Molecular, Cytological Features and Genetic Susceptibility of COPD Attributable to Different Environmental Exposures 2

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

Molecular, Cytological Features and Genetic Susceptibility of Occupational Chronic Obstructive Pulmonary Disease Attributable to Different Environmental Exposures 2.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02284295
• Other study ID #: 01201463369/2
• Secondary ID: 01201463369
• Status: Completed
• Phase: N/A
• First received: November 3, 2014
• Last updated: April 13, 2015
• Start date: November 2014
• Est. completion date: November 2014

Study information

• Verified date: April 2015
• Source: Novosibirsk City Hospital #2
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: The Ministry of Education and Science of the Russian Federation
• Study type: Observational

Clinical Trial 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 fluid and association 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 alpha (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.

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 ATS endorsed the notion that strong evidence implicates occupational factors as cause of COPD. Occupational COPD takes 19.2 % of all COPD patients and 31.1 % of never smokers as resulted NHANESIII study. 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 aromatic hydrocarbons. Individuals in a variety of occupations and industries such as coal miners, painters, 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 we will use logistic regression method. The odds ratios (OR) and 95% confidence intervals (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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 352
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Post- bronchodilator forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio less than 0.7

• Stable phase of COPD

• History of exposure to respirable silica dust, nonsmokers with no of passive exposure of tobacco smoke or history of exposure to aromatic hydrocarbons, nonsmokers with no of passive exposure of tobacco smoke or current tobacco smokers without history of occupational exposure

• COPD risk factor exposure (occupational or tobacco smoke) duration not less than 12 months

• Male

• Caucasian

• Age of 40 - 75 years old

Exclusion Criteria:

• history of biomass smoke exposure

• age less than 40 and above 75 years old

• current COPD exacerbation

• concomitant asthma

• tuberculosis and other pulmonary diseases

• allergic and autoimmune disorders

• active infections

• immunodeficiency, including HIV infection

• parasitological diseases

• malignancies

• lack of informed consent.

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Disease Susceptibility
• Genetic Predisposition to Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Other:
• exposure to respirable silica dust
History of exposure to respirable silica dust due to job
• exposure to aromatic hydrocarbons
history of exposure to aromatic hydrocarbons due to job

Locations

Country	Name	City	State
Russian Federation	Novosibirsk City Hospital #2	Novosibirsk

Sponsors (2)

Lead Sponsor	Collaborator
Novosibirsk City Hospital #2	Siberian Branch of the Russian Academy of Medical Sciences

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in serum interleukin 1 beta (IL-1ß) level between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in serum tumor necrosis factor alpha (TNFa) level between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in spontaneous thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in collagen induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in epinephrine induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in adenosine diphosphate induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in fibrinogen level between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in fibrinogen degradation products level between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in D-dimer level between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in serum endothelin1 level between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Difference in serum nitric oxide level between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Differences in cytological analysis of bronchoalveolar lavage fluid results between COPD patients exposed to dust, chemicals and tobacco smoke	Comparison of groups	1 day (a single measurement)	No
Primary	Association of SNPs rs1800470 TGF ß1 gene, rs1828591 HHIP gene, rs4129267 IL-6R gene, rs1051730 CHRNA3 gene with COPD in subjects exposed to dust and in those exposed to chemicals. (Odds ratio and 95% confidence interval)	Odds ratio and 95% confidence interval will be calculated for each occupational group. Controls - healthy people.	1 day (a single measurement)	No
Secondary	Relationship between genotype and phenotype characteristics, such as an inflammation activity, assessed by hsCRP and TNF a serum concentration, in different occupational COPD groups.	For SNPs that will occur associated with occupational COPD differences in hsCRP and TNFa serum concentration between subjects with different genotypes will be established separately for exposed to dust COPD group and for exposed to chemicals COPD group.	1 day (a single measurement)	No