Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study

Research

P. E. Silkoff^1*, I. Strambu², M. Laviolette³, D. Singh⁴, J. M. FitzGerald⁵⁶, S. Lam⁵⁶, S. Kelsen⁷, A. Eich⁸, A. Ludwig-Sengpiel⁹, G. C hupp¹⁰, V. Backer¹¹, C. Porsbjerg¹¹, P. O. Girodet¹², P. Berger¹², R. Leigh¹³, J. N. Kline¹⁴, M. Dransfield¹⁵, W. Calhoun¹⁶, A. Hussaini¹⁷, S. Khatri¹⁸, P. Chanez¹⁹, V. S. Susulic¹, E. S. Barnathan¹, M. Curran¹, A. M. Das¹, C. Brodmerkel¹, F. Baribaud¹ and M. J. Loza¹

Respiratory Research 2015, 16:142  doi:10.1186/s12931-015-0299-y

Abstract

Background

Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This report presents for the first time the study design, and characteristics of the recruited subjects.

Methods

Patients with a range of asthma severity and healthy non-atopic controls were enrolled. The asthmatic subjects were followed for 12 months. Assessments included history, patient questionnaires, spirometry, airway hyper-responsiveness to methacholine, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum, blood, and bronchoscopy samples. All subjects underwent sputum induction and 30 subjects/cohort had bronchoscopy.

Results

Mild (n = 52), moderate (n = 55), severe (n = 51) asthma cohorts and 30 healthy controls were enrolled from North America and Western Europe. Airflow obstruction, bronchodilator response and airways hyperresponsiveness increased with asthma severity, and severe asthma subjects had reduced forced vital capacity. Asthma control questionnaire-7 (ACQ7) scores worsened with asthma severity. In the asthmatics, mean values for all clinical and biomarker characteristics were stable over 12 months although individual variability was evident. FENO and blood eosinophils did not differ by asthma severity. Induced sputum eosinophils but not neutrophils were lower in mild compared to the moderate and severe asthma cohorts.

Conclusions

The ADEPT study successfully enrolled asthmatics across a spectrum of severity and non-atopic controls. Clinical characteristics were related to asthma severity and in general asthma characteristics e.g. lung function, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches.

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