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New UK study finds that increasing frequency and severity of Chronic Obstructive Pulmonary Disease (COPD) exacerbations (or 'flare ups'), increases the risk of future flare-ups and death

  • The EXACOS-UK study (EXAcerbations of COPD and their OutcomeS), funded by AstraZeneca, found that increasing frequency and severity of exacerbations, also known as ‘flare-ups’, is associated with increased rates of future flare-ups and mortality in primary care COPD patients.
  • In addition, the EXACOS-UK study concludes that even one moderate flare-up increased the rate of future flare ups, illustrating that every flare-up counts.
  • The EXACOS-UK study was an observational study that included 340,515 COPD patients across the UK.

AstraZeneca, UK, 22 April 2022: The EXACOS UK study in Chronic Obstructive Pulmonary Disease (COPD), funded by AstraZeneca, has shown that an increasing frequency and severity of flare ups, or ‘exacerbations’, can increase the risk of subsequent flare ups, starting a spiral of disease progression leading to an increased risk of death.[i],[ii]

COPD is a progressive disease and places a significant burden on our healthcare systems.[iii],[iv] Over 70% of people living with COPD can experience at least one moderate or severe flare up within three years of diagnosis.[v],[vi] It is the second largest cause of emergency hospital admissions in the UK[vii], with recorded admission rates higher than the majority of other European countries[viii], and an overall burden costing the NHS £1.9 billion a year.[ix],[x]  COPD is also the fifth most common cause of death in the UK, causing nearly 30,000 deaths every year in England alone.[xi] However, if best practice was applied, one quarter of these deaths could be avoided. Despite this, significant clinical inertia exists, leaving many patients under-treated and at greater risk of further disease progression.[xii] For example, one third of patients (33.3%) are not reviewed by a respiratory team within 24 hours of hospital admission, and 38% of patients remain under treated post hospital discharge.[xiii],[xiv] There are also challenges from a patient perspective, with 39% of patients taking no immediate action when having a flare up.[xv]

Commenting on the study findings, Carol Stonham MBE, Respiratory Senior Nurse Practitioner, NHS Gloucestershire CCG and Executive Chair of the Primary Care Respiratory Society said: “This study highlights the importance of each and every COPD exacerbation. Ultimately, every exacerbation counts. Due to existing treatment guidelines, too often we wait for patients to get worse or have a flare up before we optimise their treatment – this is a failure-based approach and must change. More needs to be done to ensure the system is set up to enable a proactive, preventative approach to allow for more ambitious treatment goals, like reducing the mortality risk.”

“The EXACOS study is a step forward in our understanding of the impact of COPD flare ups for patients in the UK” said Yang Xu, Head of Medical Affairs, Respiratory at AstraZeneca UK. “We have evidence to demonstrate that even a single moderate event increases the risk of future events.  Furthermore, a history of increased frequency and severity of flare ups was associated with an increased risk of future flare ups and death. This makes the case for a more proactive approach to prevent every flare up, even moderate ones, which will require system wide changes in COPD care. It is also vital that people are aware of the importance of seeing their doctor if they have a flare up. We welcome the opportunity to collaborate with patient groups, clinicians and the NHS to achieve the best outcomes for people with COPD.”

[i] Whittaker H, Rubino A, Müllerová H, Morris T, Varghese P, Xu Y, De Nigris E, Quint JK. Frequency and Severity of Exacerbations of COPD Associated with Future Risk of Exacerbations and Mortality: A UK Routine Health Care Data Study. Int J Chron Obstruct Pulmon Dis. 2022 Mar 3;17:427-437. doi: 10.2147/COPD.S346591. PMID: 35264849; PMCID: PMC8901192

[ii] Rothnie KJ, Müllerová H, Smeeth L, et al. Natural history of chronic obstructive pulmonary disease exacerbations in a general practice–based population with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;198(4):464–471. doi:10.1164/rccm.201710-2029OC

[iii] Srivastava K, Thakur D, Sharma S, et al. Systematic review of humanistic and economic burden of symptomatic chronic obstructive pulmonary disease. Pharmacoeconomics. 2015;33(5):467-88. CrossrefMedlineGoogle Scholar

[iv] Palli SR, Zhou S, Shaikh A, Willey VJ. Effect of compliance with GOLD treatment recommendations on COPD health care resource utilization, cost, and exacerbations among patients with COPD on maintenance therapy. J Manag Care Spec Pharm. 2021;27:625–37

[v] Hoogendoorn M, et al. Int J Chron Obstruct Pulmon Dis. 2017; 12:3183-3194.

[vi] Hurst JR, et al. N Engl J Med 2010;363:1128–1138

[vii] NICE, Health and social care directorate Quality standards and indicators Briefing paper NICE Health and social care directorates Briefing Paper, Quality standard topic: Chronic obstructive pulmonary disease (COPD) update Output: Prioritised quality improvement areas for development. Date of Quality Standards Advisory Committee meeting: 20 May 2015. Available here:,be%20readmitted%20within%20three%20months. Accessed: April 2022

[viii] Avoidable hospital admissions | Health at a Glance: Europe 2020 : State of Health in the EU Cycle | OECD iLibrary (

[ix] British Lung Foundation. The battle for breath – the economic burden of lung disease. Available at: (Accessed October 2021)

[x] Lane ND, et al. BMJ Open Respir Res 2018;5:e000334

[xi] NICE. Resource Impact Report: Chronic obstructive pulmonary disease in over 16s: diagnosis and management. 2018. Available at: https://www.nice. (Accessed October 2021)

[xii] Primary Care Respiratory Society, the British Lung Foundation, the Association of Respiratory Nurse Specialists, the Association of Chartered Physiotherapists in Respiratory Care and the National Pharmacy Association, AstraZeneca, MHP Communications. Available here: (accessed April 2022)

[xiii] National Asthma and Chronic Obstructive Pulmonary Disease Audit Programme (NACAP). COPD Clinical Audit 2019/20. June 2021. Available at: COPD+Clinical+Audit+2019-20/$File/NACAP_COPD_SC_Data_And_ Methodology_Report_2019-20_Jun_2021.pdf (Accessed October 2021)

[xiv] Jansen C, et al. Int J Chron Obstruct Pulmon Dis 2020;15:2673–2682.

[xv] Barnes N et al. BMC Pulm Med. 2013;13:54.

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Last Updated: 26-Apr-2022