COPD, Smoking
Conditions
Keywords
Smoking, COPD, Non-Smokers, Smokers
Brief summary
We aim to use an integrated network systems approach to analyze certain existing small airway epithelium (SAE) omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomic levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease.
Detailed description
Hypothesis: We hypothesize that the disordered differentiation of the SAE that characterizes COPD results from the complex interaction of cigarette smoke components with a hierarchy of genetic, epigenetic, gene expression and metabolomics network interactions as the BC differentiate into a mucociliary epithelium. Specific aim 1. Using an integrated network systems approach to analyze our extensive existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomics levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease. Specific aim 2. To refine the model, a comprehensive omics data set will be collected at multiple time points as SAE BC of nonsmokers and COPD smokers differentiate to normal and disordered mucociliary epithelium (respectively) on air-liquid interface (ALI) culture, an in vitro model of SAE differentiation. The computational strategies from aim 1 will be used to improve the model with these data. Specific aim 3. To test and finalize the integrated network model, a parallel omics data set will be generated from BC from nonsmokers, and COPD smokers as they differentiate on ALI under conditions where key hubs will be up- or down-regulated and the differentiation process stressed under conditions mimicking the in vivo SAE environment. The end result will be an integrated systems model of SAE biology and how this is disordered in COPD.
Interventions
None listed
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Boehringer Ingelheim
Weill Medical College of Cornell University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy nonsmokers (n=50) Inclusion criteria * Must be enrolled into IRB approved protocol #1204012331(all inclusion criteria from protocol #1204012331 thus applies to this protocol) * Self-reported never-smokers, with current smoking status validated by the absence of nicotine metabolites in urine (nicotine less than 2 ng/ml and cotinine less than 5 ng/ml) * Negative HIV serology Smokers with COPD (n=50) Inclusion criteria * Must be enrolled into IRB approved protocol #1204012331(all inclusion criteria from protocol #1204012331 thus applies to this protocol) * Self-reported current daily smokers with greater than or equal to 10 pack-yr, validated by any of the following: urine nicotine greater than 30 ng/ml or urine cotinine greater than 50 ng/ml * Meeting GOLD stages I-III criteria for chronic obstructive lung disease (COPD) based on postbronchodilator spirometry * Taking any or no pulmonary-related medication, including beta-agonists, anticholinergics, or inhaled corticosteroids * Negative HIV serology Healthy nonsmokers (n=50)
Exclusion criteria
* Unable to meet the inclusion criteria (all
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of network pressure points relevant to SAE biology confirmed by analyze of SAE data sets. | One Year | Using an integrated network systems approach to analyze our extensive existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomics levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease. |
Countries
United States
Outcome results
None listed