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

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

NCT1126437.

Keywords:

• TIOSPIR
• tiotropium
• HandiHaler
• Respimat Soft Mist inhaler
• seasonality
• preventive treatment
• exacerbations

Acknowledgments

This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. The authors received no direct compensation related to the development of the manuscript. Writing and editorial support was provided by Jane M Gilbert BSc CMPP of Envision Scientific Solutions, which was contracted and funded by BIPI. An abstract of this article was presented as an oral presentation at Chest 2014, October 25–30, 2014, Austin, TX, USA, and the abstract was published in Chest. 2014;146(4, Suppl 2):66A.

Disclosure

RAW reports personal fees and grants from Boehringer Ingelheim during the conduct of the study. He reports personal fees from AstraZeneca, Boehringer Ingelheim, ContraFect, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Pulmonx, Roche, Spiration, Sunovion, Teva, Theravance, Verona, and Vertex; and grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Pearl Therapeutics outside the submitted work. PMAC reports grants and personal fees from GlaxoSmithKline and Takeda; personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, Zambon, and Recipharm; and non-financial support from Boehringer Ingelheim outside the submitted work. KC and EC-B are employees of Boehringer Ingelheim Pharmaceuticals, Inc. NM is an employee of Boehringer Ingelheim Pharma GmbH & Co KG. AA reports grants and personal fees from GlaxoSmithKline, and personal fees from AstraZeneca, Boehringer Ingelheim, and Novartis outside the submitted work. The authors report no other conflicts of interest in this work.

Author contributions

The authors meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). RAW was the coordinating investigator for the TIOSPIR trial. PMAC and AA were members of the trial steering committee. KC was the co-trial statistician. EC-B contributed to the conduct of the trial. Conception and design: RAW, PMAC, NM, and AA. Acquisition, analysis, and interpretation of data: RAW, PMAC, KC, EC-B, NM, and AA. Drafting and revision of the manuscript: RAW, PMAC, KC, EC-B, NM, and AA. All authors contributed to the intellectual content of the manuscript, reviewed drafts of the manuscript, and approved the manuscript version submitted for publication.