The role of epigenetic modifications in COPD

Seeking answers to the biomarkers of Chronic obstructive pulmonary disease (COPD), an irreversible lung disease.

Epigenetic modifications of COPD, a lung disease that involves shortness of breath.


Research background

Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible lung disease characterised by recurrent cough, shortness of breath and increased sputum production.

The most common conditions that contribute to COPD are chronic bronchitis and emphysema with the relative contribution of each condition varying among patients. Tobacco smoking, either actively or through second hand smoke, is a primary risk factor in the development of COPD.

There is a serious need to identify better and more individual based diagnostic tools for COPD. It is clear from previous research that COPD is heterogeneous, with highly variable symptoms among patients. It is also marked by epigenetic changes, some of which have been associated with COPD phenotypes.

Identifying these key epigenetic biomarkers and their biological significance in early stage COPD will ensure that the disease is properly managed, and that patients have a better quality of life.

Also, associating disease course and progression with these epigenetic patterns is also essential to providing the right and precise therapeutic intervention.

Research aims

The expanded research questions are listed below:

1. What epigenetic changes occur in COPD?

  • In patients with a smoking history (current and former)
  • In patients without any smoking history
  • In patients without smoking history but exposed to occupational risk factors of COPD.

2. What COPD stage or symptoms are these changes associated with? 

3. What are the functional consequences of the epigenetic changes that occur in COPD?

4. How do the functional consequence of the epigenetic changes in COPD associate with defined COPD phenotypes?

5. Do these epigenetic changes predict COPD outcomes? And what are the predicted outcomes?

6. Can the reversal of epigenetic changes in COPD affect disease prognosis?

How will the research be carried out?

To answer these questions, we are developing a chronic smoking cell model of A549 and Beas2B cells.

Why is this research needed?

In 2015, COPD led to an estimate of 3.17 million deaths, equivalent to five percent of all deaths recorded that year.

The global burden of disease studies also reported a prevalence of 251 million cases of COPD globally for the year 2016 (WHO, 2017a).

The burden of COPD is much more than its mortality. An international survey of COPD’s impact in the working age population by Fletcher et al., (2011) revealed a cost of £1,500 per person per annum to the healthcare system, and an individual lifetime income loss of about £200,000 per person due to premature retirement as a result of COPD.

In the United Kingdom, the prevalence of COPD has increased by about 27% within the last 10 years (Snell et al., 2016). COPD is the fourth leading cause of global deaths. The disease is progressive and has no cure. The heterogeneous nature of the disease has also made it difficult to predict patient outcomes, identify early stages of the disease and provide proactive individualized therapy.

Previous research has shown that the epigenome is modified in response to smoking. Key differentially methylated genes such as AHRR have been used to positively predict the smoking history of patients.

From epigenome wide studies in COPD, many differentially methylated genes have also been identified as being associated with COPD phenotypes.

However, not much has been researched about epigenetic differences that may occur within COPD patients which are strong enough to identify these patients, or predict patient prognosis. 

Proposed outcomes

Research in this area is important as it will not only improve understanding of the disease, but also enable the creation of targeted therapy to improve the quality of life of patients.

Beneficiaries of this study include the academic community, pharmaceutical industry, healthcare institutions and the general public who are interested in understanding the disease.

Study findings will be made available in the BCU research repository and the electronic thesis online service (EThOS), so that information therein can be easily accessed by academic researchers.

Results generated from this study will also be published in peer review journals to be made available to researches and the general public.

The study will provide novel findings to researchers studying epigenetic modifications, COPD, and other progressive lung diseases.

The pharmaceutical industry may also benefit from this study because disease biomarkers are important in developing targeted therapies as they can be used to track the efficacy of treatment.

In the healthcare industry, cost of treatment and interventions can be reduced if patients are provided with individualised therapy, based on their epigenetic profile.

Also, the ability to predict patient’s COPD prognosis may reduce the incidence of exacerbations as patients will be proactively managed.