The overlap phenotype: the (missing) link between asthma and COPD

Abstract

The definition of chronic obstructive pulmonary dis-ease (COPD) as a preventable and treatable conditioncharacterized by a not completely reversible chronicairflow obstruction [1] is so broad and imprecise thatmany different types of patients with distinct clinicalcharacteristics, prognosis and response to treatmentsmay fit in. These different types are now described as“clinical phenotypes” and the interest in their defin-ition and characterisation is growing [2]. Among thesephenotypes, the so-called overlap of syndromes withairflow obstruction is usually poorly considered [3].In a first step of phenotyping, a COPD patient canpotentially be classified as a predominant parenchymaldestructive or predominant airflow limitation phenotypeby using a few clinical, radiological and functional findings[4]. However, when a patient presents characteristics andsymptoms of two or more respiratory diseases at the sametime, this is described as an overlap syndrome. In particu-lar, the asthma-COPD overlap phenotype has beendescribed as symptoms of increased variability of airflowin association with an incompletely reversible airflowobstruction [5]. From a clinical point of view it usuallycorresponds to individuals diagnosed with asthma beforethe age of 40 who, at an older age, fulfil the criteria forCOPD [6]. Recent estimations of its prevalence report thatabout 13-20% of subjects with COPD have the overlapphenotype [6,7], with an increasing trend in the elderlypopulation (up to 50% in those aged over 70 years) [7].Since they have been systematically excluded from bothCOPD and asthma pharmacological clinical trials as notbeing “pure” subjects, it is clear that we cannot really knowthe response to pharmacological treatment of a significantnumber of patients with COPD.Increased reversibility is one of the key differentialaspects of individuals with the overlap asthma-COPDphenotype. Reversibility in COPD is not only possiblebut it is also not so infrequent: indeed, significant re-versibility in COPD is observed frequently in everydayclinical practice and in a series of patients included in thenewly designed clinical trials [8]. Over one half to almosttwo-thirds of the patients with moderate-to-very-severeCOPD participating in the large clinical trial UPLIFT metthe most commonly used criteria for acute bronchodilatorresponsiveness [9]. In a recent study of COPD patientswithout a prior history of asthma, 44% of the subjectsshowed a positive bronchodilator test with an inverse cor-relation between bronchodilator reversibility and theGOLD severity stages [10].Reversibility, however, has not been considered to be areliable parameter to diagnose or classify patients; thereason being that a patient may be reversible or irrevers-ible in different determinations at different time points[11]. This is a consequence of dichotomising a continu-ous variable as positive or negative. In fact, this approachcould be valid for epidemiologic studies but should neverbe used to guide clinical decisions in an individualpatient. Reversibility in clinical practice must be consid-ered as a continuous variable, and therapeutic decisionsshould be made according to the magnitude of thechange. One example will help to explain this concept: apatient with a reversibility of 11.8% in forced expiratoryvolume in the 1