make it better, do it faster, makes us stronger.

Crit Care. 2011 Apr 18;15(2):153

Authors: Nava S, Fasano L

ABSTRACT: Weaning from prolonged mechanical ventilation is a complex, time-consuming process that involves the loss of force/generating capacity of the inspiratory muscle. In their study 'Inspiratory muscle strength training improves the outcome in failure to wean patients: a randomized trial', Martin and colleagues showed that the use of an inspiratory muscle strength program increased the maximal inspiratory pressure and improved weaning success compared to a control group. The study was performed mainly in post-surgical patients, however, and the results, therefore, may not be generalizable to other subsets of patients, such as those with chronic obstructive pulmonary disease or congestive heart failure. Indeed, the study applied so-called 'strength training' and not 'endurance training', which may be more appropriate in certain circumstances.

PMID: 21542873 [PubMed - as supplied by publisher]

Mechanisms of neutrophil transmigration across the vascular endothelium in COPD.

Thorax. 2011 May 4;

Authors: Gane J, Stockley R

Chronic obstructive pulmonary disease (COPD) is a common and important disease. Neutrophils have been shown to play a fundamental role in its development and progression. Understanding the mechanisms underlying the trafficking of neutrophils across the vascular endothelium into the lung could potentially allow the development of targeted biological treatments. The early stages of neutrophil tethering, adherence to and rolling on the endothelium have been determined. The later stages of diapedesis through the glycocalyx, endothelial cell (EC) layer and basement membrane, which are less well characterised, have been reviewed here. Evidence obtained from in vitro and in vivo work, concerning the implicated adhesion molecules on the neutrophil and endothelium, the mechanisms for neutrophil navigation through the EC junction (paracellular route) and evidence for transmigration through the body of an EC itself (transcellular route), is considered. The mechanisms are complex and are often disease and stimulus specific. There is evidence that a significant degree of redundancy occurs. Transmigration in the lung differs from that in other organs in that the neutrophil can exit the circulation either through the postcapillary venule in the systemic circulation or through the capillary in the pulmonary circulation. A number of factors make the mechanisms of transmigration within the lung and COPD model unique. These include physical differences between the flow through the capillary and the postcapillary venule, the modulating effect of the alveolar epithelium and other cells such as the macrophage, the presence of a 'diseased' neutrophil and indeed the presence or absence of acute, acute on chronic or chronic pulmonary disease.

PMID: 21543441 [PubMed - as supplied by publisher]