Identifying a nasal gene expression signature associated with hyperinflation and treatment response in severe COPD

Alen Faiz, Kai Imkamp*, Erica van der Wiel, Ilse M Boudewijn, Gerard H Koppelman, Corry-Anke Brandsma, Huib A M Kerstjens, Wim Timens, Sebastiaan Vroegop, Henk R Pasma, Wim G Boersma, Pascal Wielders, Frank van den Elshout, Khaled Mansour, Katrina Steiling, Avrum Spira, Marc E Lenburg, Irene H Heijink, Dirkje S Postma, Maarten van den Berge

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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Hyperinflation contributes to dyspnea intensity in COPD. Little is known about the molecular mechanisms underlying hyperinflation and how inhaled corticosteroids (ICS) affect this important aspect of COPD pathophysiology. To investigate the effect of ICS/long-acting β2-agonist (LABA) treatment on both lung function measures of hyperinflation, and the nasal epithelial gene-expression profile in severe COPD. 117 patients were screened and 60 COPD patients entered a 1-month run-in period on low-dose ICS/LABA budesonide/formoterol (BUD/F) 200/6 one inhalation b.i.d. Patients were then randomly assigned to 3-month treatment with either a high dose BDP/F 100/6 two inhalations b.i.d. (n = 31) or BUD/F 200/6 two inhalations b.i.d. (n = 29). Lung function measurements and nasal epithelial gene-expression were assessed before and after 3-month treatment and validated in independent datasets. After 3-month ICS/LABA treatment, residual volume (RV)/total lung capacity (TLC)% predicted was reduced compared to baseline (p < 0.05). We identified a nasal gene-expression signature at screening that associated with higher RV/TLC% predicted values. This signature, decreased by ICS/LABA treatment was enriched for genes associated with increased p53 mediated apoptosis was replicated in bronchial biopsies of COPD patients. Finally, this signature was increased in COPD patients compared to controls in nasal, bronchial and small airways brushings. Short-term ICS/LABA treatment improves RV/TLC% predicted in severe COPD. Furthermore, it decreases the expression of genes involved in the signal transduction by the p53 class mediator, which is a replicable COPD gene expression signature in the upper and lower airways.Trial registration: ClinicalTrials.gov registration number NCT01351792 (registration date May 11, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 20, 2009), ClinicalTrials.gov registration number NCT00158847 (registration date September 12, 2005).

Originele taal-2English
Artikelnummer17415
Pagina's (van-tot)1-12
Aantal pagina's12
TijdschriftScientific Reports
Volume10
Nummer van het tijdschrift1
DOI's
StatusPublished - 15-okt-2020

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