Journal article
Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study
Respiratory research, Vol.17(1), pp.1-12
2016
DOI: 10.1186/s12931-016-0360-5
PMCID: PMC4842260
PMID: 27107814
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.
Details
- Title: Subtitle
- Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study
- Creators
- P. E Silkoff - Janssen Research & Development LLC, Spring House, PA USAM Laviolette - Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ), 2725, Chemin Ste-Foy, Quebec, QC G1V 4G5 CanadaD Singh - Centre for Respiratory Medicine and Allergy, the University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester NHS Foundation Trust, Southmoor Road, Manchester, M23 9QZ UKJ. M FitzGerald - Institute for Heart and Lung Health, The Lung Centre, Gordon and Leslie Diamond Health Care Centre, 7th Floor, 2775 Laurel Street, Vancouver, BC V5Z 1M9 CanadaS Kelsen - Department of Thoracic Medicine and Surgery, Temple University School of Medicine, 401N. Broad St., Philadelphia, PA 19140 USAV Backer - Respiratory Research Unit, Department of Respiratory Medicine, Bispebjerg University Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, NV DenmarkC Porsbjerg - Respiratory Research Unit, Department of Respiratory Medicine, Bispebjerg University Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, NV DenmarkP. O Girodet - Centre de Recherche Cardio-Thoracique de Bordeaux, University of Bordeaux, U1045, CIC 1401, F-33000 Bordeaux, FranceP Berger - Centre de Recherche Cardio-Thoracique de Bordeaux, University of Bordeaux, U1045, CIC 1401, F-33000 Bordeaux, FranceJ. N Kline - Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa, W219B GH UIHC, 200 Hawkins Drive, Iowa City, IA 52242 USAS Khatri - Department of Pulmonary and Critical Care, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 USAP Chanez - Pneumologie, Aix Marseille University, APHM/INSERM U1067, Chemin des Bourellys 13015, Marseille, FranceV. S Susulic - Janssen Research & Development LLC, Spring House, PA USAE. S Barnathan - Janssen Research & Development LLC, Spring House, PA USAF Baribaud - Janssen Research & Development LLC, Spring House, PA USAM. J Loza - Janssen Research & Development LLC, Spring House, PA USAADEPT Investigators
- Resource Type
- Journal article
- Publication Details
- Respiratory research, Vol.17(1), pp.1-12
- DOI
- 10.1186/s12931-016-0360-5
- PMID
- 27107814
- PMCID
- PMC4842260
- NLM abbreviation
- Respir Res
- ISSN
- 1465-9921
- eISSN
- 1465-993X
- Publisher
- BioMed Central
- Grant note
- ;
- Language
- English
- Date published
- 2016
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Occupational and Environmental Health; Internal Medicine
- Record Identifier
- 9984094620502771
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