Understanding low COPD exacerbation rates in Japan: a review and comparison with other countries

Abstract

COPD is associated with significant morbidity and is one of the leading causes of death worldwide. Periods of exacerbation, the acute worsening of symptoms, are interspersed throughout the disease’s natural history and can result in increased treatment burden and hospitalization for patients with COPD. The frequency of exacerbations varies between countries, with both epidemiological studies and randomized controlled trials (RCTs) showing significant differences in observed prevalence rates. Differences in study design and the healthcare setting are likely to contribute to differences in exacerbation frequency, however the perceived rate of exacerbations in Japan is currently lower then the rest of the world. This review identified nine cohort studies and five RCTs that reported COPD annual exacerbation rates in Japan in the ranges of 0.1–2.1 and 0.33–1.79, respectively. The difference in exacerbation rate between studies appeared greater than the difference between Japan and Western countries, likely because of disparities between settings, design, and inclusion criteria. Of these, only one (Understanding the Long-Term Impacts of Tiotropium) had uniform inclusion criteria across different regions. This study found that the annual rate of exacerbation events per patient in Japan was 0.61, compared with 0.85 worldwide in the placebo groups. This review summarizes the published rates of COPD exacerbations in Japan and the rest of the world and explores the hypotheses as to why rates in Japan might be lower than other countries. These include access to medical care, variance in the associated morbidity profile, environmental factors, diagnostic crossover with related diseases, and differences in study design (including the underreporting of COPD exacerbations in Japan). Understanding the reasons why COPD exacerbation rates appear lower in Japan could help clinicians to recognize and modify treatment behaviors, which may lead to improved patient outcomes in all populations.

Keywords:

• COPD
• exacerbation rate
• asthma-COPD overlap
• Japan

Supplementary materials

Table S1 Summary of key study design information from cohort studies detailing COPD exacerbation rates in Japan^1–9

Table S2 Summary of key study design information from RCTs detailing COPD exacerbation rates in Japan^10–14

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Acknowledgments

Editorial support (in the form of literature searches, writing assistance during development of the first and subsequent drafts, assembling tables and figures, collating authors comments, grammatical editing, and referencing) was provided by Elizabeth Hutchinson, PhD, CMPP, of Fishawack Indicia Ltd, UK, funded by GlaxoSmithKline (GSK). Editorial support costs associated with preparation of this paper were funded by GSK.

Author contributions

All the authors were involved in reviewing and developing the drafts for publication and approved the final version to be submitted. TI, MN, and PJ contributed equally to the manuscript development. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

TI, AA, MJ, and PJ are employees of GlaxoSmithKline (GSK) and hold stock/shares in GSK. MN has received research grants from Nippon Boehringer Ingelheim, AstraZeneca, and Novartis Japan, as well as personal fees from Nippon Boehringer Ingelheim. The authors report no other conflicts of interest in this work.