Seasonal variations in exacerbations and deaths in patients with COPD during the TIOSPIR ® trial

Int J Chron Obstruct Pulmon Dis. 2018 Feb 14;13:605-616. doi: 10.2147/COPD.S148393. eCollection 2018.

Abstract

Background: Although COPD exacerbations are known to occur more frequently in winter, there is little information on hospitalizations and cause-specific mortality. This study aimed to examine seasonal variations in mortality and exacerbations in patients with COPD during the TIOtropium Safety and Performance In Respimat® (TIOSPIR®) trial.

Patients and methods: TIOSPIR was a large-scale, multicenter trial, which assessed the safety and efficacy of tiotropium delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ (2.5 or 5 μg once daily) inhaler in patients with COPD. Patients were aged ≥40 years, with a smoking history ≥10 pack-years, and post-bronchodilator forced expiratory volume in 1 second ≤70% and forced expiratory volume in 1 second/forced vital capacity ≤0.70. COPD exacerbations and deaths were monitored throughout the trial. The data were pooled to examine seasonal patterns. Southern hemisphere data were shifted by 6 months to align with northern hemisphere seasons.

Results: TIOSPIR was conducted in 43 northern (n=15,968) and 7 southern (n=1,148) hemisphere (n=1,148) countries. The median duration of treatment was 835 days, with a mean follow-up of 2.3 years. Among 19,494 exacerbations, there were clear seasonal differences (winter, 6,646 [34.1%]; spring, 4,515 [23.2%]; summer, 3,198 [16.4%]; autumn, 5,135 [26.3%]). Exacerbations peaked in early winter (December in the northern hemisphere and June in the southern hemisphere), respiratory hospitalizations in midwinter, and respiratory deaths in early spring.

Conclusion: Although winter poses a 2-fold hazard for COPD exacerbations vs summer, respiratory deaths peak in early spring. These data suggest that seasonal intensification of preventive treatments may impact COPD morbidity and mortality.

Trial registration number: NCT01126437.

Keywords: HandiHaler; Respimat Soft Mist inhaler; TIOSPIR; exacerbations; preventive treatment; seasonality; tiotropium.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Aged
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Cause of Death
  • Cholinergic Antagonists / administration & dosage*
  • Cholinergic Antagonists / adverse effects
  • Disease Progression
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Nebulizers and Vaporizers
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / mortality
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Risk Factors
  • Seasons*
  • Time Factors
  • Tiotropium Bromide / administration & dosage*
  • Tiotropium Bromide / adverse effects
  • Treatment Outcome
  • Vital Capacity

Substances

  • Bronchodilator Agents
  • Cholinergic Antagonists
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT01126437