5 Exacerbation-prone Phenotypes Were Discovered Among Asthma and COPD Patients

Five phenotype clusters were discovered to be associated with the exacerbation, or worsening, of chronic inflammatory airway diseases of asthma and chronic obstructive pulmonary disease (COPD), which are syndromes with diverse clinical systems. According to a PLOS ONE study published in late-March 2022, the five identified clusters go beyond disease labels.

While asthma and COPD share common characteristics of an increased decline in lung function, poor quality of life and increased mortality, the mainstream approach to treating these inflammatory diseases has been to name a diagnosis first, then to follow the clinical guidelines that correspond to that diagnosis. However, that approach has been reported to have limitations in providing appropriate treatment.

On the other hand, there is a new proposed concept researchers of the study are calling treatable traits. This new concept evaluates treatment options based on the clinical characteristics and features of individual patients without being distracted by diagnostic labels.

To get a better understanding of each chronic inflammatory disease and how to treat them, researchers of the study were looking to clarify the exacerbation-prone phenotypes beyond disease labels of patients with asthma, COPD and asthma-COPD overlap syndrome. Researchers used their common and shared risk factors to do so and to investigate the role of the IL4RA gene polymorphism rs8832, which is related to type 2 inflammation in these exacerbation-prone phenotypes.

Researchers conducted cluster analyses from January 2017 to December 2017 using patients of the University of Tsukuba Hospital in Tsukuba, Japan or affiliated locations with at least one exacerbation within the previous year. There were 117 patients with asthma examined, 37 with ACO and 48 with COPD.

According to the study, exacerbation is defined as the need for intravenous infusion of steroids, either an increased dose or at least 3 days of oral administration of steroids, or antibiotic use due to worsening symptoms within the previous year.

Looking into the role of the IL4RA gene, a control group of 1,529 adults without asthma or COPD were included in multinomial logistic analyses. The genetic influence of rs8832 was also evaluated in 130 patients with asthma with allergic rhinitis but without history of exacerbation.

The data resulted in these five clusters that were “good cluster quality”:

• Cluster 1: patients with high eosinophil counts.
• Cluster 2: smokers with impaired lung function.
• Cluster 3: patients with Gastroesophageal reflux disease or acid reflux.
• Cluster 4: non-allergic females.
• Cluster 5: patients with allergic rhinitis and high levels of Immunoglobulin E

Data shows exacerbations treated by steroids were most frequent in cluster 5, while exacerbations treated by antibiotics only were most frequent in clusters 2 and 3. Clusters 1 and 3 were inconsistent with disease labels for asthma and COPD. In addition, cluster 1 was deemed an exacerbation-prone phenotype, particularly associated with eosinophilic airway inflammation.

There was also a significant association found between cluster 5 and rs8832, as well as between type 2 exacerbation-prone phenotypes and rs8832 for clusters 1 and 5.

While genotyping for rs8832 was unsuccessful in some patients in the cluster analysis, multinomial logistic regression analyses of the G allele of rs8832 showed it was significantly associated with the cluster 5 group. A similar trend was also observed with cluster 1.

Results indicated the clinical heterogeneity of disease exacerbation may reflect the presence of common exacerbation-prone endotypes across asthma and COPD. These clinical differences may also support the use of the treatable traits approach for the treatment of exacerbations of chronic inflammatory airway diseases, according to the study.