Considering Phenotypic Traits vs Asthma/COPD in Airway Disease Prognosis

Which better predicts risk of exacerbation in airway disease, phenotypic traits or a diagnosis of either asthma or COPD?

Although patients with asthma and chronic obstructive pulmonary disease (COPD) have a comparable risk for moderate exacerbations, the risk for severe exacerbations is greater among those with COPD than among individuals with asthma, and that risk cannot necessarily be assessed based on phenotypic traits, according to findings recently published in Respiratory Medicine.

Investigators analyzed data from the prospective Copenhagen General Population Study (CGPS), a cohort study of the general population residing in Greater Copenhagen, to test the hypothesis that individuals with asthma or COPD diagnoses had a similar risk for moderate or severe exacerbation when adjusted according to differences in phenotypic traits.

The current study enrolled 7190 individuals with chronic airway disease from CGPS: 2997 patients with asthma, 2469 with COPD, 834 with early-onset asthma-COPD overlap (ACO), and 890 with late-onset ACO. Researchers recorded participants’ phenotypic traits at baseline and assessed their risk of moderate and severe exacerbations from 2003 to 2013, according to diagnosis of asthma or COPD, with and without adjustment for phenotypic traits.

In those with asthma, clinical COPD, and ACO, a total of 7644 moderate exacerbations and 1315 severe exacerbations were recorded over 35.237 person-years of follow-up.

In a model that was only adjusted for sex, age, and education, the incidence rate ratio (IRR) of moderate exacerbations in patients with clinical COPD was 1.61 (95% CI, 1.27-2.02) relative to individuals with asthma. Following the inclusion of phenotypic traits, however, the IRR was 1.05 (95% CI, 0.82-1.35).

Notably, for severe exacerbations, the corresponding IRRs relative to asthma among participants with clinical COPD were 3.82 (95% CI, 2.75–5.35) when adjusted only for sex, age, and education and 2.28 (95% CI, 1.63–3.20) when taking into account phenotypic traits.

Among the 16 phenotypes previously associated with risk for exacerbations in patients with chronic airway disease, 13 were included in the final model. The phenotypic trait most strongly associated with exacerbations was presence of peripheral oxygen saturation less than 95%, with an IRR of 2.00 (95% CI, 1.70-2.34). The second strongest association was reported with an increase in leukocyte count (IRR, 1.10; 95% CI, 1.07-1.14). Further, higher body mass index was linked to a reduced risk for exacerbations, suggesting that being underweight was related to a higher exacerbation risk. Although most of the phenotypic traits included were associated with a higher risk for exacerbations, allergic rhinitis was linked to a lower risk (IRR, 0.71; 95% CI, 0.57-0.88). Additionally, a greater risk for exacerbations was also reported among those with high eosinophil counts.

The investigators concluded that when assessing the prognosis of patients with chronic airway disease, consideration of phenotypic traits cannot fully replace a diagnosis of asthma and COPD, given that COPD is associated with a higher risk of severe exacerbations than asthma.  

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Vedel-Krogh S, Nielsen SF, Nordestgaard BG, Lange P, Vestbo J. Asthma and COPD versus phenotypic traits: toward precision medicine in chronic airway disease. Respir Med. Published online July 7, 2021. doi:10.1016/j.rmed.2021.106529