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Clinical applications of gene-based risk prediction for lung cancer and the central role of chronic obstructive pulmonary disease.

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Clinical applications of gene-based risk prediction for lung cancer and the central role of chronic obstructive pulmonary disease.

Front Genet. 2012;3:210

Authors: Young RP, Hopkins RJ, Gamble GD

Abstract
Lung cancer is the leading cause of cancer death worldwide and nearly 90% of cases are attributable to smoking. Quitting smoking and early diagnosis of lung cancer, through computed tomographic screening, are the only ways to reduce mortality from lung cancer. Recent epidemiological studies show that risk prediction for lung cancer is optimized by using multivariate risk models that include age, smoking exposure, history of chronic obstructive pulmonary disease (COPD), family history of lung cancer, and body mass index. It has also been shown that COPD predates lung cancer in 65-70% of cases, conferring a four- to sixfold greater risk of lung cancer compared to smokers with normal lung function. Genome-wide association studies of smokers have identified a number of genetic variants associated with COPD or lung cancer. In a case-control study, where smokers with normal lungs were compared to smokers who had spirometry-defined COPD or histology confirmed lung cancer, several of these variants were shown to overlap, conferring the same susceptibility or protective effects on both COPD and lung cancer (independent of COPD status). In this perspective article, we show how combining clinical data with genetic variants can help identify heavy smokers at the greatest risk of lung cancer. Using this approach, we found that gene-based risk testing helped engage smokers in risk mitigating activities like quitting smoking and undertaking lung cancer screening. We suggest that such an approach could facilitate the targeted selection of smokers for cost-effective life-saving interventions.

PMID: 23087706 [PubMed]

The ACT and the ATAQ Are Useful Surrogates for Asthma Control in Resource-Poor Countries with Inadequate Spirometric Facilities.

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The ACT and the ATAQ Are Useful Surrogates for Asthma Control in Resource-Poor Countries with Inadequate Spirometric Facilities.

J Asthma. 2012 Oct 17;

Authors: Ozoh OB, Okubadejo NU, Chukwu CC, Bandele EO, Irusen EM

Abstract
Objective. The objective of this study is to determine the utility of simple asthma control questionnaires in assessing the asthma control in our practice setting. Methods. The Asthma Control Test (ACT), Asthma Therapy Assessment Questionnaire (ATAQ), and mini Asthma Quality of Life Questionnaire (mini AQLQ) were administered to previously diagnosed asthma patients. Spirometry was performed to obtain the prebronchodilator forced expiratory volume in 1 second (FEV1). The relationship between test scores (ACT and ATAQ) and the FEV1 and mini AQLQ scores, respectively, was explored. Results. A total of 106 patients (mean age 41 ± 15.3 years, 61 (57.5%) females) participated in the study. The mean ACT score was 17 ± 5.3 and the mean ATAQ score was 1.46 ± 1.34. There was a significant positive correlation between the ACT score and FEV1% predicted indicating the improvement in asthma control when FEV1% predicted increases (Pearson's correlation = 0.518, R(2) = 0.268, p < .0001) and a negative correlation between the ATAQ score and FEV1% predicted also indicating the improvement in asthma control when FEV1% predicted increases (Pearson's correlation = -0.516, R(2) = 0.266, p < .0001). The ACT score was significantly and positively related to the mini AQLQ score signifying an improvement in quality of life with increasing ACT score (Pearson's correlation = 0.691, R(2) = 0.461, p < .0001).The ATAQ score was significantly and negatively related to the mini AQLQ score indicating an improvement in quality of life with decreasing ATAQ score (Pearson's correlation = -0.654, R(2) = 0.428, p ≤ .0001). The FEV1% predicted and the mini AQLQ score were the only significant determinants of both the ACT score and the ATAQ score. Conclusion. The ACT and ATAQ are the objective and reliable tools in determining asthma control due to their strong correlation with the FEV1 and the asthma-specific health-related quality of life. Use of either questionnaire routinely will identify more patients with poor asthma control even when spirometry services are not readily available.

PMID: 23072262 [PubMed - as supplied by publisher]

Effects of tiotropium on lung function in severe asthmatics with or without emphysematous changes.

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Effects of tiotropium on lung function in severe asthmatics with or without emphysematous changes.

Pulm Pharmacol Ther. 2012 Oct 13;

Authors: Yoshida M, Nakano T, Fukuyama S, Matsumoto T, Eguchi M, Moriwaki A, Takata S, Machida K, Kanaya A, Matsumoto K, Nakanishi Y, Inoue H

Abstract
The effects of tiotropium, an inhaled long-acting anti-cholinergic agent, on lung function were investigated in obstructed severe asthmatics with and without emphysematous changes despite maximal recommended treatments with high-dose of inhaled glucocorticoids and inhaled long-acting β(2)-agonists. We conducted a double-blind, placebo-controlled study of an inhaled single-dose of tiotropium in 18 asthmatics with emphysema and 18 without emphysema in a crossover manner. The primary efficacy outcome was the relative change in forced expiratory volume in 1 s (FEV(1)) from baseline to 60 min, and the secondary outcome was a relative change in FEV(1) from baseline to 12 h. Subsequently, the patients were treated with tiotropium inhaled once daily for 12 weeks in an open label manner, and lung function and symptoms were evaluated. At baseline, patients with or without emphysema had a mean FEV(1) of 55.9% before tiotropium and 56.8% before placebo, or 77.4% before tiotropium and 77.6% before placebo of the predicted value and were taking a mean dose of inhaled glucocorticoids of 1444 or 1422 μg/day. Among patients with emphysema, the increase from baseline FEV(1) was 12.6 percentage points higher at 60 min after tiotropium than after placebo. Among patients without emphysema, the increase from baseline FEV(1) was 5.4 percentage points higher at 60 min after tiotropium than after placebo. Tiotropium resulted in improved lung function and symptoms in asthmatics with and without emphysema. These findings suggest that tiotropium will provide a new strategy for the treatment of bronchial asthma and of overlapping asthma and COPD.

PMID: 23073336 [PubMed - as supplied by publisher]

Assessing and accessing the small airways; implications for asthma management.

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Assessing and accessing the small airways; implications for asthma management.

Pulm Pharmacol Ther. 2012 Oct 13;

Authors: Scichilone N, Contoli M, Paleari D, Pirina P, Rossi A, Sanguinetti CM, Santus P, Sofia M, Sverzellati N

Abstract
Despite the wealth of experience in the management of asthma, the disease remains inadequately controlled in some patients, who face long-term respiratory impairment and disability. The disease has been characterised as an inflammatory condition affecting first the larger airways and eventually the smaller airways, but there is evidence that peripheral airway involvement defines a particular and more severe phenotype of asthma. For this reason, assessing functional and biological parameters reflective of small airways involvement is important prognostically. No assessment method is universally and directly representative of peripheral airway function, but the traditional spirometric tests, including vital capacity, residual volume and forced vital capacity, are somewhat correlated with this function; useful methods for further assessment include the single-breath nitrogen wash-out test, impulse oscillometry, nitrous oxide and exhaled breath concentrate measurements, as well as computed tomography to reflect air trapping and response to treatment. Formulation advancements have made for easier treatment access to the smaller airways, with the new extrafine formulations resulting in better asthma control compared with non-extrafine formulations.

PMID: 23073337 [PubMed - as supplied by publisher]

Vascular Endothelial Growth Factor as a Key Inducer of Angiogenesis in the Asthmatic Airways.

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Vascular Endothelial Growth Factor as a Key Inducer of Angiogenesis in the Asthmatic Airways.

Curr Allergy Asthma Rep. 2012 Oct 18;

Authors: Meyer N, Akdis CA

Abstract
Asthma is a chronic inflammatory disease of the airways characterized by structural airway changes, which are known as airway remodeling, including smooth muscle hypertrophy, goblet cell hyperplasia, subepithelial fibrosis, and angiogenesis. Vascular remodeling in asthmatic lungs results from increased angiogenesis, which is mainly mediated by vascular endothelial growth factor (VEGF). VEGF is a key regulator of blood vessel growth in the airways of asthma patients by promoting proliferation and differentiation of endothelial cells and inducing vascular leakage and permeability. In addition, VEGF induces allergic inflammation, enhances allergic sensitization, and has a role in Th2 type inflammatory responses. Specific inhibitors of VEGF and blockers of its receptors might be useful to control chronic airway inflammation and vascular remodeling, and might be a new therapeutic approach for chronic inflammatory airway disease like asthma.

PMID: 23076420 [PubMed - as supplied by publisher]

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