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

Sci Rep. 2020 Oct 15;10(1):17415. doi: 10.1038/s41598-020-72551-0.


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: registration number NCT01351792 (registration date May 11, 2011), registration number NCT00848406 (registration date February 20, 2009), registration number NCT00158847 (registration date September 12, 2005).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Aged
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Budesonide / administration & dosage
  • Budesonide / therapeutic use*
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Female
  • Formoterol Fumarate / administration & dosage
  • Formoterol Fumarate / therapeutic use*
  • Gene Expression Profiling*
  • Humans
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Nasal Cavity / metabolism*
  • Placebos
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology


  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Placebos
  • Budesonide
  • Formoterol Fumarate

Associated data