Asthma-COPD Overlap: Diagnosing and Managing This Critical, Yet Understudied Disease

Navitha Ramesh, MD


October 08, 2018

Editorial Collaboration

Medscape &

Hello. My name is Navitha Ramesh. I am a clinical assistant professor of medicine at Geisinger Commonwealth School of Medicine in Scranton, Pennsylvania.

Today I'm here to talk about asthma–chronic obstructive pulmonary disease overlap (ACO) as part of the collaboration between CHEST and Medscape.

Understanding ACO and Its Impact

ACO is a hot topic these days, but what exactly is it?

This disease is not well defined. In 2015, the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a combined statement describing this disease,[1] which noted that ACO is seen in patients who have clinical features of asthma as well as clinical features of chronic pulmonary obstructive disorder (COPD).

This disease dates back to the 1960s when something was put forward called the Dutch hypothesis,[2] which states that airway hyperresponsiveness and atopy are markers of intrinsic predisposition to chronic airways disease in the future. Asthmatics who have had asthma since childhood and who have risk factors such as smoking or biomass fuel exposure tend to develop COPD-like features in their later years of life. This is a phenotype of patients who could have ACO.

Worldwide, asthma affects an estimated 300 million people and COPD [an estimated 210 million],[3,4] so it's only natural for some patients to have a combination of both diseases. This category of patients constitutes the ACO group.

You may ask why it is important to even acknowledge ACO. First, there are not many studies looking specifically at this population. The information we have so far is extrapolated from data obtained from asthma and COPD studies where the patients with this overlap have been excluded.

Twenty years ago, a study was published in the New England Journal of Medicine which looked at asthmatic smokers.[5] It showed that asthmatics who smoked had a greater decline in their lung function when compared with asthmatics who did not smoke and also in smoking non-asthmatics.

In the recent ECLIPSE study,[6] a comparison was made with COPD patients with and without ACO symptoms. It showed that the ACO population predominantly comprises a younger patient group, mostly women. They had significant decrease in their lung function, more exacerbations and hospitalizations, and increased symptomatology of wheezing and breathlessness.

Based on this, we now know that patients with ACO have lower lung function, more severe disease, more severe exacerbations, increased healthcare utilization and hospitalizations, as well as increased mortality. That is why this disease entity is important.

Putting ACO Into Practice

Which groups of patients in your clinical practice should you suspect of having ACO? The first is those who have been asthmatic since childhood and have developed fixed airway obstruction as a result of smoking or having any other noxious stimuli exposure. The second is patients with COPD who have significant atopic or T-helper type-2 (Th2) features. The third is patients with COPD or a clear risk factor for COPD like smoking, in addition to bronchial hyperresponsiveness, defined as post-bronchodilator FEV1 increases > 400 mL.

Based on this, you can see that this is not a specific disease. There are various phenotypes within ACO, a disease entity for which we do not have much data.

We know that this exists, so how do we diagnose and manage it? The latest guidelines from GINA and GOLD[1] recommend a stepwise process.

The first step here is confirming that the patient has a chronic airways disease. This is made from a patient history and physical examination.

The second step would be spirometry with bronchodilator testing. About 80% of patients with ACO can be diagnosed with the first two steps, a thorough history and spirometry with bronchodilator testing. The remaining 20% or so need additional testing, which includes serum immunoglobulin E levels, blood and sputum eosinophil levels, and exhaled nitric oxide, just to name a few.

The next step would be to categorize these patients into three groups according to syndromic diagnosis. Do they have lone asthma? Do they have lone COPD? Could they have ACO?

Management Strategies

The next step is the management of the disease itself.

Number one is to advise your asthmatic patients not to smoke, and if they are smoking, then to quit. That is the key. The second is identifying and avoiding triggers for the asthma. The third is identifying comorbidities, which are very well described in both the asthma and COPD populations. Identifying and managing these comorbidities is key. If patients have significant allergic rhinitis, they could use intranasal steroids and montelukast.

Inhaler therapy is central to the management of ACO. Inhaled corticosteroids are the backbone for treatment of asthma, as we all know. However, for COPD, inhaled corticosteroids have been shown to increase the risk for pneumonia. Hence, based on the GOLD guidelines,[7] inhaled corticosteroids are recommended in groups with significant exacerbations. We definitely have to classify these patients and say if they have ACO for sure. If we strongly think that they could have the disease entity, based on history and spirometry, then it is best to start them initially on an inhaled corticosteroid. A long-acting beta-agonist and a long-acting muscarinic antagonist can be used as add-on therapies to the inhaled corticosteroids.

Several recent studies have looked into biologic medications in the management of both asthma and COPD. A 2017 study published in CHEST showed that anti-IgE therapy with omalizumab improved the asthma control and health-related quality of life in severe asthma patients with overlapping COPD.[8]

Anti–IL-5 therapies have been shown to be very beneficial in severe eosinophilic asthma. What is the role of these medications in ACO? The two main studies looking into the anti–IL-5 mepolizumab for severe eosinophilic asthma are MENSA and DREAM. The post-hoc analysis of these trials showed that mepolizumab was associated with lower exacerbation rates in patients with severe asthma and in those who had overlapping features of COPD.[9,10,11] Another study, published in the New England Journal of Medicine,[12] looked at the utility of mepolizumab in the treatment of COPD patients, who were already receiving maximum inhaled therapy for COPD, including inhaled corticosteroids, long-acting beta-agonists, and long-acting muscarinic antagonists. Mepolizumab did show a deceased exacerbation rate in patients with COPD who did have features of atopy or asthma.

Implications for the Future

Based on what we know so far, this is a specific subset of the population who has ACO. Sometimes it is hard to believe that you could have two airway disease processes in a single patient, but this can happen, and this disease is evidence for that.

What are the implications for the future for ACO?

Number one is to have a better definition of the disease. Number two would be to look at this specific disease phenotype and to understand the disease process so that therapies can be targeted based on the pathologic mechanisms.

Down the line, this disease could get a new name. Maybe it is going to be called Th2 COPD or eosinophilic COPD, so we will just have to wait and watch. At this time, we need more studies, and we need more literature in this specific patient population.

This is Dr Navitha Ramesh on behalf of the collaboration between CHEST and Medscape. Thank you for listening.


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