The effect of motivational lung age feedback on short-term quit rates in smokers seeking intensive group treatment: A randomized controlled pilot study.

BACKGROUND: A brief "Lung Age" feedback intervention has shown promise for personalizing the health impact of smoking and promoting cessation in unselected smokers. Now that many healthcare organizations provide face-to-face cessation services, it is reasonable to ask whether such motivational feedback of lung function tests might improve treatment compliance and cessation rates in smokers wanting to quit. This study assessed effects of baseline motivational spirometry-based "Lung Age" feedback on treatment compliance and tobacco abstinence at 28-day follow-up. METHODS: This randomized controlled pilot study took place in Penn State University-affiliated outpatient medical practices. Participants were 225 adult smokers (≥5 cigarettes/day) willing to attend tobacco dependence treatment. At assessment lung function (FEV-1) and exhaled carbon-monoxide (CO) were assessed. The Intervention group (n=120) were randomly allocated to receive motivational "Lung Age" feedback estimated by FEV-1 and on exhaled CO; Control group (n=105) received minimal feedback. Participants were offered 6 weekly group smoking cessation sessions and nicotine patches and followed-up 28 days after target quit date. The primary outcome measure was self-reported 7-day tobacco abstinence, confirmed by CO<10ppm at 28-day follow-up. RESULTS: Quit rates were similar at follow-up (Intervention 50.8%; Control 52.4%; p=0.65) after controlling for abstinence predictors. Group attendance and patch use were similar. Among those attending follow-up (n=164, 73%), a greater proportion of the Intervention group had improved lung function (67% vs. 46%; p=0.0083). CONCLUSIONS: Baseline Lung Age feedback did not improve quit rates or compliance at 28-day follow-up in smokers seeking intensive treatment.

DNA methylation changes in the placenta are associated with fetal manganese exposure.

Adequate micronutrient intake, including manganese (Mn), is important for fetal development. Both Mn deficiencies and excess exposures are associated with later-life disease, and Mn accumulates in the placenta. Placental functional alterations may alter fetal programming and lifelong health, and we hypothesized that prenatal exposures to Mn may alter placental function through epigenetic mechanisms. Using Illumina's HumanMethylation450 BeadArray, DNA methylation of >485,000 CpG loci genome-wide was interrogated in 61 placental samples and Mn associations assessed genome-wide via omnibus test (p=0.045). 713 loci were associated with Mn exposure (p<0.0001). Five significantly differentially-methylated (p<1.3×10(-7)) loci reside in neurodevelopmental, fetal growth and cancer-related genes. cg22284422, within the uncharacterized LOC284276 gene, was associated with birth weight; for every 10% increase in methylation, lower birth weights were observed, with an average decrease of 293.44g. Our observations suggest a link between prenatal micronutrient levels, placental epigenetic status and birth weight, although these preliminary results require validation.

Novel DNA methylation targets in oral rinse samples predict survival of patients with oral squamous cell carcinoma.

OBJECTIVES: The objective of this study was to identify novel survival-associated biomarkers in oral rinse samples collected from patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: We screened for putative survival-associated markers using publicly available methylation array data from 88 OSCC tumors. Cox models were then fit to methylation array data restricted to these putative loci in oral rinse samples of 82 OSCC patients from greater Boston. Pyrosequencing assays were designed for each locus that replicated in the oral rinse samples and applied to a validation set of oral rinse samples from another 61 OSCC patients. RESULTS: We identified 7 survival-associated methylation markers in oral rinse samples from OSCC patients, and have validated one, located in the body of GABBR1, by pyrosequencing. CONCLUSION: The 7 CpG loci identified through this study represent novel prognostic biomarkers for patients with OSCC that can be detected using a non-invasive oral rinse collection technique.

Placental DNA methylation alterations associated with maternal tobacco smoking at the RUNX3 gene are also associated with gestational age.

AIMS: The developmental origins of health and disease hypothesis states that later-life disease may be influenced by the quality of the in utero environment. Environmental toxicants can have detrimental effects on fetal development, potentially through effects on placental development and function. Maternal smoking during pregnancy is associated with low birth weight, preterm birth and other complications, and exposure to cigarette smoke in utero has been linked to gross pathologic and molecular changes to the placenta, including differential DNA methylation in placental tissue. The aim of this study was to investigate the relationship between maternal smoking during pregnancy, methylation changes in the placenta and gestational age. MATERIALS & METHODS: We used Illumina(®)'s (CA, USA) Human Methylation27 BeadChip technology platform to investigate the methylation status of 21,551 autosomal, non-SNP-associated CpG loci in DNA extracted from 206 human placentas and examined loci whose variation in methylation was associated with maternal smoking during pregnancy. RESULTS: We found that methylation patterns of a number of loci within the RUNX3 gene were significantly associated with smoking during pregnancy, and one of these loci was associated with decreased gestational age (p = 0.04). CONCLUSION: Our findings, demonstrating maternal smoking-induced changes in DNA methylation at specific loci, suggest a mechanism by which in utero tobacco smoke exposure could exert its detrimental effects upon the health of the fetus.