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

Abstract

BackgroundAlthough 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 methodsTIOSPIR 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.ResultsTIOSPIR 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.ConclusionAlthough 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 numberNCT01126437.

A time for everything and everything in its time – exploring the mechanisms underlying seasonality of COPD exacerbations

“…Allowing for this variation, a systematic search, on the PubMed and Embase libraries, using the search terms of “seasonality” and “COPD exacerbations” identified seven separate studies showing a seasonal variation in COPD exacerbations. 9 , 10 , 14 – 19 A large international multicenter study, the TORCH trial, has shown that seasonality in temperate climates increases the rate of exacerbations, with an almost twofold increase in winter compared with summer months. 9 This is further supported by extrapolation of results from the POET-COPD study which documented a 116% increase in exacerbation rates from December to February when compared with June to August in a study of 7,376 patients over 12 months.…”

Trends and seasonal variation of hospitalization and mortality of interstitial lung disease in the United States from 2006 to 2016

“…All of those conditions also have been reported to have higher mortality in winter time in the general population [12,22], which may explain the higher mortality in IPF and non IPF ILD patients in winter time Of note, the in-hospital mortality of interstitial lung disease was noted to be significantly higher than the similar study in chronic obstructive lung disease (COPD) and asthma patients using the same national database ,8% vs 2%, 8% vs 1% respectively [23,24]. interestingly enough, the mortality rate was 14% higher in the winter compared to the summer, which was less pronounced than the seasonal variations of all cause of deaths of COPD patients (25% to 50% higher in the winter) [12,25].…”

Trends and seasonal variation of hospitalization and mortality of interstitial lung disease in the United States from 2006 to 2016.

“…All of those conditionsalso have been reported to have higher mortality in winter time inthe general population [12,22], which may explain the highermortality in IPF and non IPF ILD patients in winter time Of note, the in-hospital mortality of interstitial lung diseasewas noted to be signi cantly higher than the similar study inchronic obstructive lung disease (COPD) and asthma patients usingthe same national database ,8% vs 2%, 8% vs 1% respectively [23,24]. interestingly enough, the mortality rate was 14% higher in thewinter compared to the summer, which was less pronounced than theseasonal variations of all cause of deaths of COPD patients (25% to50% higher in the winter) [12,25]. Although both COPD andinterstitial lung disease are both progressive illnesses with thepathogenesis involving accelerated cellular senescence [26].…”