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

T Zaihra,Q A Hamid,J G Martin,S Ahmed,R Olivenstein,C Fugère,C J Walsh,A Benedetti

doi:10.1186/s12890-016-0232-2

Abstract

BackgroundAlthough 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.MethodsA 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 (FEV1 and BMI) and biomarker (sputum eosinophil count) variables, using k-means clustering.ResultsMajority 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.ConclusionAsthma 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.

Highlights

The heterogeneous nature of asthma has prompted asthma phenotyping with physiological or biomarker data, these studies have been mostly cross-sectional
One hundred twenty five subjects had a total of 593 clinician assessments at baseline, 3, 6, 9, and 12 months resulting in 593 spirometric tests, 538 exhaled nitric oxide (FENO) measurements, and 400 sputum analyses
There were no significant differences in age, age-of-onset of asthma, sex, smoking history, or atopic status between moderate and severe asthmatics

Summary

Introduction

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. Morbidity, mortality, and economic burden associated with asthma have increased over the last 40 years [1]. 300 million people worldwide currently have asthma, and its prevalence increases by 50 % every decade [1]. Heterogeneity of clinical presentation and disease mechanisms exist within asthma, frustrating attempts to achieve optimal asthma control in all subjects. Identification of asthma phenotypes, i.e. groups with unique characteristics that are stable or predictable over time, may have prognostic or therapeutic significance leading to better tailoring of subject-centered therapies

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