@article{93514049767c416695d07d2045d260dc,
title = "Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study",
abstract = "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.",
keywords = "Asthma, Biomarkers, Longitudinal stability, Phenotypes, Profiling, Severity",
author = "{The ADEPT Investigators} and Silkoff, {P. E.} and M. Laviolette and D. Singh and FitzGerald, {J. M.} and S. Kelsen and V. Backer and C. Porsbjerg and Girodet, {P. O.} and P. Berger and Kline, {J. N.} and S. Khatri and P. Chanez and Susulic, {V. S.} and Barnathan, {E. S.} and F. Baribaud and Loza, {M. J.} and I. Strambu and S. Lam and A. Eich and A. Ludwig-Sengpiel and Hupp, {G. C.} and R. Leigh and M. Dransfield and W. Calhoun and A. Hussaini and Francisco Leon and Keith Lasher and Jennifer Campos and Debra Alvarez and Robert Gordon and Hongjuan Liu and Dipti Shah and Jennifer Montello and Filza Potapova",
note = "Funding Information: I Strambu1, S Lam2, A Eich3, A Ludwig-Sengpiel4, G C hupp5, R Leigh6, M Dransfield7, W Calhoun8, A Hussaini9 1Arensia Exploratory Medicine, Sos. Viilor 90, Bucharest 050159, Romania. Email: irina.strambu@arensia-em.com 2Institute for Heart and Lung Health, The Lung Centre, 7th Floor, Gordon and Leslie Diamond Health Care Centre, 2775 Laurel Street, Vancouver, B.C., Canada, V5Z 1 M9. Email: mark.fitzgerald@vch.ca, slam2@bccancer.bc.ca 3IKF Pneumologie Frankfurt, Institut f{\"u}r klinische Forschung Pneumologie, Clinical Research Centre Respiratory Diseases, Schaumainkai 101-103, Strese-mannallee 360596, Frankfurt, Germany. Email: eich@ikf-pneumologie.de 4KLB Gesundheitsforschung L{\"u}beck GmbH, Sandstr. 18, 23552 L{\"u}beck, Germany. Email: A.Ludwig@klb-healthresearch.com 5Yale Center for Asthma and Airway Disease, Division of Pulmonary and Critical Care and Sleep Medicine, Yale School of Medicine, TAC 441, 300 Cedar Street, New Haven CT, 06520 Email: geoffrey.chupp@yale.edu 6Cumming Scholl of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada. Email: rleigh@ucalgary.ca 7Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham & Birmingham VA Medical Center, 422 THT, 1900 University Blvd, Birmingham, AL 35294, USA. Email: mdrans99@uab.edu 84.116 John Sealy Annex, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555-0568, USA: Email: William.Calhoun@utmb.edu 9Parexel International, Shelton Simmons (MD), 3001 S Hanover St #7, Brooklyn, MD 21225, USA. Email: Azra.Hussaini@parexel.com The following Janssen personnel contributed significantly to the success of ADEPT: Francisco Leon, Keith Lasher, Jennifer Campos, Debra Alvarez, Robert Gordon, Hongjuan Liu, Dipti Shah, Jennifer Montello, Filza Potapova. Regarding Dr. D Singh{\textquoteright}s participation, this report is independent research carried out and supported by the National Institute for Health Research (NIHR) South Manchester Respiratory and Allergy Clinical Research Facility at University Hospital of South Manchester NHS Foundation Trust. The views expressed in this publication are those of the author and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. Publisher Copyright: {\textcopyright} 2016 Silkoff et al.",
year = "2016",
doi = "10.1186/S12931-016-0360-5",
language = "English (US)",
volume = "17",
pages = "1--12",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",
number = "1",
}