Molecular, Cytological Features and Genetic Susceptibility of COPD Attributable to Different Environmental Exposures
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Genetic Predisposition to Disease
Study type: Observational

Summary: 
      The objective of this study is to investigate molecular, cytological and genetic features of
      occupational chronic obstructive pulmonary disease (COPD) in conditions of different
      occupational exposures. In order to achieve this goal serum pro-inflammatory cytokines and
      standard inflammation markers level, hemostasis, cytological analysis of bronchoalveolar
      lavage and associations of single nucleotide polymorphisms (SNPs) rs1800470 transforming
      growing factor β1 (TGF β1) gene, rs1828591 hedgehog interacting protein (HHIP) gene,
      rs4129267 interleukin 6 receptor (IL-6R) gene, rs1051730 nicotinic acetylcholine receptor 3
      (CHRNA3) gene with COPD in subjects exposed to silica dust and in those exposed to polycyclic
      aromatic hydrocarbons exhaust will be investigated. The relationship between genotype and
      phenotype characteristics, such as an inflammation activity, assessed by C-reactive protein
      (hsCRP) and tumor necrosis factor-α (TNF α) serum concentration, in different occupational
      COPD groups will be studied. The hypothesis is that the mechanisms underlying disease
      development and progression are different due to environmental risk factor that reflex in
      differs in disease attributes - molecular biomarkers, cytology results and genetic
      susceptibility between COPD due to dust, COPD due to chemicals and COPD in smokers therefore
      COPD can be subdivided into ecological phenotypes according to environmental risk factor.
    

Detailed description: 
      Study rationale: The main risk factors of COPD are tobacco smoking, biomass smoking and
      occupational factors. Tobacco smoking is well-known risk factor so tobacco induced COPD is
      completely established. Nevertheless the meaning of occupational factors which are less
      famous are equally important. Based on comprehensive literature review American Thoracic
      Society (ATS) endorsed the notion that strong evidence implicates occupational factors as
      cause of COPD [Eisner MD et al., 2010]. Occupational COPD takes 19.2 % of all COPD patients
      and 31.1 % of never smokers as resulted NHANESIII study [Hnizdo E. et al., 2004]. A
      considerable number of work-related factors have evidence for a causal association with COPD
      including (and of course not limited) silica and silicates and polycyclic aromatic
      hydrocarbons. Individuals in a variety of occupations and industries such as coal miners,
      coke workers, tunnel workers, metallurgists, welding workers, transportation workers,
      builders, farmers are exposed to factors cited above. Despite this the clinical and
      pathophysiological features of COPD caused by occupational factors are still unclear.

      Occupational factors leading airflow limitation are various entities - vapors, dusts, gases
      and fumes with different physical, chemical, biological and other features, so the mechanisms
      underlying disease development and progression may be different attributable to risk factor.

      An environmental risk factors exposure as well as tobacco smoking results in COPD only in
      part of the subjects which indicates the significant genome and gene environmental
      interactions role. COPD develops in predisposed subjects undergoing risk factors exposure.
      Therefore the risk of COPD is individual and depends on both genetic and environments. There
      are few data concerning the effects of genetic on COPD risk in this specific subgroup -
      people who are exposed to occupational risk factors related to the certain environmental
      factor.

      Statistical analysis: Statistical analysis will be carried out by Statistica 9.0 software.
      Significance level will be considered p = 0.05. The qualitative variables will be expressed
      as counts and percentages. The quantitative continuous variables will be expressed as means
      and standard error of means (M ± m) for variables that meet the criteria of normality and
      minimum and maximum, median for those that do not meet the criteria of normality.
      Kruskal-Wallis test will be used for comparing multiply independent samples and Mann-Whitney
      U test for comparing two independent samples if variable under consideration will continuous
      and that it will be measured on an ordinal scale. For comparisons of proportions, the
      Chi-square will be used.

      For associations assessment logistic regression method will be used. The odds ratio (OR) and
      95% confidence interval (CI) will be calculated for each professional group. Multiple
      regression model will be used to explore the relationships between demographic
      characteristics, cytokine concentrations, hemostasis and airflow limitation in professional
      groups.
    

Intervention name(s): exposure to respirable silica dust; exposure to polycyclic aromatic hydrocarbons exhaust
Intervention type(s): Other; Other
Intervention description(s): History of exposure to respirable silica dust due to job; history of exposure to polycyclic aromatic hydrocarbons exhaust due to job
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Residents of a certain town (Novosibirsk, Russian Federation)
      
Biospecimen description: 
      whole blood, serum,bronchoalveolar lavage fluid
    
Keywords: occupational COPD; phenotype; genetic