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Respir Res. 2016 Apr 23;17:43. doi: 10.1186/s12931-016-0360-5.

Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study.

Author information

1
Janssen Research & Development LLC, Spring House, PA, USA. philsilkoff@gmail.com.
2
, Present Address: 715 Bryn Mawr Avenue, Penn Valley, PA, 19072, USA. philsilkoff@gmail.com.
3
Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ), 2725, Chemin Ste-Foy, Quebec, QC, G1V 4G5, Canada.
4
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, UK.
5
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, Canada.
6
Department of Thoracic Medicine and Surgery, Temple University School of Medicine, 401N. Broad St., Philadelphia, PA, 19140, USA.
7
Respiratory Research Unit, Department of Respiratory Medicine, Bispebjerg University Hospital, Bispebjerg bakke 23, DK-2400, Copenhagen, NV, Denmark.
8
Centre de Recherche Cardio-Thoracique de Bordeaux, University of Bordeaux, U1045, CIC 1401, F-33000, Bordeaux, France.
9
Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa, W219B GH UIHC, 200 Hawkins Drive, Iowa City, IA, 52242, USA.
10
Department of Pulmonary and Critical Care, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
11
Pneumologie, Aix Marseille University, APHM/INSERM U1067, Chemin des Bourellys 13015, Marseille, France.
12
Janssen Research & Development LLC, Spring House, PA, USA.

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

PMID:
27107814
PMCID:
PMC4842260
DOI:
10.1186/s12931-016-0360-5
[Indexed for MEDLINE]
Free PMC Article

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