Phenotyping of difficult asthma using longitudinal physiological and biomarker measurements reveals significant differences in stability between clusters

BACKGROUND: Although the heterogeneous nature of asthma has prompted asthma phenotyping with physiological or biomarker data, these studies have been mostly cross-sectional. Longitudinal studies that assess the stability of phenotypes based on a combination of physiological, clinical and biomarker data are currently lacking. Our objective was to assess the longitudinal stability of clusters derived from repeated measures of airway and physiological data over a 1-year period in moderate and severe asthmatics. METHODS: A total of 125 subjects, 48 with moderate asthma (MA) and 77 with severe asthma (SA) were evaluated every 3 months and monthly, respectively, over a 1-year period. At each 3-month time point, subjects were grouped into 4 asthma clusters (A, B, C, D) based on a combination of clinical (duration of asthma), physiological (FEV(1) and BMI) and biomarker (sputum eosinophil count) variables, using k-means clustering. RESULTS: Majority of subjects in clusters A and C had severe asthma (93 % of subjects in cluster A and 79.5 % of subjects in cluster C at baseline). Overall, a total of 59 subjects (47 %) had stable cluster membership, remaining in clusters with the same subjects at each evaluation time. Cluster A was the least stable (21 % stability) and cluster B was the most stable cluster (71 % stability). Cluster stability was not influenced by changes in the dosage of inhaled corticosteroids. CONCLUSION: Asthma phenotyping based on clinical, physiologic and biomarker data identified clusters with significant differences in longitudinal stability over a 1-year period. This finding indicates that the majority of patients within stable clusters can be phenotyped with reasonable accuracy after a single measurement of lung function and sputum eosinophilia, while patients in unstable clusters will require more frequent evaluation of these variables to be properly characterized.