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Randomized Controlled Trial
. 2017 Nov 29:12:3391-3405.
doi: 10.2147/COPD.S145814. eCollection 2017.

Determinants of exacerbation risk in patients with COPD in the TIOSPIR study

Peter Ma Calverley  1 , Kay Tetzlaff  2 , Daniel Dusser  3 , Robert A Wise  4 , Achim Mueller  5 , Norbert Metzdorf  2 , Antonio Anzueto  6
Affiliations
Randomized Controlled Trial

Determinants of exacerbation risk in patients with COPD in the TIOSPIR study

Peter Ma Calverley et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Background: Exacerbation history is used to grade the risk of COPD exacerbation, but its reliability and relationship to other risk factors and prior therapy is unclear. To examine these interrelationships, we conducted a post hoc analysis of patients in the TIOSPIR trial with ≥2 years' follow-up or who died on treatment.

Patients and methods: Patients were grouped by their annual exacerbation rate on treatment into nonexacerbators, infrequent, and frequent exacerbators (annual exacerbation rates 0, ≤1, and >1, respectively), and baseline characteristics discriminating among the groups were determined. We used univariate and multivariate analyses to explore the effect of baseline characteristics on risk of exacerbation, hospitalization (severe exacerbation), and death (all causes).

Results: Of 13,591 patients, 6,559 (48.3%) were nonexacerbators, 4,568 (33.6%) were infrequent exacerbators, and 2,464 (18.1%) were frequent exacerbators; 45% of patients without exacerbations in the previous year exacerbated on treatment. Multivariate analysis identified baseline pulmonary maintenance medication as a predictive factor of increased exacerbation risk, with inhaled corticosteroid treatment associated with increased exacerbation risk irrespective of exacerbation history.

Conclusion: Our data confirm established risk factors for exacerbation, but highlight the limitations of exacerbation history when categorizing patients and the importance of prior treatment when identifying exacerbation risk.

Keywords: COPD; exacerbation; frequent exacerbators.

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Conflict of interest statement

Disclosure PMAC reports receiving consulting fees, lecture fees, and travel support from Novartis, GlaxoSmithKline, Boehringer Ingelheim, and Takeda. DD reports receiving consulting fees, lecture fees, and payment for the development of educational activities from Boehringer Ingelheim, Pfizer, Novartis, Chiesi, Nycomed, and Dey Pharma. RAW reports receiving consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ContraFect, GlaxoSmithKline, Janssen, Mylan, Novartis, Pfizer, Pulmonx, Roche, Spiration, Sunovion, Teva, Theravance, Verona, and Vertex, and grant support from Boehringer Ingelheim, Glaxo-SmithKline, and Pearl Therapeutics. KT, AM, and NM are employees of Boehringer Ingelheim, and ARA reports receiving consulting fees, lecture fees, and travel support from AstraZeneca, Boehringer Ingelheim, Forest Laboratories, GlaxoSmithKline, and Novartis and grant support from GlaxoSmithKline. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Multivariate Cox regression of time to (A) first exacerbation, (B) first hospitalization due to COPD exacerbation, and (C) death (treated set). Notes: Multivariate analyses performed separately for A, B, and C, and not all variables qualified for all three analyses, hence not all variables included in final models. mMRC breathlessness descriptions: 0, not troubled with breathlessness except with strenuous exercise; 1, troubled by shortness of breath when hurrying on the level or walking up a slight hill; 2, walks more slowly than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level; 3, stops for breath after walking about 100 yards [91.44 m] or after a few minutes on the level; 4, too breathless to leave the house or breathless when dressing or undressing. Abbreviations: Aus, Australia; BMI, body-mass index; Euro, Europe; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; mMRC, modified Medical Research Council; NZ, New Zealand.
Figure 2
Figure 2
Exacerbation rate during the trial by pretreatment exacerbation history. Notes: In patients with ≥2 years of follow-up or who died during the study. Patients with frequent exacerbations could also have a fatal exacerbation or a severe (hospitalized) exacerbation. Pretreatment exacerbations were defined as the number of exacerbations occurring in the year prior to the trial, based on the number of episodes treated with antibiotics and/or systemic corticosteroids.
Figure 3
Figure 3
Time to first exacerbation (A), hospitalization (B) or death (C) according to exacerbation rate in the year preceding the trial and ICS use at baseline. Abbreviation: ICS, inhaled corticosteroids.
See this image and copyright information in PMC

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