Updated systematic review of the effects of exercise on understudied health outcomes in cancer survivors

Abstract Introduction The American College of Sports Medicine provided guidelines for exercise prescriptions in cancer survivors for specific cancer‐ and treatment‐related health outcomes. However, there was insufficient evidence to generate exercise prescriptions for 10 health outcomes of cancer treatment. We sought to update the state of evidence. Methods We conducted a systematic review of these 10 understudied health outcomes (bone health, sleep, cardiovascular function, chemotherapy‐induced peripheral neuropathy (CIPN), cognitive function, falls and balance, nausea, pain, sexual function, and treatment tolerance) and provided an update of evidence. Results While the evidence base for each outcome has increased, there remains insufficient evidence to generate exercise prescriptions. Common limitations observed across outcomes included: variability in type and quality of outcome measurement tools, variability in definitions of the health outcomes, a lack of phase III trials, and a majority of trials investigating breast or prostate cancer survivors only. Conclusion We identified progress in the field of exercise oncology for several understudied cancer‐ and treatment‐related health outcomes. However, we were not able to generate exercise prescriptions due to continued insufficient evidence base. More work is needed to prescribe exercise as medicine for these understudied health outcomes, and our review highlights several strategies to aid in research acceleration within these areas of exercise oncology

Time to First Morning Cigarette and Risk of Chronic Obstructive Pulmonary Disease: Smokers in the PLCO Cancer Screening Trial

<div><p>Background</p><p>Time to first cigarette (TTFC) after waking is an indicator of nicotine dependence. The association between TTFC and chronic obstructive pulmonary disease (COPD), the third leading cause of death in the United States, has not yet been reported.</p><p>Methods</p><p>We investigated the cross-sectional association between TTFC and prevalent COPD among 6,108 current smokers in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. COPD was defined as a self-reported diagnosis of emphysema, chronic bronchitis, or both. Current smokers in PLCO reported TTFC, the amount of time they typically waited before smoking their first cigarette of the day after waking, in four categories: ≤5, 6-30, 31-60, or >60 minutes. We used logistic regression models to investigate the association between TTFC and prevalent COPD with adjustments for age, gender, race, education, and smoking (cigarettes/day, years smoked during lifetime, pack-years, age at smoking initiation), and prior lung cancer diagnosis.</p><p>Results</p><p>COPD was reported by 19% of these 6,108 smokers. Individuals with the shortest TTFC had the greatest risk of COPD; compared to those with the longest TTFC (>60 minutes) the adjusted odds ratios (OR) and 95% confidence intervals (CI) for COPD were 1.48 (95% CI, 1.15-1.91), 1.64 (95% CI, 1.29-2.08), 2.18 (95% CI, 1.65-2.87) for those with TTFC 31-60 minutes, 6-30 minutes, and ≤5 minutes, respectively (P-trend <0.0001). The association between TTFC and emphysema was similar to that for bronchitis, albeit the ORs were slightly stronger for chronic bronchitis; comparing TTFC ≤5 minutes to >60 minutes, the adjusted OR (95% CI) was 2.29 (1.69-3.12) for emphysema and 2.99 (1.95-4.59) for chronic bronchitis.</p><p>Conclusions</p><p>Current smokers with shorter TTFC have increased risk of COPD compared to those with longer TTFC, even after comprehensive adjustment for established smoking covariates. Future epidemiologic studies, including prospective designs, should incorporate TTFC to better assess disease risk and evaluate the potential utility of TTFC as a COPD screening tool for smokers in the clinical setting.</p></div

Effect of long-term vitamin E and selenium supplementation on urine F2-isoprostanes, a biomarker of oxidative stress

BackgroundCigarette smoking generates reactive oxidant species and contributes to systemic oxidative stress, which plays a role in the pathophysiology of chronic diseases. Nutrients with antioxidant properties, including vitamin E and selenium, are proposed to reduce systemic oxidative burden and thus to mitigate the negative health effects of reactive oxidant species.ObjectiveOur objective was to determine whether long-term supplementation with vitamin E and/or selenium reduces oxidative stress in smokers, as measured by urine 8-iso-prostaglandin F2-alpha (8-iso-PGF2α).DesignWe measured urine 8-iso-PGF2α with competitive enzyme linked immunoassay (ELISA) in 312 male current smokers after 36 months of intervention in a randomized placebo-controlled trial of vitamin E (400IU/d all rac-α-tocopheryl acetate) and/or selenium (200µg/d L-selenomethionine). We used linear regression to estimate the effect of intervention on urine 8-iso-PGF2α, with adjustments for age and race.ResultsCompared to placebo, vitamin E alone lowered urine 8-iso-PGF2α by 21% (p=0.02); there was no effect of combined vitamin E and selenium (intervention arm lower by 9%; p=0.37) or selenium alone (intervention arm higher by 8%; p=0.52).ConclusionsLong-term vitamin E supplementation decreases urine 8-iso-PGF2α among male cigarette smokers, but we observed little to no evidence for an effect of selenium supplementation, alone or combined with vitamin E

Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults.

Metabolomic markers associated with incident central adiposity gain were investigated in young adults. In a 9-mo prospective study of university freshmen (n = 264). Blood samples and anthropometry measurements were collected in the first 3 d on campus and at the end of the year. Plasma from individuals was pooled by phenotype [incident central adiposity, stable adiposity, baseline hemoglobin A1c (HbA1c) > 5.05%, HbA1c 5.05% had 21-fold (95% CI: 19.84, 21.41) higher blood erythritol compared with participants with lower HbA1c (P < 0.001, FDR = 0.00016). Erythritol was shown to be synthesized endogenously from glucose via the pentose-phosphate pathway (PPP) in stable isotope-assisted ex vivo blood incubation experiments and through in vivo conversion of erythritol to erythronate in stable isotope-assisted dried blood spot experiments. Therefore, endogenous production of erythritol from glucose may contribute to the association between erythritol and obesity observed in young adults

Adjusted Odds Ratio for COPD according to Time to First Cigarette (TTFC) among current smokers in PLCO.

<p>COPD cases responded affirmatively to question(s) regarding diagnosis of emphysema (on study baseline questionnaire, follow-up questionnaire in 2006, or both), chronic bronchitis (on study baseline questionnaire), or both. ORs and 95% CIs were determined using logistic regression with adjustments for age, gender (except in gender-stratified analyses), race, education, cigarettes/day, years smoked during lifetime, pack-years, age at smoking initiation, and lung cancer diagnosis prior to follow-up questionnaire. TTFC was categorical (>60 minutes as reference) with the exception of P-trend assessment where TTFC was treated as an ordinal variable.</p><p>PLCO, Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. P-value for interaction between TTFC*gender interaction term. Significant P-values (P<0.05) in bold.</p><p>^a N = 6,106; 2 participants were excluded due to missing data on emphysema endpoint.</p><p>^b N = 6,070; 38 participants were excluded due to missing data on bronchitis endpoint.</p><p>Adjusted Odds Ratio for COPD according to Time to First Cigarette (TTFC) among current smokers in PLCO.</p

Characteristics of Current Smokers in the PLCO Study, by COPD Status.

<p>COPD cases responded affirmatively to question(s) regarding diagnosis of emphysema (on study baseline questionnaire, follow-up questionnaire in 2006, or both), chronic bronchitis (on study baseline questionnaire), or both. Baseline data were substituted for missing follow-up questionnaire data for the following variables (number of participants) for race (218), age at smoking initiation (108), pack-years (299), cigarettes per day (65), smoking duration (262). PLCO, Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Some values do not sum to 100 due to missing data.</p><p>^a Report prior to PLCO follow-up questionnaire in 2006</p><p>^b Self-report of emphysema and chronic bronchitis was not mutually exclusive; 201 participants reported a diagnosis of both emphysema and chronic bronchitis, thus the sum of reports of emphysema and chronic bronchitis are greater than the total 1,136 COPD cases.</p><p>Characteristics of Current Smokers in the PLCO Study, by COPD Status.</p

Time to first cigarette (TTFC) upon waking and risk of chronic obstructive pulmonary disease (COPD) among current smokers.

<p>Odds Ratios for each category of TTFC (≤5, 6–30, and 31–60 minutes, compared to the reference group of smokers with TTFC >60 minutes) were calculated by logistic regression, adjusted for age, gender (except in gender-stratified analyses), race, education, cigarettes/day, years smoked during lifetime, pack-years, age at smoking initiation, and lung cancer diagnosis prior to follow-up questionnaire. (A) OR for COPD, emphysema, and chronic bronchitis. (B) OR for COPD by age at smoking initiation. (C) OR for COPD by typical number of cigarettes smoked per day. (D) OR for COPD by pack-years. (E) OR for COPD by total smoking duration in years. Categories of smoking covariates were collapsed for visual representation of results; refer to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125973#pone.0125973.t002" target="_blank">Table 2</a> for further details.</p