Clinical characterization of COPD is unfolding fast. Concepts evolve from a disease manifested by fixed airflow obstruction with distinguishing between “pink puffers” and “blue bloaters” to the ongoing paradigm of COPD as a wide range of clinical phenotypes.
Defining Clinical Phenotypes in COPD
Clinical COPD phenotypes are a single or combination of disease attributes that describe distinctions between patients with COPD as they correlate to clinical meaningful results. These include symptoms, exacerbations, response to therapy, rate of disease progression, or death.
In a broader context, Feinstein characterized the two purposes of defining a clinical phenotype. And they are giving a certain name to a disease or condition – to identify a certain natural history or prognosis and to define a specific therapy.
While a multitude of supporting features can distinguish among patients with COPD, clinicians will particularly value distinguishing between COPD phenotypes to the extent that the patient’s management is influenced by identifying their phenotype.
The parameters on which the current spectrum of COPD phenotypes have been defined are the following:
- Lung function in early adulthood and also the rate of progression
- Symptom profile such as the presence of chronic bronchitis or linked asthma
- Degree of physiologic derangement, for example, degree of FEV1 impairment
- Radiographic features including airway thickening vs. emphysema, concomitant pulmonary fibrosis or bronchiectasis
- Natural history
- Associated biomarkers
- Genetic risk factors
Some of the currently described COPD phenotypes are:
- Alpha-1 antitrypsin deficiency
- Frequent exacerbator
- Chronic bronchitis
- Combined asthma-COPD
- Combined pulmonary fibrosis-emphysema
Identifying Increased Risk for COPD
Lange and colleagues in the New England Journal of Medicine did a study that highlights the utility of phenotyping in identifying populations at risk for developing COPD.
They utilized three large longitudinal cohort studies. The participants underwent serial spirometry over greater than 20 years, beginning before age 40.
The serial measurements allowed the calculation of the rate of decline in lung function and a determination of whether COPD ultimately developed based on GOLD diagnostic criteria.
Confirming observations ensued from previous studies, patients with a normal FEV1 before the age of 40, who eventually experienced an accelerated decline in lung function, defined one phenotype at an increased risk of developing COPD.
A second phenotype which hasn’t been previously identified was manifested by individuals with a low FEV1 in early adulthood and a relatively normal rate of decline in lung function.
Linking Phenotypes to Therapy
The most immediate and present impact of characterizing different COPD phenotypes is identifying specific therapy that is linked to the phenotype. This is of special interest to clinicians.
Let’s take a look at the example of alpha-1 antitrypsin deficiency (AATD). Identifying individuals with this particular genetic condition that predisposes to COPD has three potential managerial impacts:
- Since AATD is inherited as an autosomal co-dominant manner, first degree relatives are at risk for having a severe deficiency of alpha-1 antitrypsin (AAT) and they are ought to be tested for AATD.
- Because smoking cigarettes especially accelerates progression of emphysema in AATD, avoiding smoking or smoking cessation must be extraordinarily emphasized for affected individuals.
- Seeing that specific therapy exists, the clinician may consider recommending intravenous augmentation therapy with pooled human plasma-derived AAT.
Also, consider the value of identifying individuals with chronic bronchitis and moderately severe airflow obstruction. The efficacy of the phosphodiesterase-4 inhibitor, roflumilast, to avert exacerbations has been analyzed and demonstrated in this specific subset of COPD patients.
All in all, the current thrust to identify specific and distinctive clinical phenotypes in COPD will surely go on. Beyond the value of this line of inquiry in helping to identify specific pathogenetic mechanisms and prognosis in COPD, clinicians will particularly value identifying phenotypes that link to specific therapies.