Feasibility of precision smoking treatment in a low-income community setting: results of a pilot randomized controlled trial in The Southern Community Cohort Study.

Background: The feasibility of precision smoking treatment in socioeconomically disadvantaged communities has not been studied.

Methods: Participants in the Southern Community Cohort Study who smoked daily were invited to join a pilot randomized controlled trial of three smoking cessation interventions: guideline-based care (GBC), GBC plus nicotine metabolism-informed care (MIC), and GBC plus counseling guided by a polygenic risk score (PRS) for lung cancer. Feasibility was assessed by rates of study enrollment, engagement, and retention, targeting > 70% for each.

Chr15q25 genetic variant (rs16969968) independently confers risk of lung cancer, COPD and smoking intensity in a prospective study of high-risk smokers.

Importance: While cholinergic receptor nicotinic alpha 5 (CHRNA5) variants have been linked to lung cancer, chronic obstructive pulmonary disease (COPD) and smoking addiction in case-controls studies, their corelationship is not well understood and requires retesting in a cohort study.

Objective: To re-examine the association between the CHRNA5 variant (rs16969968 AA genotype) and the development of lung cancer, relative to its association with COPD and smoking.

Methods: In 9270 Non-Hispanic white subjects from the National Lung Screening Trial, a substudy of high-risk smokers were followed for an average of 6.

Attitudes toward Precision Treatment of Smoking in the Southern Community Cohort Study.

Background: Precision interventions using biological data may enhance smoking treatment, yet are understudied among smokers who are disproportionately burdened by smoking-related disease.

Methods: We surveyed smokers in the NCI-sponsored Southern Community Cohort Study, consisting primarily of African-American, low-income adults. Seven items assessed attitudes toward aspects of precision smoking treatment, from undergoing tests to acting on results.

Mevalonate signaling, COPD and cancer: the statins and beyond.

Evidence suggests that smoking confers a persistent and/or exaggerated inflammatory response in the lungs that, with underlying genetic susceptibility, may result in lung remodeling and impaired repair. The innate immune response to smoking described above, which is modified by the mevalonate pathway, provides a plausible pathogenic link between the development of chronic obstructive pulmonary disease and lung cancer. The mevalonate pathway modifies innate responsiveness through important intracellular signaling molecules called guanine phosphate transferases (GTPases) such as Rho-A.

Chronic obstructive pulmonary disease (COPD) and lung cancer screening.

The primary aim of lung cancer screening is to improve survival from lung cancer by identifying early stage non-small cell lung cancers and prolong survival through their surgical removal. In a analysis of 10,054 screening participants from the National Lung Screening Trial (NLST) we show that the risk of lung cancer, according to the PLCOm2012 model, is closely related to the likelihood of having chronic obstructive pulmonary disease (COPD). Those at greatest risk for lung cancer have the highest prevalence of COPD and greater likelihood of dying of a non-lung cancer cause.

Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial-American College of Radiology Imaging Network Cohort.

Rationale: Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk.

Objectives: We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4.

Incorporating epistasis interaction of genetic susceptibility single nucleotide polymorphisms in a lung cancer risk prediction model.

Incorporation of genetic variants such as single nucleotide polymorphisms (SNPs) into risk prediction models may account for a substantial fraction of attributable disease risk. Genetic data, from 2385 subjects recruited into the Liverpool Lung Project (LLP) between 2000 and 2008, consisting of 20 SNPs independently validated in a candidate-gene discovery study was used. Multifactor dimensionality reduction (MDR) and random forest (RF) were used to explore evidence of epistasis among 20 replicated SNPs.

The Mevalonate Pathway and Innate Immune Hyper-Responsiveness in the Pathogenesis of COPD and Lung Cancer: Potential for Chemoprevention.

Current evidence suggests that persisting and/or exaggerated inflammation in the lungs initiated by smoking, and up-regulated through genetic susceptibility, may result in lung remodelling and impaired repair. The mevalonate pathway, through its modifying effects on innate immune responsiveness, may be involved in these processes providing a plausible pathogenic link between the development of chronic obstructive pulmonary disease (COPD) and lung cancer. The mevalonate pathway, mediates these effects through important intra-cellular signalling molecules called guanine phosphate transferases (GTPases) such as Rho-A.

The Gut-Liver-Lung Axis. Modulation of the Innate Immune Response and Its Possible Role in Chronic Obstructive Pulmonary Disease.

Evidence from epidemiological studies suggests that a diet high in fiber is associated with better lung function and reduced risk of chronic obstructive pulmonary disease (COPD). The mechanism for this benefit remains unknown, but, as fiber is not absorbed by the gut, this finding suggests that the gut may play an active role in pathogenic pathways underlying COPD. There is a growing awareness that aberrant activity of the innate immune system, characterized by increased neutrophil and macrophage activation, may contribute to the development or progression of COPD.

Airflow Limitation and Histology Shift in the National Lung Screening Trial. The NLST-ACRIN Cohort Substudy.

Rationale: Annual computed tomography (CT) is now widely recommended for lung cancer screening in the United States, although concerns remain regarding the potential harms, including those from overdiagnosis.

Objectives: To examine the effect of airflow limitation on overdiagnosis by comparing lung cancer incidence, histology, and stage shift in a subgroup of the National Lung Screening Trial (NLST).

Methods: In an NLST subgroup (n = 18,714), screening participants were randomized to annual computed tomography (CT, n = 9,357) or chest radiograph (n = 9,357) screening and monitored for a mean of 6.

A review of the Hispanic paradox: time to spill the beans?

Past epidemiological observations and recent molecular studies suggest that chronic obstructive pulmonary disease (COPD) and lung cancer are closely related diseases, resulting from overlapping genetic susceptibility and exposure to aero-pollutants, primarily cigarette smoke. Statistics from the American Lung Association and American Cancer Society reveal that mortality from COPD and lung cancer are lowest in Hispanic subjects and generally highest in African American subjects, with mortality in non-Hispanic white subjects and Asian subjects in between. This observation, described as the “Hispanic paradox”, persists after adjusting for confounding variables, notably smoking exposure and sociodemographic factors.