COPD is more than a lung disease

Ruth Tal-Singer works in respiratory research and development. Here she shares her unique perspective on how the future of COPD treatment is changing, and how it's about treating more than just the lung. 

Our history in making respiratory medicines did not begin with Ventolin in 1969. Indeed, two of GSK’s legacy companies, Burroughs Wellcome Co. and Allen & Hanburys, were making inhalers for patients with lung diseases as far back as the 1880s! As I reflect on this fact, I feel very proud to see how far we’ve come in helping patients breathe better and live more productive lives.

Pocket inhaler
Selection of Allen & Hanbury inhalers, 1890s (GSK Heritage Archive)

With World COPD Day approaching this month, I think it’s important to recognise the misconception that Chronic Obstructive Pulmonary Disease (COPD) is now ‘sorted’, and that current therapies and preventive measures such as smoking cessation aides, environmental pollution control, and education activities will suffice. They absolutely won’t.

Understanding COPD better

There are approximately 384 million people suffering from COPD worldwide and many more people remain undiagnosed. The disease is normally diagnosed in midlife, commonly when someone is over 50 years old, but the disease actually starts well before they are diagnosed and treated. I believe in most cases it can and should be prevented - if we find a way to help people understand the importance of breathing clean air and if we can identify people who are at risk of developing this disease.

Despite the number of effective treatments options now available to COPD patients, many individuals continue to suffer from symptoms that impact their daily lives. The disease is defined by airflow limitation and most current therapeutic approaches are focused on addressing lung-related problems.

But there is more to treating COPD than can be measured by assessing just the lung - it is a disease that can impact the entire body: the muscles, the heart, the kidneys and the bones.

The late John Walsh who founded the COPD Foundation has been my inspiration and guiding light in working to improve the way we study and understand COPD. John was born with a genetic mutation (A1AT deficiency) that led to the development of a severe form of COPD. He was an energetic leader, relentless in the pursuit of public awareness of COPD, disease prevention and access to good healthcare and better medicines for patients.

He needed inhaled medicines to help him breathe, and he used oxygen for flights that took him across the globe to meet with patients, researchers and governments. He exercised daily, always making sure he walked 20,000 steps a day (much more than I achieve!!) and was always engaged and energetic.

Throughout my career, meeting patients like John first-hand has been so important, not only in helping me understand the disease better – but in taking their experiences back to all my research activities and motivating us to keep exploring, keep testing new candidate therapies and innovative drug development tools, like breath analysers or digital tools that patients can use at home to measure their lung function, physical activity or sleep.

In early 2005, I was involved in the design of the first large COPD disease-understanding observational study sponsored by a pharmaceutical company. At the time, industry trials were mostly focused on testing medicines or on supporting academic collaborative studies aimed at disease understanding in a few hundred or less participants. However, this one involved 2,164 COPD participants and 500 participants without COPD. The study was ground-breaking in that fact but also in that it involved close collaboration and data sharing across the industry – something someone had once told me was an impossibility – like turning the sunken Titanic!

The study was called Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, or as most people call it, ECLIPSE. GSK took part in this study because we recognised that if we really wanted to make an impact, we had to take a more active role in discovering what matters most to patients and improve the way we conducted clinical trials that tested new medicine candidates.

Treating more than the lung

In data from ECLIPSE we recently described a group of participants with Multi-Organ Loss of Tissue or ‘MOLT’. These patients demonstrated accelerated worsening of emphysema (over inflation of the air sacs in the lung) but they also reported more bone loss (osteoporosis) and demonstrated more body and muscle mass loss over the three-year duration of the study. We also observed there were more deaths and events requiring hospitalisation in these patients.

The study revealed participants in the MOLT group had a specific pattern of protein biomarkers (a molecular fingerprint) in their blood, which suggested these patients have a defect in their body’s ability to repair tissue. So, although current therapies can help them with their symptoms, we must still find a way to prevent their progressive decline. 

Scientist working with plates and pipette
Working with plates and pipette in the respiratory SMART lab - Stevenage, UK

We also reported about a group of individuals in ECLIPSE who had a different and persistent pattern of inflammation biomarkers in their blood - this group had high incidence of cardiovascular disease, high blood pressure (hypertension) and diabetes. Cardiovascular disease is a key cause of mortality around a lung-related worsening event called COPD exacerbation.

As a scientist it is encouraging to have and share these insights in publications, but what matters most is to take this knowledge to the next step and find a way for clinicians to find these patients as early as possible and to help them stay healthy.

Several more studies have now been undertaken to understand this extrapulmonary (beyond the lungs) aspect of COPD and have given us great insight, enabling us to move forward with our research. For example, we’re now able to identify several important biomarkers that can be used in trials when we’re assessing medicines targeting the cardiovascular and muscle aspects of COPD.

Recently, in an experimental medicine study, we were also able to test a novel approach to treating vascular (blood vessel) disease in COPD for the first time in humans. After years of working in this field, this was such an exciting step for me!

The future is personal!

Now we really understand that COPD treatment cannot be one size fits all - it's not, "You have COPD, you take medicine X."

To effectively treat someone with COPD, we must understand what the markers of their disease processes are. What does the patient really need? Do they need an inhaled medicine? A bronchodilator? An anti-inflammatory treatment? Do they need a new approach to help them repair damaged tissues? Do they need a vaccine? So many questions!

To answer these questions and ensure the right medicine is given to the right patient at the right time, we are putting the information and data that has been gleaned from the many, many years of research by GSK and our collaborators to work every day in our labs. We’re incredibly hopeful that the medicines and drug candidates we have in development will come to fruition and although some of our attempts have failed and it has been disappointing, we learn from each study and strive to apply the lessons in our next attempt. 

I am incredibly proud to have been involved in programmes that later became medicines for patients and with my team I continue to push myself in every aspect of our work, from supporting early discovery in our labs, through to the development of medicines because I know the more we understand about this disease, the better we can treat it, and truly help patients to live every breath and enjoy their lives.

As John Walsh told me in 2009, working for patients is a commitment of a lifetime and I am totally in!

Find out more

See how Ruth is pushing the boundaries of emerging technologies and combining this with deeper insights into respiratory disease to deliver pioneering new solutions to patients. 

Marzo, scientist, R & D looking into microscope

This blog is part of our A view from the lab… series, sharing insights from scientists around our company. It was originally published on Ruth's LinkedIn profile.

View the series