COPD expert and GOLD Committee member Professor Alvar Agusti challenges some existing dogmas in COPD and tells conference delegates how we’re making steps towards personalized medicine.

FEV_¹ is not enough

Before 2011 COPD was easy because it was just about FEV₁, Agusti told a packed room of delegates attending the A. Menarini breakfast session Beyond COPD phenotypes – what is next.

“Everything was FEV₁ — it was what I call sequential thinking – if your FEV₁ is this, your treatment is this. The problem is that it was easy but wrong,” said Agusti who is a Director at the Thorax Institute at the Hospital Clinic in the University of Barcelona in Spain.

FEV₁ was (and is) clearly needed for the diagnosis of COPD but it was not enough to capture the complexity of the disease, hence, to guide its treatment, he said.

“There is no way that only the FEV₁ can tell you whether an individual patient has more or less symptoms, more or less exercise capacity,” he told delegates.

“It is not enough to have FEV₁, you have to think about several domains of the disease at the same time, including FEV₁, which is parallel thinking, he said.

A complex and heterogeneous disease

COPD is often talked about as being a complex and heterogeneous disease but people generally had different ideas of what the terms meant.

Complex means that COPD includes several elements that are not linearly related whereas heterogeneous means that not all of these elements are present in all patients or in a given patient at all time points, he explains.

There will be groups of patients with similar characteristics that can be grouped into phenotypes.

In a paper published in Thorax last year he describes a phenotype as something “composed of traits or characteristics, some of which are controlled entirely by the individual’s genes whereas others are controlled by genes but are significantly affected by environmental factors.”

However while phenotypes are important for research they are not appropriate for clinical practice, he says.

“How can you use the concept of phenotype if they can co-occur in the same patient?” he asks.

Identifying treatable characteristics

Instead we should identify a number of clinically relevant characteristics that are treatable.

“And then see in your patient which ones are present and what you can do to treat them,” he said.

The 2011 GOLD proposal already describes three treatable characteristics — FEV₁, symptoms, and exacerbations — and gives advice on drugs to use in these different groups.

“No question, this in my mind is a HUGE change. A very important step forward towards personalized COPD medicine,” he said.

“However, change is a process and not an event and while 2011 was an important event I think there is going to be a chain of changes that are still to come.”

Other treatable characteristics could include inflammation, prevention of lung cancer, variability in the lung microbiome, and biological disease activity, he said.

So how can we use this in clinical practice?

 Many physicians already say that the GOLD 2011 classification is already complex and wonder how they would cope if more dimensions were added.

But Agusti says that his proposal is that we develop and validate a COPD control panel, just like pilots have information on many variables they need to fly the plane safely.

While it is a concept that hasn’t been validated there may be a number of variables that can inform clinicians on the severity of the disease, he says.

For instance FEV₁, hyperinflation, respiratory failure and exercise are all severity variables that are treatable.

If a patients P02 was low you could use oxygen, if the ICTLC ratio was low you can use bronchodilators to deflate the lung.

Not all patients perceive their symptoms equally so a patient impact module could also be of interest.

And in the future you will also be able to use all the ‘omics’ to personalize treatment, he said.

It may seem overwhelming but if you buy into the concept you can customize the control panel to the place you work, says Agusti.

For example if you work in a remote area with not much access to technology you can simplify the control panel. If you work in a university or teaching hospital you might be able to have a more sophisticated one.

Challenging COPD dogma

In a challenge to existing COPD dogma Agusti also said that the role of FEV₁ to guide treatment in COPD needs to be reconsidered .

There is no question that it is essential for the diagnosis of the disease, he says.

But the problem with FEV₁ is that it is poorly related to things that matter to patients such as symptoms or exacerbations.

Do you really use FEV₁ to prescribe treatment or do you talk to your patient? Agusti asks the audience.

In an article a few months ago published in The Lancet Respiratory Medicine, he and a colleague (Dr. Leo Fabbri) officially broke this COPD dogma by calling for an FEV₁ free approach to COPD.

Their approach is similar to GOLD but there are some important differences, he explains.

“First there is no FEV₁, although you still assess the level of symptoms of the patient, and by symptoms we really mean breathlessness, and the risk of future exacerbations.”

Another important difference was that there are no magic numbers (thresholds).

“You have to assess your patients, you have to practice medicine you have to talk to your patient,” he says.

According to the proposal if a patient does not have too much dyspnea you can use a LABA or a LAMA.

“By the way, no short acting bronchodilators here as we are treating a chronic condition,” he told delegates.

If your patient had a lot of dyspnea then you use LABA/LAMA combined and wait and see if there are exacerbations.

If you can control exacerbations with this treatment then you don’t need to add anything else.

“But if you cannot and you have exacerbations you can add an ICS, either to the LABA/ LAMA or to combination which means triple therapy. And if you fail that means you can consider other treatment.”