Confronting COPD in the Era of Personalized Medicine
By: Nicola A. Hanania, MD, MS, FCCP
November 17, 2021
Chronic obstructive pulmonary disease (COPD) is a serious and debilitating lung disease. COPD impacts an estimated 280 million people worldwide. It is the fourth leading cause of death and the third most common cause of disability in the US, where the projected annual cost of patient-related care in 2020 was $49 billion. In the US, 16 million people have COPD, and each year, more than 150,000 people die because of it. The numbers tell only part of the story, however.
For many who live with the disease, getting through each day is often a struggle. Over the years, COPD has shifted from being a disease of “old men” to a disease that is more common in women and in patients who smoke and who are 40 years of age or older. While cigarette smoking is the leading cause of COPD, 1 out of 4 people with COPD have never smoked. In addition to genetic predisposition, other risk factors that have been identified as risk factors of progression of the disease include poor lung growth and recurrent respiratory infections during childhood as well as exposure to pollutants and secondhand smoke. Every November, the COPD community comes together to raise awareness about COPD and its symptoms in an attempt to improve its early diagnosis, management, and ultimately, its outcomes.
The Challenges
While COPD is an old disease, health care workers often face challenges dealing with this impactful disease. While many patients have been diagnosed with COPD, millions more are believed to have it and not know it. This delay in diagnosis may be due to patient factors and health care provider factors. Because COPD symptoms develop slowly and worsen over time, many patients who have the disease delay getting diagnosed until they need aggressive treatment or hospitalization. At the same time, health care providers often do not have COPD on their radar when they see patients in their clinic who are older than 40. Many fail to ask about specific symptoms such as “smoker’s cough,” decrease in activity, or fatigue, which may be early signs of the disease. Furthermore, many do not use spirometry, which is an essential tool for diagnosis and staging the disease.
For many years, many health care providers believed that there is nothing they can offer patients with COPD, and these nihilistic thoughts may have contributed to delay in the diagnosis of the disease. Another challenge for health care providers is the fact that COPD has multiple phenotypes and is not a “one size fits all” disease. Indeed, COPD has multiple faces, which may be reflected upon by its clinical presentation—radiologic findings as well as airway inflammatory profile. Such phenotypes may explain the differences in response to therapy among patients with the disease. In the era of personalized medicine, the use of physiologic, biologic, or radiologic biomarkers may lead to improvement in the precision approach to this old disease. In addition, COPD is often associated with one or more comorbidities which may complicate its course and which need to be identified and treated. Finally, assessment of COPD should include assessing symptoms and risk of exacerbations in addition to lung function. Grading COPD according to symptoms and exacerbation risk is essential to initiate the appropriate pharmacologic therapy.
The Opportunities
While there is no cure for COPD, it is a treatable disease, and there are many avenues that health care providers can offer their patients to improve their symptoms, lung function, quality of life, and exercise tolerance and to reduce exacerbations and hospital admissions. In addition, there are a few avenues that may reduce mortality from this disease. These interventions can be nonpharmacologic and pharmacologic. Smoking cessation is the most important intervention, but other nonpharmacologic interventions include promoting daily activity and exercise, formal pulmonary rehabilitation, as well as preventing the exposure to secondhand smoke, irritants, and infection. For those living with COPD, vaccinations against influenza, pneumococcal pneumonia, and COVID-19 are of paramount importance. Oxygen therapy has been shown to reduce mortality in hypoxemic patients. Surgical lung volume reduction should be restricted to those with upper lobe emphysema with poor exercise tolerance. In recent years, bronchoscopic lung volume reduction using valves has taken over the need for surgery in many of these patients with emphysema.
Multiple medications are now available to treat COPD and have been shown to reduce exacerbations. The approach to choosing medications should be driven by the grade of the disease and the occasional use of biomarkers such as blood eosinophil count, which is a good predictor of exacerbations as well as response to inhaled corticosteroids. The use of dual bronchodilator therapy (LAMA/LABA) has been shown to be superior to monotherapy in improving symptoms and reducing exacerbations. In addition, the use of triple therapy (ICS/LABA/LAMA) has recently been shown to reduce mortality in two large studies in high-risk patients. Two such triple therapies have now been approved in the US for COPD.
Multiple targeted biologic therapies are being tested in patients with severe COPD at risk of exacerbations. Identifying the predictors of response to such agents has been the most challenging and will need to be properly investigated in future studies.
In summary, despite all the above challenges, there seems to be a light at the end of the tunnel dealing with this old disease. It is imperative, however, that one continues to think differently about this disease and be prepared to use more appropriate phenotyping and endotyping (in the future) to improve the personalized approach to its treatment.
Nicola A. Hanania, MD, MS, FCCP
Dr. Hanania is the Director, Airways Clinical Research Center, at Baylor College of Medicine in Houston, TX. He is a member of the CHEST Education Committee and the CHEST Journal Editorial Board.