Epidemiologic evidence for asthma and exposure to air toxics: linkages between occupational, indoor, and community air pollution research.

Outdoor ambient air pollutant exposures in communities are relevant to the acute exacerbation and possibly the onset of asthma. However, the complexity of pollutant mixtures and etiologic heterogeneity of asthma has made it difficult to identify causal components in those mixtures. Occupational exposures associated with asthma may yield clues to causal components in ambient air pollution because such exposures are often identifiable as single-chemical agents (e.g., metal compounds). However, translating occupational to community exposure-response relationships is limited. Of the air toxics found to cause occupational asthma, only formaldehyde has been frequently investigated in epidemiologic studies of allergic respiratory responses to indoor air, where general consistency can be shown despite lower ambient exposures. The specific volatile organic compounds (VOCs) identified in association with occupational asthma are generally not the same as those in studies showing respiratory effects of VOC mixtures on nonoccupational adult and pediatric asthma. In addition, experimental evidence indicates that airborne polycyclic aromatic hydrocarbon (PAH) exposures linked to diesel exhaust particles (DEPs) have proinflammatory effects on airways, but there is insufficient supporting evidence from the occupational literature of effects of DEPs on asthma or lung function. In contrast, nonoccupational epidemiologic studies have frequently shown associations between allergic responses or asthma with exposures to ambient air pollutant mixtures with PAH components, including black smoke, high home or school traffic density (particularly truck traffic), and environmental tobacco smoke. Other particle-phase and gaseous co-pollutants are likely causal in these associations as well. Epidemiologic research on the relationship of both asthma onset and exacerbation to air pollution is needed to disentangle effects of air toxics from monitored criteria air pollutants such as particle mass. Community studies should focus on air toxics expected to have adverse respiratory effects based on biological mechanisms, particularly irritant and immunological pathways to asthma onset and exacerbation

Genome Wide Association Study to predict severe asthma exacerbations in children using random forests classifiers

<p>Abstract</p> <p>Background</p> <p>Personalized health-care promises tailored health-care solutions to individual patients based on their genetic background and/or environmental exposure history. To date, disease prediction has been based on a few environmental factors and/or single nucleotide polymorphisms (SNPs), while complex diseases are usually affected by many genetic and environmental factors with each factor contributing a small portion to the outcome. We hypothesized that the use of random forests classifiers to select SNPs would result in an improved predictive model of asthma exacerbations. We tested this hypothesis in a population of childhood asthmatics.</p> <p>Methods</p> <p>In this study, using emergency room visits or hospitalizations as the definition of a severe asthma exacerbation, we first identified a list of top Genome Wide Association Study (GWAS) SNPs ranked by Random Forests (RF) importance score for the CAMP (Childhood Asthma Management Program) population of 127 exacerbation cases and 290 non-exacerbation controls. We predict severe asthma exacerbations using the top 10 to 320 SNPs together with age, sex, pre-bronchodilator FEV1 percentage predicted, and treatment group.</p> <p>Results</p> <p>Testing in an independent set of the CAMP population shows that severe asthma exacerbations can be predicted with an Area Under the Curve (AUC) = 0.66 with 160-320 SNPs in comparison to an AUC score of 0.57 with 10 SNPs. Using the clinical traits alone yielded AUC score of 0.54, suggesting the phenotype is affected by genetic as well as environmental factors.</p> <p>Conclusions</p> <p>Our study shows that a random forests algorithm can effectively extract and use the information contained in a small number of samples. Random forests, and other machine learning tools, can be used with GWAS studies to integrate large numbers of predictors simultaneously.</p

Systematic review of the evidence relating FEV1 decline to giving up smoking

<p>Abstract</p> <p>Background</p> <p>The rate of forced expiratory volume in 1 second (FEV₁) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta.</p> <p>Methods</p> <p>Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors.</p> <p>Results</p> <p>Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex.</p> <p>Conclusion</p> <p>The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV₁decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.</p

Accelerated Partial Breast Irradiation (APBI): A review of available techniques

Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified

A Cohort Study of the Impact of Tooth Loss and Periodontal Disease on Respiratory Events among COPD Subjects: Modulatory Role of Systemic Biomarkers of Inflammation

BACKGROUND: In COPD patients, fatal and non-fatal respiratory-related events are influenced by age, severity of respiratory disease, and comorbidities. OBJECTIVES: Analyze the effects of edentulism, periodontal disease and systemic biomarkers of inflammation on the occurrence of serious fatal and non-fatal respiratory-related events among subjects with COPD. METHODS: Cases were identified from Dental Atherosclerosis Risk in Communities study. Edentulism was defined as study participants without any natural teeth or implants. Participants with one or more natural teeth (comprising 11,378 subjects) were studied as dentate subjects. Periodontal disease status among dentate individuals was determined using the consensus definitions published by the joint Center for Disease Control/American Association of Periodontology working group). Adjusted Hazard Models are developed to evaluate the relationship between edentulism/periodontal disease and COPD Related Events. Models were then stratified by GOLD Stage I, II and III/IV. Serum biomarkers were also evaluated to explore the effect of systemic inflammation. RESULTS: A statistically significant association was found between oral health status and COPD-related events, even adjusting for conditions such as hypertension, smoking and diabetes. Edentulous individuals who had been diagnosed with COPD had a higher incidence and were at greater risk of having a COPD related event (hospitalization and death) than individuals who had teeth and whose mouths had healthy periodontal status. However, being edentulous did not convey excess risk for COPD-related events for those study participants who were classified as GOLD III/IV at baseline. Finally, we showed that individuals who had levels of serum IL-6 in the highest two quartiles were at even higher risk for COPD-related events. CONCLUSIONS: These findings suggest that the risk for COPD-related events after adjusting for potential confounders may be attributable to both edentulism and elevated serum IL-6 levels