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. 2022 Mar 3:17:427-437.
doi: 10.2147/COPD.S346591. eCollection 2022.

Frequency and Severity of Exacerbations of COPD Associated with Future Risk of Exacerbations and Mortality: A UK Routine Health Care Data Study

Hannah Whittaker  1 , Annalisa Rubino  2 , Hana Müllerová  2 , Tamsin Morris  3 , Precil Varghese  4 , Yang Xu  3 , Enrico De Nigris  5 , Jennifer K Quint  1
Affiliations

Frequency and Severity of Exacerbations of COPD Associated with Future Risk of Exacerbations and Mortality: A UK Routine Health Care Data Study

Hannah Whittaker et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Background: Studies have shown that chronic obstructive pulmonary disease (COPD) exacerbation events are related to future events; however, previous literature typically reports frequent vs infrequent exacerbations per patient-year and no studies have investigated increasing number of severe exacerbations in relation to COPD outcomes.

Objective: To investigate the association between baseline frequency and severity of exacerbations and subsequent mortality and exacerbation risk in a COPD cohort.

Methods: Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics data were used to identify patients registered at general practices in the UK, who had a diagnosis of COPD, were over the age of 40 years, were smokers or ex-smokers and had data recorded from 2004 onwards. Frequency and severity of exacerbations in the baseline year were identified as moderate exacerbations (general practice events) and severe exacerbations (hospitalised events). Patients were categorised as having: none, 1 moderate only, 2 moderate only, 3+ moderate only, 1 severe (and any moderate), 2 severe (and any moderate), and 3+ severe (and any moderate exacerbations). Poisson regression was used to investigate the association between baseline exacerbation frequency/severity and exacerbation events and mortality over follow-up.

Results: Overall, 340,515 COPD patients were included. Patients had higher rates of future exacerbations with increasing frequency and severity of baseline exacerbations compared to no baseline exacerbations. Adjusted incidence rate ratios (IRR) for patients with 1, 2, and 3+ moderate exacerbations compared to 0 exacerbations were 1.70 (95% CI 1.66-1.74), 2.31 (95% CI 2.24-2.37), and 3.52 (95% CI 3.43-3.62), respectively. Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion.

Conclusion: Increasing number and severity of exacerbations were associated with increasing risk of subsequent exacerbations, all-cause mortality and COPD-related mortality. Even a single moderate event increases the risk of future events, illustrating that every exacerbation counts.

Keywords: COPD; exacerbations of COPD.

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Conflict of interest statement

JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, AUK-BLF, Chiesi, and AZ, and personal fees for advisory board participation or speaking fees from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca and Bayer. HW has nothing to disclose. AR, HM, TM, and YX are employees of AstraZeneca and holds stock and/or options in the company. PV and EdN are both former employees of AstraZeneca, but were employed by AstraZeneca at the time of the study. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Incidence rate ratios (IRR) for the association between baseline frequency and severity of exacerbations and rate of (A) any future exacerbations, (B) moderate exacerbations, and (C) severe exacerbations.
Figure 3
Figure 3
Incidence rate ratios (IRR) for the association between baseline frequency and severity of exacerbations and rate of (A) all-cause mortality, (B) COPD-related mortality, and (C) CVD-related mortality.
See this image and copyright information in PMC

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