Asthma Randomized Trial of Indoor Wood Smoke (ARTIS): Rationale and Methods

Background—Particulate matter (PM) exposures have been linked with poor respiratory health outcomes, especially among susceptible populations such as asthmatic children. Smoke from biomass combustion for residential home heating is an important source of PM in many rural or peri-urban areas in the United States. Aim—To assess the efficacy of residential interventions that reduce indoor PM exposure from wood stoves and to quantify the corresponding improvements in quality of life and health outcomes for asthmatic children. Design—The Asthma Randomized Trial of Indoor wood Smoke (ARTIS) study is an in-home intervention study of susceptible children exposed to biomass combustion smoke. Children, ages 7 to 17, with persistent asthma and living in homes that heat with wood stoves were recruited for this three arm randomized placebo-controlled trial. Two household-level intervention strategies, wood stove replacement and air filters, were compared to a sham air filter placebo. Improvement in quality of life of asthmatic children was the primary outcomes. Secondary asthma-related health outcomes included peak expiratory flow (PEF) and forced expiratory volume in first second (FEV1), biomarkers in exhaled breath condensate, and frequency of asthma symptoms, medication usage, and healthcare utilization. Exposure outcomes included indoor and outdoor PM2.5 mass, particle counts of several size fractions, and carbon monoxide. Discussion—To our knowledge, this was the first randomized trial in the US to utilize interventions targeting residential wood stoves to assess the impact on indoor PM and health outcomes in a susceptible population. Trial registration—ClinicalTrials.gov NCT00807183

Biomass smoke exposures: Health outcomes measures and study design

Abstract Epidemiological studies of biomass smoke health effects have been conducted in a variety of settings and with a variety of study designs. The Health Effects Workgroup discussed several approaches for the investigation of health effects in communities exposed to wood smoke from nearby wildland fires, intentional agricultural burning, or residential biomass burning devices such as woodstoves or cookstoves. This presentation briefly reviews observational and intervention studies that have been conducted within these exposure settings. The review is followed by a summary of discussion points among the workgroup members with particular emphasis on study design and the use of biomarkers for assessing outcomes in biomass smoke-exposed populations

An Epigenetic Pilot Study Investigating Biomarkers in Maternal-Infant Pairs

Rationale: Particulate matter (PM) is a measurable component of air pollution that has been associated with adverse cardiovascular and respiratory outcomes. Research indicates environmental factors such as air pollution are involved in changes through epigenetic mechanisms during development that may persist into adulthood and even span multiple generations of inheritance. Epigenetics is the study of heritable changes of gene expression that do not alter the actual DNA sequence. One epigenetic mechanism is DNA methylation. Long Interspersed Nuclear Element (LINE-1) is a DNA repetitive element that can be used as a proxy measurement of DNA global methylation. The purpose of this pilot study was to compare epigenetic biomarkers across different sample matrices (i.e. blood and buccal) and across related subjects (i.e. maternal and infant). Methods: Informed consent was provided by pregnant women (n=23) who were recruited through Women, Infants, and Children (WIC), hospital birthing classes, or flyers in obstetrician’s offices. Demographic and medical data was collected from hospital records for both mothers and newborns after birth. Follow-up health surveys were administered by telephone that were designed to collect indicators of pre-asthmatic respiratory symptoms or conditions. Biological samples were collected before or shortly after time of birth at Community Medical Center of Missoula, MT. The samples collected were maternal blood (n=15), umbilical cord blood (n=15), and maternal (n=23) and newborn (n=23) buccal (cheek) cells. Buccal cells were collected and processed according to the Gentra Puregene Kit (Qiagen, Germantown, MD). These biologically accessible tissues serve as surrogates to study gene methylation associated with respiratory health. Samples were stored at -80°C until DNA extraction and subsequent bisulfite treatment. The samples were amplified in duplicates with polymerase chain reaction (PCR). LINE-1 methylation was analyzed with pyrosequencing on a Pyromark Q96 MD (Qiagen, Germantown, MD). All statistical analysis was performed in Statistical Analysis Software (SAS, version 9.3). Results: The mean (standard deviation (sd)) of LINE-1 methylation percentage for mother and infant buccal cell derived DNA were 58.75 (3.89) and 57.16 (2.54), respectively. Percent methylation maximum for mother and infant buccal samples were 70.22 and 64.25, respectively, and minimum were 54.86 and 52.94, respectively. Paired t-test indicated that LINE-1 methylation percentages in maternal buccal samples were higher than methylation percentages in the paired infant samples (mean difference (95%CL) = 4.4 (2.3, 6.6)). The mean (sd) of LINE-1 methylation percentage for mother and infant/cord blood derived DNA were 75.19 (3.17) and 75.86 (3.05), respectively. Percent methylation maximum for mother and infant blood samples were 79.42 and 79.50, respectively, and minimum were 70.39 and 69.31, respectively. Paired t-test indicated that LINE-1 methylation percentages in maternal blood samples were similar to methylation percentages in infant blood samples (mean difference (95% CL) = 0.66 (-2.0,3.3)). Conclusions: LINE-1 methylation percentages between sample matrices (i.e. blood and buccal) and subjects (i.e. maternal and infant) were not correlated. The percent methylation of LINE-1 in DNA from blood was consistently greater than for DNA from buccal tissue for both mother and newborn samples. It was expected that LINE-1 measurements for blood DNA would differ from buccal DNA because circulating blood represents a more diverse cell population. Gene-specific methylation of the promoter region for interferon-γ, a cytokine associated with asthma, will be studied with the remaining samples of bisulfite-treated DNA from this study. Epigenetic changes may serve as useful biomarkers for predicting asthma risk in children exposed to biomass smoke. These methods can be applied to future studies to investigate the epigenetic relationship of prenatal asthma risk and PM wood smoke exposure

Nested Case–Control Study of Autoimmune Disease in an Asbestos-Exposed Population

OBJECTIVE: To explore the potential association between asbestos exposure and risk of autoimmune disease, we conducted a case–control study among a cohort of 7,307 current and former residents of Libby, Montana, a community with historical occupational and environmental exposure to asbestos-contaminated vermiculite. METHODS: Cases were defined as those who reported having one of three systemic autoimmune diseases (SAIDs): systemic lupus erythematosus, scleroderma, or rheumatoid arthritis (RA). Controls were randomly selected at a 3:1 ratio from among the remaining 6,813 screening participants using frequency-matched age and sex groupings. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs) for SAIDs among those ≥ 65 years of age who had worked for the vermiculite mining company were 2.14 (95% CI, 0.90–5.10) for all SAIDs and 3.23 (95% CI, 1.31–7.96) for RA. In this age group, exposure to asbestos while in the military was also an independent risk factor, resulting in a tripling in risk. Other measures of occupational exposure to vermiculite indicated 54% and 65% increased risk for SAIDs and RA, respectively. Those who had reported frequent contact with vermiculite through various exposure pathways also demonstrated elevated risk for SAIDs and RA. We found increasing risk estimates for SAIDs with increasing numbers of reported vermiculite exposure pathways (p < 0.001). CONCLUSION: These preliminary findings support the hypothesis that asbestos exposure is associated with autoimmune disease. Refined measurements of asbestos exposure and SAID status among this cohort will help to further clarify the relationship between these variables

Air Toxics Under The Big Sky – A High School Science Teaching Tool

A project has been developed between Big Sky High School and The University of Montana (UM) which has brought together high school students and teachers, university scientists, and county environmental health officials in a multilayered research experience focusing on the collection and analysis of specific air toxics, and investigating their relationship to respiratory diseases. The Air Toxics Under the Big Sky project allows students to benefit from an independent experience linking science, research, and local environmental issues. We see this as a long term project which will be built upon and expanded by future students during each new school year and as new schools are added. This project will foster a long-term scientific collaboration between UM and Montana high schools, and establishes high school students as valuable contributors to the scientific community while educating them about environmental issues