RFG2

Environmental Lung Diseases

Dusty Secrets Could Help Asthma Sufferers

News Date: 
June 16, 2015 :00am

SWEHSC researchers, Fernando Martinez and  Donata Vercelli, who are members of the University of Arizona's BIO5 Institute have entered into a collaboration with Johnson & Johnson Consumer & Personal Products and Janssen Biotech Inc.

Society of Toxicology Award Recipient - Dr. Jefferey Burgess

Relevance to Swehsc : 

Dr. Jefferey Burgess is this year’s recipient of the Society of Toxicology Translation Impact Award.  The Award is presented to a scientist whose recent (last 10 years) outstanding clinical, environmental health or translational research has improved human and/or public health in an area of toxicological concern.

Cluster of Efforts: 

Scientists who are leaders in multidisciplinary team efforts that have contributed to alleviating toxicity-related health problems are particularly attractive candidates.  

Milestones: 

Dr. Burgess will be recognized at the Annual SOT meeting in San Diego in March, 2015 for his research on biomarker identification in arsenic exposed populations and on occupational inhalation exposures in fire fighters and miners.

CC16 and Chronic Lung Diseases

Relevance to Swehsc : 

Repression of CC16 by Cigarette Smoke (CS) Exposure. Zhu L, Di PY, Wu R, Pinkerton KE, Chen Y. PLoS One. 2015 Jan30;10(1):e0116159.doi: 10.1371/journal.pone.0116159. 

Cluster of Efforts: 

Club (Clara) Cell Secretory Protein (CCSP, or CC16) is produced mainly by non-ciliated airway epithelial cells including bronchiolar club cells and the change of its expression has been shown to associate with the progress and severity of Chronic Obstructive Pulmonary Disease (COPD). In an animal model, the lack of CC16 renders the animal susceptible to the tumorigenic effect of a major CS carcinogen. A recent population-based Tucson Epidemiological Study of Airway Obstructive Diseases (TESAOD) has indicated that the low serum CC16 concentration is closely linked with the smoke-related mortality, particularly that driven by the lung cancer. However, the study of CC16 expression in well-defined smoke exposure models has been lacking, and there is no experimental support for the potential causal link between CC16 and CS-induced pathophysiological changes in the lung. In the present study, we have found that airway CC16 expression was significantly repressed in COPD patients, in monkey CS exposure model, and in CS-induced mouse model of COPD. Additionally, the lack of CC16 exacerbated airway inflammation and alveolar loss in the mouse model. Therefore, CC16 may play an important protective role in CS-related diseases.

 

Article Published in International Journal of Environmental Research and Public Health

Relevance to Swehsc : 

Environmental arsenic exposure and microbiota in induced sputum. White AG, Watts GS, Lu Z, Meza-Montenegro MM, Lutz EA, Harber P, Burgess JL.  Int J Environ Res Public Health. 2014 Feb 21;11(2):2299-313. doi: 10.3390/ijerph110202299  

Cluster of Efforts: 

Arsenic exposure from drinking water is associated with adverse respiratory outcomes, but it is unknown whether arsenic affects pulmonary microbiota. This exploratory study assessed the effect of exposure to arsenic in drinking water on bacterial diversity in the respiratory tract of non-smokers. Induced sputum was collected from 10 subjects with moderate mean household water arsenic concentration (21.1 ± 6.4 ppb) and 10 subjects with low household water arsenic (2.4 ± 0.8 ppb). To assess microbiota in sputum, the V6 hypervariable region amplicons of bacterial 16s rRNA genes were sequenced using the Ion Torrent Personal Genome Machine. Microbial community differences between arsenic exposure groups were evaluated using QIIME and Metastats. A total of 3,920,441 sequence reads, ranging from 37,935 to 508,787 per sample for 316 chips after QIIME quality filtering, were taxonomically classified into 142 individual genera and five phyla. Firmicutes (22%), Proteobacteria (17%) and Bacteriodetes (12%) were the main phyla in all samples, with Neisseriaceae (15%), Prevotellaceae (12%) and Veillonellacea (7%) being most common at the genus level. Some genera, including Gemella, Lactobacillales, Streptococcus, Neisseria and Pasteurellaceae were elevated in the moderate arsenic exposure group, while Rothia, Prevotella, Prevotellaceae Fusobacterium and Neisseriaceae were decreased, although none of these differences was statistically significant. Future studies with more participants and a greater range of arsenic exposure are needed to further elucidate the effects of drinking water arsenic consumption on respiratory microbiota.

Article published in Journal of Exposure Science & Environmental Epidemiology

Relevance to Swehsc : 

Environmental Arsenic Exposure, Selenium and Sputum alpha-1 Antitrypsin

Cluster of Efforts: 

Significant decreases in alpha-1-antitrypsin were seen in induced sputum from adult populations exposed to low levels of arsenic in their drinking water (20 ppb).  Decreases in this enzyme have previously been associated with the development of chronic obstructive pulmonary disease and lung cancer. 

Drs. Vercelli & Snyder Collaborate on Asthma Protection in a Farm Environment

Relevance to Swehsc : 

A novel approach to the identification of asthma-protective environmental products from US farms.

Cluster of Efforts: 

During the past year, Dr. Vercelli engaged in an intense collaboration with SWEHSC member Dr. Shane Snyder on an EH project that aims at defining the compounds responsible for asthma protection in a farm environment and the underlying mechanisms. This collaboration, initially supported by a 2014 Pilot Project Award () to Drs. Vercelli and Snyder, led to the submission of a joint application to Johnson & Johnson, which has shown great interest in the translational potential of this project. The 2-year project (Asthma-protective mechanisms in the airways) and its budget were approved by the scientific arm of the company and discussions are now ongoing about details of the funding process. 

Milestones: 

Part of the preliminary data generated through the Pilot Project award supported Dr. Vercelli’s R01HL124988-01A1 submission titled "Differential Impact of US Farming Environments on Mechanisms of Asthma Risk".

MPIs: Ober, Vercelli; to be reviewin in March 2015

Low-Cost Air Sampling Method for Arsenic Exposure

Relevance to Swehsc : 

Use of dust fall filters as passive samplers for metal concentrations in air for communities near contaminated mine tailings.

Cluster of Efforts: 

Mine tailings are a source of metal exposures in many rural communities. Multiple air samples are necessary to assess the extent of exposures and factors contributing to these exposures. However, air sampling equipment is costly and requires trained personnel to obtain measurements, limiting the number of samples that can be collected. Simple, low-cost methods are needed to allow for increased sample collection. The objective of our study was to assess if dust fall filters can serve as passive air samplers and be used to characterize potential exposures in a community near contaminated mine tailings. We placed filters in cylinders, concurrently with active indoor air samplers, in 10 occupied homes. We calculated an estimated flow rate by dividing the mass on each dust fall filter by the bulk air concentration and the sampling duration. The mean estimated flow rate for dust fall filters was significantly different during sampling periods with precipitation. The estimated flow rate was used to estimate metal concentration in the air of these homes, as well as in 31 additional homes in another rural community impacted by contaminated mine tailings. The estimated air concentrations had a significant linear association with the measured air concentrations for beryllium, manganese and arsenic (p < 0.05), whose primary source in indoor air is resuspended soil from outdoors. In the second rural community, our estimated metal concentrations in air were comparable to active air sampling measurements taken previously. This passive air sampler is a simple low-cost method to assess potential exposures near contaminated mining sites.

 

 

Effect of Environmental Exposures to Arsenic

Relevance to Swehsc : 

Arsenic is a major environmental toxicant, not only in the Southwestern United States, but also throughout the world. Understanding the effects of inhaled arsenic in arid climates is particularly relevant.

Cluster of Efforts: 

Investigators: 

  • Jefferey Burgess, MD, MPH
  • Scott Boitano, PhD
  • Yin Chen, PhD
  • Margaret Kurzius-Spencer, PhD
  • R. Clark Lantz, PhD
Milestones: 
  • Significant decreases in a-1-antitrypsin were seen in induced sputum from adult populations exposed to low levels of arsenic in their drinking water. (Burgess, Boitano, Kurzius-Spencer, Lantz)
  • Children (ages 6-12) who have been exposed to arsenic in their drinking water during in utero and early life show decrements in lung function. (Lantz)
  • In utero and early postnatal inhalation exposure to real world dusts collected at a legacy mine site lead to alterations in lung function (increased airway reactivity). (Boitano, Lantz)
  • Arsenic Exposure through drinking water alters lung expression of genes and proteins involved in epithelial to mesenchymal transition (EMT). (Boitano, Lantz)
  • Animals exposed to arsenic have decreased expression levels of club (Clara) cell secretroy protein (CCSP). (Chen)

Exposure Assessment

Relevance to Swehsc : 

Accurarate determination of the sources and levels of exposure to environmental toxicants is essential to understanding the relationship between exposure and adverse health outcomes.

Cluster of Efforts: 

Investigators: 

  • Paloma Beamer, PhD
  • Jefferey Burgess, MD, MPH
  • Margaret Kurzius-Spencer, PhD
  • Fernando Martinez, MD
  • Mary Kay O'Rourke, PhD

 

Milestones: 
  • Analysis of dust fall down wind of a legacy mine site show that it is an excelent, low cost alternative for assessing dust related exposures. (Beamer)
  • Majority of inorganic and total arsenic exposure is attributable to diet in subjects with tap water arsenic <MCL. (Burgess, Kurzius-Spencer, O'Rourke)
  • Acute exposure to arsenic through ingestion of arsenic containg foods results in increased serum MMP-9 expression. (Burgess, Kurzius-Spencer, O'Rourke)
  • Wheezing lower respiratory infections were associated with increased air polution. (Beamer, Martinez)
  • CCSP levels are significantly decreased in children exposed to higher levels of diesel traffic-related air pollution. (Beamer, Chen)
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