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Yang T.,Zhejiang Provincial CDC | Yang T.,University of California at Los Angeles | Chang P.-Y.,University of California at Los Angeles | Park S.L.,University of Hawaii at Manoa | And 11 more authors.
Cancer Causes and Control

Purpose: Although single nucleotide polymorphisms (SNPs) of NBS1 have been associated with susceptibility to lung and upper aerodigestive tract (UADT) cancers, their relations to cancer survival and measures of effect are largely unknown. Methods: Using follow-up data from 611 lung cancer cases and 601 UADT cancer cases from a population-based case-control study in Los Angeles, we prospectively evaluated associations of tobacco smoking and 5 NBS1 SNPs with all-cause mortality. Mortality data were obtained from the Social Security Death Index. We used Cox regression to estimate adjusted hazard ratios (HR) for main effects and ratios of hazard ratios (RHR) derived from product terms to assess hazard ratio variations by each SNP. Bayesian methods were used to account for multiple comparisons. Results: We observed 406 (66 %) deaths in lung cancer cases and 247 (41 %) deaths in UADT cancer cases with median survival of 1.43 and 1.72 years, respectively. Ever tobacco smoking was positively associated with mortality for both cancers. We observed an upward dose-response association between smoking pack-years and mortality in UADT squamous cell carcinoma. The adjusted HR relating smoking to mortality in non-small cell lung cancer (NSCLC) was greater for cases with the GG genotype of NBS1 rs1061302 than for cases with AA/AG genotypes (semi-Bayes adjusted RHR = 1.97; 95 % limits = 1.14, 3.41). Conclusions: A history of tobacco smoking at cancer diagnosis was associated with mortality among patients with lung cancer or UADT squamous cell carcinoma. The HR relating smoking to mortality appeared to vary with the NBS1 rs1061302 genotype among NSCLC cases. © 2013 Springer Science+Business Media Dordrecht. Source

Yeh G.Y.,Beth Israel Deaconess Medical Center | Wayne P.M.,Harvard University | Wayne P.M.,Brigham and Womens Hospital | Litrownik D.,Beth Israel Deaconess Medical Center | And 3 more authors.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic, progressively debilitating condition that is prevalent in the US and worldwide. Patients suffer from progressive dyspnea and exercise intolerance. Physical exercise is beneficial, but conventional pulmonary rehabilitation programs are underutilized. There remains a need for novel interventions that improve symptoms, quality-of-life, and functional capacity. Tai chi is an increasingly popular mind-body exercise that includes physical exercise, breathing training, mindful awareness, and stress management--components that are essential to the self-management of COPD. There are, however, limited data on the effectiveness of tai chi as a therapeutic intervention in this population.Methods/Design: The Primary Aims are to evaluate the efficacy, safety, and feasibility of a 12-week tai chi program for patients with COPD. We utilize a randomized controlled trial design, with participants assigned in a 2:1 ratio to either a group tai chi program (N = 63) or a time/attention-matched education control (N = 31). Our primary outcomes are COPD-specific quality-of-life and exercise capacity. Secondary outcomes include dyspnea, mood, functional status, self-efficacy, and lung function. Cardiopulmonary exercise testing is done in a subset of patients (N = 50). To explore optimal training duration, a subgroup of patients in tai chi are randomly assigned to complete an additional 12 weeks training (total 24 weeks) (Exploratory Aim 1). To explore the impact of a simplified seated intervention including only a subset of tai chi's training components, a third randomly assigned group (N = 31) receives a 12- week mind-body breathing program (N = 31) (Exploratory Aim 2).Discussion: Results of the BEAM study (Breathing, Education, Awareness, Movement) will provide preliminary evidence regarding the value of tai chi for improving quality of life and exercise capacity in patients with COPD, including information regarding optimal duration. They will also inform the feasibility and potential benefit of an alternative mind-body breathing intervention, and provide insight regarding how isolated mind-body exercise components contribute to the overall effects of tai chi. Should the results be positive, tai chi and related mind-body practices may offer a novel exercise option that is potentially accessible to a large proportion of patients with COPD.Trial registration: This trial is registered in Clinical Trials.gov, ID number NCT01551953. Date of Registration March 1 2012. © 2014 Yeh et al.; licensee BioMed Central Ltd. Source

Cowburn A.S.,University of Cambridge | Alexander L.E.C.,Pulmonary and Critical Care Section | Southwood M.,University of Cambridge | Nizet V.,University of California at San Diego | And 2 more authors.
Journal of Investigative Dermatology

Wound closure requires a complex series of micro-environmentally influenced events. A key aspect of wound closure is the migration of keratinocytes across the open wound. It has been found previously that the response to hypoxia via the HIF-1α transcription factor is a key feature of wound closure. The need for hypoxic response is likely due to interrupted wound vasculature, as well as infection, and in this work we investigated the need for a highly related hypoxic response transcription factor, HIF-2α. This factor was deleted tissue specifically in mice, and the resulting mice were found to have an accelerated rate of wound closure. This is correlated with a reduced bacterial load and inflammatory response in these mice. This indicates that manipulating or reducing the HIF-2α response in keratinocytes could be a useful means to accelerate wound healing and tissue repair. © 2014 The Society for Investigative Dermatology. Source

Akgun K.M.,Pulmonary and Critical Care Section | Akgun K.M.,Yale University | Crothers K.,University of Washington | Pisani M.,Yale University
Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Pulmonary disease prevalence increases with age and contributes to morbidity and mortality in older patients. Dyspnea in older patients is often ascribed to multiple etiologies such as medical comorbidities and deconditioning. Common pulmonary disorders are frequently overlooked as contributors to dyspnea in older patients. In addition to negative impacts on morbidity and mortality, quality of life is reduced in older patients with uncontrolled, undertreated pulmonary symptoms. The purpose of this review is to discuss the epidemiology of common pulmonary diseases, namely pneumonia, chronic obstructive pulmonary disease, asthma, lung cancer, and idiopathic pulmonary fibrosis in older patients. We will review common clinical presentations for these diseases and highlight differences between younger and older patients. We will also briefly discuss risk factors, treatment, and mortality associated with these diseases. Finally, we will address the relationship between comorbidities, pulmonary symptoms, and quality of life in older patients with pulmonary diseases. © 2011 The Author. Source

Tarleton H.P.,University of California at Los Angeles | Park S.L.,University of Hawaii at Manoa | Zhu W.-M.,University of California at Los Angeles | Lee Y.-C.A.,University of Utah | And 7 more authors.
International Journal of Cancer

Body mass index (BMI) has been inversely associated with lung and upper aerodigestive tract (UADT) cancers. However, only a few studies have assessed BMI change in adulthood in relation to cancer. To understand the relationship between BMI change and these cancers in both men and women, we analyzed data from a population-based case-control study conducted in Los Angeles County. Adulthood BMI change was measured as the proportional change in BMI between age 21 and 1 year before interview or diagnosis. Five categories of BMI change were included, and individuals with no more than a 5% loss or gain were defined as having a stable BMI (reference group). Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using logistic regression models. Potential confounders included age, gender, ethnicity, education, tobacco smoking and energy intake. For UADT cancers, we also adjusted for alcohol drinking status and frequency. A BMI gain of 25% or higher in adulthood was inversely associated with lung cancer (OR 0.53, 95% CI 0.33-0.84) and UADT cancers (OR 0.44, 95% CI 0.27-0.71). In subgroup analyses, a BMI gain of ≥25% was inversely associated with lung and UADT cancers among current and former smokers, as well as among current and former alcohol drinkers. The inverse association persisted among moderate and heavy smokers (≥20 pack-years). The observed inverse associations between adulthood BMI gain and lung and UADT cancers indicate a potential role for body weight-related biological pathways in the development of lung and UADT cancers. Copyright © 2011 UICC. Source

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