Spirometric changes during exacerbations of COPD: a post hoc analysis of the WISDOM trial

Respir Res. 2018 Dec 13;19(1):251. doi: 10.1186/s12931-018-0944-3.


Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function and poor outcomes for patients. However, there are limited data on the time course of changes in forced expiratory volume in 1 s (FEV1) preceding the first reported symptom and after the start of an exacerbation.

Methods: WISDOM was a multinational, randomized, double-blind, active-controlled, 52-week study in patients with severe-to-very severe COPD. Patients received triple therapy (long-acting muscarinic antagonist and long-acting β2-agonist/inhaled corticosteroid [ICS]) for 6 weeks, and were randomized to continue triple therapy or stepwise withdrawal of the ICS (dual bronchodilator group). After suitable training, patients performed daily spirometry at home using a portable, battery-operated spirometer. In the present post hoc analysis, patients who continued to perform daily home spirometry and completed at least one measurement per week for a 56-day period before and after the start of a moderate or severe exacerbation were included. Missing values were imputed by linear interpolation (intermittent), backfilling (beginning) or carry forward (end). Exacerbation onset was the first day of a reported symptom of exacerbation.

Results: Eight hundred and eighty-eight patients in the WISDOM study had a moderate/severe exacerbation after the complete ICS withdrawal visit; 360 of them contributed at least one FEV1 measure per week for the 8 weeks before and after the event and are included in this analysis. Mean daily FEV1 began to decline from approximately 2 weeks before the onset of symptoms of an exacerbation, dropping from 0.907 L (mean Days - 56 to - 36 before the exacerbation) to 0.860 L on the first day of the exacerbation. After the exacerbation, mean FEV1 improved but did not return to pre-exacerbation levels (mean Days 36-56 after the exacerbation, 0.875 L). The pattern of FEV1 changes around exacerbations was similar in the triple therapy and dual bronchodilator groups, and a similar pattern was seen in moderate and severe exacerbations when analysed separately.

Conclusions: Mean lung function starts to decline prior to the first reported symptoms of an exacerbation, and does not recover to pre-exacerbation levels 8 weeks after the event.

Trial registration: WISDOM (ClinicalTrials.gov number, NCT00975195 ).

Keywords: COPD; COPD exacerbation; FEV1; Home-based spirometry; Lung function.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Aged
  • Bronchodilator Agents / administration & dosage
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fluticasone / administration & dosage
  • Forced Expiratory Volume / drug effects
  • Forced Expiratory Volume / physiology*
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Salmeterol Xinafoate / administration & dosage
  • Spirometry / trends*
  • Tiotropium Bromide / administration & dosage


  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Muscarinic Antagonists
  • Salmeterol Xinafoate
  • Fluticasone
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT00975195