Phenotypic characterisation of early COPD: a prospective case-control study

Abstract

The phenotypic characteristics of chronic obstructive pulmonary disease (COPD) in individuals younger than 50 years of age (early COPD) are not well defined. This prospective, multicentre, case-control study sought to describe these characteristics and compare them with those of smokers (≥10 pack-years) of similar age with normal spirometry (controls). We studied 92 cases (post-bronchodilator forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) <0.7) and 197 controls. Results were contrasted with participants with similar inclusion criteria recruited into the ECLIPSE and COPDGene cohorts. Cases had moderate airflow limitation (FEV₁ 71.3±20.8%) but were often symptomatic, used healthcare resources frequently, had air trapping (residual volume 150.6±55.5% ref.), had reduced diffusing capacity (84.2±20.7% ref.) and had frequent evidence of computed tomography (CT) emphysema (61%). Of note, less than half of cases (46%) had been previously diagnosed with COPD. Interestingly, they also often reported a family history of respiratory diseases and had been hospitalised because of respiratory problems before the age of 5 years more frequently than controls (12% versus 3%, p=0.009). By and large, these observations were reproduced when available in the ECLIPSE and COPDGene cohorts. These results show that early COPD is associated with substantial health impact and significant structural and functional abnormalities, albeit it is often not diagnosed (hence, treated). The fact that a sizeable proportion of patients with early COPD report a family history of respiratory diseases and/or early-life events (including hospitalisations before the age of 5 years) renders further support to the possibility of early-life origin of COPD.

FIGURE 1

Frequency distribution of age (years), cumulative smoking exposure (pack-years), FEV₁/FVC (%), FEV₁ (% ref.), diffusing capacity of the lung for carbon monoxide (D_LCO) (% ref.) and KLCO (% ref.) in patients (red; n=92) and controls (green; n=197). Dotted vertical lines represent mean values. For further explanations, see text.

FIGURE 2

Comparison of the main characteristics determined in patients with early COPD (versus controls) in the three cohorts studied here (our own (SPAIN), ECLIPSE and COPDGene). ↓ Indicates reduced in cases, ↑ indicates increased in cases, ∼ indicates similar in patients and controls, and NA means not available in that cohort. Orange, pink and yellow rows indicate, respectively, reproducibility of findings in three out of the three cohorts, two out of two cohorts or two out of three cohorts where this information was available. For further explanations, see text.

FIGURE 3

Variables associated (p<0.05) with the presence of early COPD in the population studied. Node colour indicates variable category (see legends), node size is proportional to the prevalence of abnormal values of that particular variable and edge (link) width is proportional to p-values (see legends). For further explanations, see text.