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

NCT02220387 | Completed

• 2 other identifiers: 01201463369/101201463369
• Study Type: observational
• Target: 352
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

occupational COPD; phenotype; genetic

Outcome Measures

Primary Outcomes (13)

• Association of SNPs rs1800470 TGF β1 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 will be calculated for each occupational group. Controls - healthy people.

  1 day (a single measurement)

• Difference 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)

• Difference in serum interleukin 1 beta (IL-1β) level between COPD patients exposed to dust, chemicals and tobacco smoke.

  Comparison of groups.

  1 day (a single measurement)

• Difference in serum TNFα level between COPD patients exposed to dust, chemicals and tobacco smoke

  Comparison of groups.

  1 day (a single measurement)

• Difference in spontaneous thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke

  Comparison of groups.

  1 day (a single measurement)

• Difference in collagen induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke

  Comparison of groups.

  1 day (a single measurement)

• Difference in epinephrine induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke

  Comparison of groups.

  1 day (a single measurement)

• 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)

• Difference in fibrinogen level between COPD patients exposed to dust, chemicals and tobacco smoke

  Comparison of groups.

  1 day (a single measurement)

• Difference in fibrinogen degradation products level between COPD patients exposed to dust, chemicals and tobacco smoke

  Comparison of groups.

  1 day (a single measurement)

• Difference in D-dimer level between COPD patients exposed to dust, chemicals and tobacco smoke

  Comparison of groups.

  1 day (a single measurement)

• Difference in serum endothelin1 level between COPD patients exposed to dust, chemicals and tobacco smoke

  Comparison of groups.

  1 day (a single measurement)

• Difference in serum nitric oxide level between COPD patients exposed to dust, chemicals and tobacco smoke

  Comparison of groups.

  1 day (a single measurement)

Secondary Outcomes (1)

• Relationship between genotype and phenotype characteristics, such as an inflammation activity, assessed by hsCRP and TNF α serum concentration, in different occupational COPD groups.

  1 day (a single measurement)

Study Arms (2)

occupational COPD

Consists of 2 subgroups 1. COPD patients with history of exposure to respirable silica dust 2. COPD patients with history of exposure to polycyclic aromatic hydrocarbons exhaust

Other: exposure to respirable silica dust; Other: exposure to polycyclic aromatic hydrocarbons exhaust

smokers with COPD and healthy control

Consists of 2 subgroups 1. patients with COPD, history of tobacco smoke and no history of occupational exposure 2. healthy subjects

Interventions

exposure to respirable silica dust OTHER

History of exposure to respirable silica dust due to job

occupational COPD

exposure to polycyclic aromatic hydrocarbons exhaust OTHER

history of exposure to polycyclic aromatic hydrocarbons exhaust due to job

occupational COPD

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Residents of a certain town (Novosibirsk, Russian Federation)

You may qualify if:

• 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 absence of passive exposure to tobacco smoke or history of exposure to polycyclic aromatic hydrocarbons exhaust, nonsmokers with absence of passive exposure to 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
• Control group - healthy people

You may not qualify if:

• 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

Sponsors & Collaborators

• Novosibirsk City Hospital #2: lead
• Siberian Branch of the Russian Academy of Medical Sciences: collaborator

Study Sites (1)

Novosibirsk City Hospital #2

Novosibirsk, 630084, Russia

Location

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, serum,bronchoalveolar lavage fluid

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Liubov Shpagina, PhD

  Novosibirsk Citi Hospital #2, Novosibirsk State Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof., Dr

Study Record Dates

• First Submitted: August 11, 2014
• First Posted: August 19, 2014
• Study Start: August 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 6, 2015

Record last verified: 2015-10

Locations

RU (1)