Asthma/Obstructive Pulmonary Disease Overlap

Update on Definition, Biomarkers, and Therapeutics

August Generoso; John Oppenheimer


Curr Opin Allergy Clin Immunol. 2020;20(1):43-47. 

In This Article

Potential Biomarkers

Two biomarkers that may be of utility in identifying ACO are serum periostin and YKL-40 (Table 1). Periostin is a matricellular protein highly expressed in allergic diseases.[21,22] YKL-40 is a glycoprotein that is secreted by inflammatory and airway epithelial cells, and is upregulated in COPD.[21,22] In a study of Japanese patients with asthma (n = 177), ACO (n = 115), and COPD (n = 61), Shirai et al.[22] found that serum periostin is high in both asthma and ACO, but not in COPD. Meanwhile, YKL-40 is high in both COPD and ACO, but not in asthma. Moreover, the proportion of patients with both high serum periostin and YKL-40 levels is significantly greater in ACO than in asthma or COPD. These findings suggest that ACO has both hallmarks of asthma (T2 high inflammation) as well as COPD (neutrophilic inflammation), and thus a combined assessment using these two biomarkers may help in the diagnosis of ACO.

However, as discussed by Izuhara and Barnes[21] serum periostin and YKL-40 are not always upregulated in asthma or COPD. As such, periostin and YKL-40 are not biomarkers of asthma and COPD, but rather biomarkers of subtypes of asthma and COPD. Furthermore, they point out that Shirai et al.'s[22] findings ultimately suggest that combined assessment of these two biomarkers alone is not sufficient to diagnose ACO accurately.

Regarding another possible biomarker, Iwamoto et al.[23] found that sputum levels of neutrophil gelatinase-associated lipocalin (neutrophil-derived inflammatory molecule) was significantly elevated in ACO compared to both asthma and COPD, suggesting potential utility in distinguishing ACO as a distinct entity.

Ultimately, further studies are needed to clarify the utility of combined assessment of serum periostin and YKL-40 in ACO, as well as to look for other potential biomarkers like sputum neutrophil gelatinase-associated lipocalin.