Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study.
BACKGROUND
Asthma is a biologically heterogeneous disease and development of novel therapeutics requires understanding of pathophysiologic phenotypes. There is uncertainty regarding the stability of clinical characteristics and biomarkers in asthma over time. This report presents the longitudinal stability over 12 months of clinical characteristics and clinically accessible biomarkers from ADEPT.


METHODS
Mild, moderate, and severe asthma subjects were assessed at 5 visits over 12 months. Assessments included patient questionnaires, spirometry, bronchodilator reversibility, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum.


RESULTS
Mild (n = 52), moderate (n = 55), and severe (n = 51) asthma cohorts were enrolled from North America and Western Europe. For all clinical characteristics and biomarkers, group mean data showed no significant change from visit to visit. However, individual data showed considerable variability. FEV1/FVC ratio showed excellent reproducibility while pre-bronchodilator FEV1 and FVC were only moderately reproducible. Of note bronchodilator FEV1 reversibility showed low reproducibility, with the nonreversible phenotype much more reproducible than the reversible phenotype. The 7-item asthma control questionnaire (ACQ7) demonstrated moderate reproducibility for the combined asthma cohorts, but the uncontrolled asthma phenotype (ACQ7 > 1.5) was inconstant in mild and moderate asthma but stable in severe asthma. FENO demonstrated good reproducibility, with the FENO-low phenotype (FENO < 35 ppb) more stable than the FENO-high phenotype (FENO ≥ 35 ppb). Induced sputum inflammatory phenotypes showed marked variability across the 3 sputum samples taken over 6 months.


CONCLUSIONS
The ADEPT cohort showed group stability, individual stability in some parameters e.g. low FEV1/FVC ratio, and low FENO, but marked individual variability in other clinical characteristics and biomarkers e.g. type-2 biomarkers over 12 months. This variability is possibly related to seasonal variations in climate and allergen exposure, medication changes and acute exacerbations. The implications for patient selection strategies based on clinical biomarkers may be considerable.
['Silkoff|P E|PE|', 'Laviolette|M|M|', 'Singh|D|D|', 'FitzGerald|J M|JM|', 'Kelsen|S|S|', 'Backer|V|V|', 'Porsbjerg|C|C|', 'Girodet|P O|PO|', 'Berger|P|P|', 'Kline|J N|JN|', 'Khatri|S|S|', 'Chanez|P|P|', 'Susulic|V S|VS|', 'Barnathan|E S|ES|', 'Baribaud|F|F|', 'Loza|M J|MJ|', '|||']
D000328:Adult D001249:Asthma D015415:Biomarkers D001993:Bronchodilator Agents D005060:Europe D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D009656:North America D015995:Prevalence D015203:Reproducibility of Results D012129:Respiratory Function Tests D012307:Risk Factors D012680:Sensitivity and Specificity D012720:Severity of Illness Index D013183:Sputum D016896:Treatment Outcome
Longitudinal stability Asthma Biomarkers Phenotypes Severity Profiling