It was Renne H. Laennec who close to 200 years ago first described the anatomic and clinical expression of a lung disease that he named emphysema, from the Greek “puff up” or “inflation.”1 Over the following 150 years, debates were held over the nomenclature of that chronic disease associated with bronchitis and frequently with anatomical emphysema. Finally, in the 1950s, the term chronic obstructive pulmonary disease (COPD) was introduced to encompass both bronchitis and emphysema, as they shared the presence of airflow limitation during the performance of a forced vital capacity maneuver.2 With minimal changes, the definition of COPD had remained stable over the years with the assumption that its primary causative factor, at least in developed countries, was chronic exposure to cigarette smoke.3 Thus, for most of the 20th century, COPD was thought to be a self-inflicted disease of elderly smokers, with the only therapy that could really alter its relentless progression being smoking cessation. Fortunately, research conducted over the last 3 decades has significantly challenged these long-held beliefs. First, population and cohort studies around the world have shown that COPD has causes other than cigarette smoking, and that there are different trajectories of lung function from birth to adulthood.4 Second, in many persons (the “low flyers”5), events affecting early lung development may lead to airflow limitation starting from the first years of life or even birth. Thirdly, the combination of advanced imaging techniques, particularly computerized tomography of the chest, and high throughput “omics”, has greatly enhanced basic biological studies aimed at dissecting the diverse pathobiological mechanisms, or endotypes, and clinical phenotypes of COPD. Finally, increased computer power has provided the capacity to use “big data” to integrate complex observations, thus providing a better picture of the interaction of the biological processes occurring in the transition from health to disease.

To reflect these evolving concepts, an updated COPD definition, nomenclature and taxonomy have been proposed, focused on the different causes of COPD, the structural and physiological pulmonary abnormalities that may precede full-blown clinical disease, and the heterogeneous symptoms and biological changes that can occur at any age.6 We now know that the two major players of the former COPD definition, the absolute need for spirometric obstruction and exposure to cigarette smoke, are losing center stage to make space for a more patient-fitting definition aimed at earlier detection of the disease, precise definition of the different pathobiological pathways, and the implementation of novel therapies.

Despite these advances, COPD is still underdiagnosed, underfunded, and understudied. As a result, pharmacological therapies for COPD are currently limited. Years of randomized clinical trials, centered in older smokers with significant disease, have shown some success in improving lung function, symptoms, decreasing exacerbations and risk of death, but remain well short of the success seen in the treatment of other chronic conditions such as cardiovascular, neurological and oncological diseases. This is in part due to the fact that the recruitment of COPD patients for clinical studies has been primarily guided by COPD severity as measured by airflow limitation. However, due to the advances in our understanding of COPD, the time has arrived to conduct studies tailored to the pathobiological and clinical features of the patients to be treated (Fig. 1). In this editorial, we review some potential COPD subtypes that can be targeted with current and novel therapies, aimed at altering disease progression while simultaneously exploring their biological pathways so that more precise medications can be developed in the future.

Fig. 1.

COPD subtypes, biomarkers, and pharmacotherapy.

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Although our understanding of the cellular and molecular mechanisms underlying COPD has improved in recent years, the persistent lack of understanding of the different COPD subtypes explains why there is no therapeutic intervention that significantly halts the disease progression (Fig. 1). Many clinical trials with negative results have led to the exclusion of potentially beneficial drugs for the treatment of COPD when the real problem was the identification of the appropriate patient population that could benefit from such therapy.22 Thus, a shift is urgently needed to identify biomarkers and start tailoring the therapies according to the pathobiological processes underlying the different COPD subtypes. The proposed change in COPD definition, its nomenclature, and taxonomy offers an anchoring ground to target specific COPD subtypes and to use this paradigm shift for the help of COPD patients.

FP and BC equally contributed to the writing of the manuscript.

This study has been funded by the NHLBIR01 HL149744 and the Baylor College of Medicine discretionary funds to Dr. Polverino.

FP has received funds from Boehringer Ingelheim and is section editor of the European Respiratory Journal.