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

Robert A. Wise, Peter M.A. Calverley, Kerstine Carter, Emmanuelle Clerisme-Beaty, Norbert Metzdorf, Antonio Anzueto

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)605-616
Number of pages12
JournalInternational Journal of COPD
StatePublished - Feb 14 2018


  • Exacerbations
  • HandiHaler
  • Preventive treatment
  • Respimat Soft Mist inhaler
  • Seasonality
  • Tiotropium

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health Policy
  • Pulmonary and Respiratory Medicine


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