Channing Chronic Obstructive Pulmonary Disease (COPD) Research

A Multidisciplinary Approach to Understand COPD Etiology, Heterogeneity, and Pathobiology to Improve Diagnosis, Prognosis and Treatment

COPD is a progressive lung disorder affecting more than 10 million Americans and millions more worldwide, where it is currently the third-leading cause of death.

Long-term exposure to lung irritants, with cigarette smoking as the dominant environmental risk factor, predisposes to COPD, but the response to irritants is highly variable. COPD is also a heterogeneous syndrome that includes destruction of the lung parenchyma (emphysema) and/or damage to small airways.

Current Research

Channing Division of Network Medicine (CDNM) investigators have built a comprehensive research strategy to:

• Study the epidemiology and progression of COPD
• Identify the genetic determinants of COPD
• Define key pathobiological mechanisms influencing COPD susceptibility and heterogeneity

We apply a multidisciplinary approach to understand COPD etiology, heterogeneity, and pathobiology to improve diagnosis and prognosis, and to develop therapeutics for treatment.

Achievements

Early research at Channing demonstrated the negative effects of secondhand tobacco smoke on lung growth and development, and subsequently showed that COPD aggregates in families, supporting the concept that genetic determinants influence COPD susceptibility.

Our research group has led many of the GWAS analyses of COPD and COPD-related phenotypes, and we are leading whole genome sequencing analysis of more than 12,000 subjects.

Genetics

Genetics is a crucial aspect of our research, including:

• Identifying COPD susceptibility loci using genome-wide association studies (GWAS) and whole genome sequencing
• Integrative analysis of multiple omics datasets (including gene expression and epigenetic marks)
• Imaging features from chest computed tomography

Network approaches

CDNM scientists model molecular interactions using complex network approaches, for example:

• Addressing complex disease heterogeneity by building COPD phenotypic networks
• Identifying COPD subtypes using networks
• Investigating the impact of sex in COPD manifestations and etiology from the point of view of gene regulatory networks

Study populations

Study populations developed by CDNM investigators include:

• COPD Gene Study, one of the largest studies in history to investigate the genetic factors of COPD
• Boston Early-Onset COPD Study, which examines environmental and genetic risk factors for the development of asthma and COPD
• ECLIPSE Study, a large population investigation examining COPD epidemiology and genetics
• International COPD Genetics Network
• National Emphysema Treatment Trial Genetics Ancillary Study

National and international collaborations

The Channing Division of Network Medicine leads collaborations with groups such as the American Thoracic Society, International COPD Genetics Consortium, NHLBI Trans-Omics in Precision Medicine (TOPMed), and others that allow us to access an extensive repertoire of multi-omics data.