Chronic Rhinosinusitis With Nasal Polyps Linked to Distinct Asthma Subphenotypes

Researchers have identified distinct clusters of asthma associated with chronic rhinosinusitis with nasal polyps (CRSwNP), which supports disease heterogeneity and suggests different underlying mechanisms for asthma. These were among study findings published in Clinical & Experimental Allergy.

In patients with asthma and concomitant CRSwNP, the asthma is usually more difficult to control and inflammatory. To better individualize treatments for this population, investigators conducted a clinical trial (ClinicalTrials.gov: NCT03694847) to identify and characterize subphenotypes of asthma in patients with asthma and concomitant CRSwNP, based on clinical, physiological and inflammatory variables.

Data were obtained from the Quebec Heart and Lung Institute-Laval University asthma databank. Study participants were adults with a confirmed diagnosis of asthma who had stable asthma and had used asthma medication for at least 4 weeks before data analysis. In participants with CRSwNP, the diagnosis had been confirmed by an otorhinolaryngologist. A total of 1263 participants were included — 178 (14.1%) had asthma with CRSwNP (median age, 50.8 years; 52% male), and 1085 (85.9%) had asthma without CRSwNP (median age, 38.6 years; 38% male).

K-means cluster analysis was conducted using 17 clinical, physiologic, and inflammatory variables, which were selected based on their contribution to the characterization of asthma and/or asthma with the CRSwNP phenotype. Analysis of the overall population identified 3 distinct patient clusters. Cluster T1 was the largest group (n=708) and included the youngest participants (median age, 29.4 [28.6-30.1] years) and those with the highest prevalence of atopy (93.7%), the mildest asthma (n=471), and the lowest prevalence of CRSwNP (4.9%).

The other participants were almost equally grouped in clusters T2 (n=263) and T3 (n=292). Cluster T2 included participants with the longest mean (SD) asthma duration (35.2 [33.8-36.5] years), and cluster T3 included mostly older participants (median age, 58.2 [57.0-59.4] years) and those with the shortest asthma duration (8.1 [6.8-9.4] years). Cluster T2 participants had more participants with severe asthma (n=146), and cluster T3 participants had mostly mild-to-moderate asthma (n=163) and less atopy (62.9%). The prevalence of asthma with CRSwNP in cluster T2 was 26.6% and 25.0% in cluster T3.

In the cluster analysis of the 178 participants with asthma and CRSwNP, 3 clusters were retained and differed primarily according to inhaled corticosteroid (ICS) doses and patient age at asthma diagnosis. Cluster S1 was the largest (n=83) and included mostly participants who had mild-to-moderate asthma (n=45) with normal lung function. Cluster S2 (n=53) and cluster S3 (n=42) included participants who mostly had severe asthma (S2: n=35; S3: n=36), with high doses of ICS (S2: 1157 [1024-1290] mcg/day; S3:1246 [1097-1396] mcg/day).

Cluster S3 participants were older (59.5 [55.5-63.4] years) with an older age at asthma diagnosis (47.7 [43.5-52.0] years), and cluster S2 participants had a younger age of diagnosis (14.8 [11.1-18.4] years). Cluster S2 had the highest prevalence of atopy (86.8%) and the longest asthma duration (33.4 [30.2-36.6] years). Clusters S2 and S3 had reduced lung function, and all 3 clusters had high sputum eosinophils, with the highest percentage in cluster S3 (26.1%).

Study limitations include the retrospective analysis, and some variables were missing data for imputation. In addition, the molecular mechanisms were not assessed, and the analysis was done in patients from a tertiary care center, which could have introduced a referral bias. Also, a diagnosis of CRSwNP was based on objective observation of endoscopically visible bilateral polyps.

“Treating patients with asthma and concomitant CRSwNP has been challenging physicians for several years and this may be due to the heterogeneity of the disease,” stated the researchers. “Better understanding of the subphenotypes and their underlying mechanisms may lead to optimized identification of the best targeted therapy for these patients, including recently developed biological agents, resulting in improved management and, hopefully, lower health care use and better quality of life.”

Disclosure: Financial support for this investigator-sponsored study was provided by Genzyme. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.