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

Abstract

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.

Conflict of interest statement

Ethics approval and consent to participate

The study was performed in accordance with the Declaration of Helsinki, the International Conference on Harmonisation’s Harmonised Tripartite Guideline for Good Clinical Practice and local regulations. The protocol was approved by the ethics research board of the respective institutions.

Consent for publication

Not applicable.

Competing interests

HW reports that his institute was reimbursed by Boehringer Ingelheim for the conduct of the study, and he received personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Roche outside the submitted work. HM reports personal fees from AstraZeneca, Boehringer Ingelheim, Novartis and ndd Medical Technologies during the conduct of the study. RR-R reports personal fees from AstraZeneca, Boehringer Ingelheim and Pearl Therapeutics outside the submitted work. EFMW reports personal fees from Boehringer Ingelheim, Nycomed, AstraZeneca, GlaxoSmithKline, Novartis and Chiesi. CV reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Mundipharma, Novartis and Takeda, personal fees from Almirall, Cipla, Berlin-Chemie/Menarini, CSL Behring and Teva, and grants from the German Federal Ministry of Education and Research’ (BMBF) Competence Network Asthma and COPD (ASCONET), Bayer Schering Pharma AG, MSD and Pfizer outside the submitted work. PMAC reports grants and personal fees from GlaxoSmithKline and Takeda, personal fees from AstraZeneca and Novartis, and personal fees and non-financial support from Boehringer Ingelheim outside the submitted work.

KT and AM are employees of Boehringer Ingelheim.

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Figures

Fig. 1

a Percentage change from period baseline in on-treatment daily FEV1 before and after first moderate/severe exacerbation. b Percentage change from period baseline in on-treatment daily FEV1 before and after first moderate exacerbation. c Percentage change from period baseline in on-treatment daily FEV1 before and after first severe exacerbation. All graphs show both treatments combined. Plots include patients whose first exacerbation after the ICS withdrawal visit was neither preceded by an exacerbation of any severity in 8 weeks prior nor followed by a further exacerbation of any severity within 8 weeks (56 days) after exacerbation. Day 0 is the day of the exacerbation. Period baseline is the mean of Days − 56 to − 36. FEV1, forced expiratory volume in 1 s; ICS, inhaled corticosteroids; SE, standard error

Fig. 2

FEV1 before, during and after moderate/severe exacerbations, moderate exacerbations and severe exacerbations. FEV1, forced expiratory volume in 1 s

Fig. 3

a Change from Week − 8 in on-treatment weekly FEV1 before and after first moderate/severe exacerbation. b Change from Week − 8 in on-treatment weekly FEV1 before and after first moderate exacerbation. c Change from Week − 8 in on-treatment weekly FEV1 before and after first severe exacerbation. All graphs show both treatments combined. Plots include patients whose first exacerbation after the ICS withdrawal visit was neither preceded by an exacerbation of any severity in 8 weeks prior nor followed by a further exacerbation of any severity within 8 weeks (56 days) after exacerbation. Patients had weekly means available for the entire period of interest. FEV1, forced expiratory volume in 1 s; ICS, inhaled corticosteroids; SE, standard error

Fig. 4

Percentage change from period baseline in on-treatment daily FEV1 before and after first exacerbation by treatment group. Plot includes patients whose first moderate or severe exacerbation after the ICS withdrawal visit was neither preceded by an exacerbation of any severity in 8 weeks prior nor followed by a further exacerbation of any severity within 8 weeks (56 days) after exacerbation. Day 0 is the day of the exacerbation. Period baseline is the mean of Days − 56 to − 36. FEV1, forced expiratory volume in 1 s; ICS, inhaled corticosteroids; SE, standard error