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Reducing exacerbations in COPD


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Strategies by which pharmacists can support patients in minimising the risk of exacerbations in chronic obstructive pulmonary disease, and ways to optimise self-management and overall control of this condition are discussed
Hetal Dhruve MPharmS PG Dip GPP
Specialist Clinical Pharmacist – 
Respiratory and Allergy
Hasanin Khachi MPharmS ClinDip IPresc MBA
Lead Respiratory Pharmacist
Barts Health NHS Trust, London UK
Chronic obstructive pulmonary disease (COPD) is an umbrella term used to describe irreversible respiratory conditions that include emphysema and chronic bronchitis. It is characterised by airflow obstruction which is present as a result of long-term exposure to noxious particles or gas and for the majority of patients, it is a due to smoking tobacco.1,2 Patients with COPD have airway and parenchymal damage; a result of chronic inflammation and differs from that seen in asthma. Consequently, patients with COPD usually present with symptoms of dyspnoea, chronic cough and chronic sputum production and are most often aged over 35 years.1
COPD affects an estimated three million people in the UK and remains a major health problem. Currently, COPD is the fifth biggest killer in the UK, accounting for 25,000 deaths in England and Wales. The World Health Organization, however, estimates that by 2030, COPD will become the third leading cause of death. Furthermore, it is the second most common cause of emergency admissions to hospital.3
COPD is a leading cause of morbidity and mortality worldwide and is associated with an increasing incidence of exacerbations.3 An exacerbation of COPD is defined by a rapid and sustained worsening of symptoms beyond normal day-to-day variations; characterised by a change in the patient’s baseline dyspnoea, cough and sputum purulence and/or colour. An exacerbation is associated with worsening of airflow obstruction and its severity is based on clinical symptoms. Each exacerbation results in a more rapid decline of lung function and contributes to disease progression, decreased quality of life and increased mortality.3–5 There are also significant costs incurred to treat exacerbations and the associated cost tends to increase as the disease progresses.3
Precipitated by various factors, exacerbations may be due to aspects such as viral or bacterial upper respiratory tract infections and infection of the tracheobronchial tree.2 Acute exacerbations require frequent medical evaluation and increase the utilisation of health resources, requiring emergency and hospital admissions, especially in those patients with a poor health status.4 Those who frequently exacerbate have worse health-related quality of life.6
Mild exacerbations require increased doses of bronchodilators, such as salbutamol, whereas moderate to severe exacerbations require treatment with systemic corticosteroids, antibiotics or both and/or admission into hospital or A&E attendance, respectively. Usually the frequency of exacerbations increases as the severity of COPD progresses. Exacerbations increase the rate of lung function decline and impact quality of life.6,7 The primary goal of treatment in COPD is to reduce symptoms, reduce the frequency and severity of exacerbations and improve health status and exercise tolerance.3
There are several strategies that can be employed to achieve this; these include smoking cessation, pulmonary rehabilitation, appropriate pharmacological management and supporting self-management. These management strategies are reflected by the American Thoracic Society (ATS), European Respiratory Society (ERS), Global Initiative for Chronic Obstructive Lung Disease (GOLD) and National Institute for Health and Care Excellence (NICE).3,8
Smoking cessation
Tobacco use is a major cause of many of the world’s top killer diseases and is responsible for approximately one in ten adult deaths worldwide.9 These commonly include cardiovascular disease and lung cancer, and it was found in 2014 that 85% of COPD deaths were attributed to smoking.1 It is estimated that tobacco will kill approximately 10 million people worldwide every year by 2020.3 Tobacco smoke causes direct injury to airway epithelial cells, inducing a specific, persistent inflammation, which differs to that seen in asthma.9,10 The effects of smoking lead to mucus hypersecretion, alveoli wall destruction and smooth muscle thickening, which leads to a decline in lung function. Combined mucous hypersecretion, reduced clearance, and impairment of the lung defence mechanisms explain why patients with COPD, even when stable, carry potential respiratory pathogens in significant concentrations, predisposing them to infections and acute exacerbations of COPD.11
Smoking cessation is therefore considered to be the most clinically and cost-effective way to reduce exposure to COPD risk factors.3,9,10 Smokers have an accelerated decline in lung function as each additional exacerbation in a smoker deteriorates the lung function further. Smoking cessation can slow the progressive loss of lung function and is thought to lessen the decline of forced expiratory volume in 1 second (FEV1) by approximately 35ml per year.10 It benefits all smokers, irrespective of the age at which they quit, making smoking cessation a core component of prevention and treatment of COPD.12 It also reduces the number of hospitalisations and improves quality of life and lowers mortality by 18%.10
Pulmonary rehabilitation
Pulmonary rehabilitation is an individually tailored programme that is designed to optimise the patient’s functional status and reduce symptoms of breathlessness. Physical training can help to reduce the muscle de-conditioning that occurs when the activity of a patient becomes restricted by their breathlessness and fatigue.13 It has been shown to improve health-related quality of life, and has a significant impact on hospital readmissions and mortality rates and is now seen as an integral to the life-long management of individuals with symptomatic chronic respiratory illness.14
Following an acute exacerbation, pulmonary rehabilitation aims to prevent further exacerbations and reduce the severity of exacerbations and associated symptoms to restore the pre-exacerbation functional status. Clinically meaningful improvements have been shown in health-related quality of life, exercise capacity and dyspnoea; having a positive effect on survival rates. An effective rehabilitation programme should be a minimum of six weeks, during which time the effects of muscle de-conditioning are reversed. However, the longer the programme continues, the more effective the results.13,14
Pneumococcal vaccination and influenza 
The principle identified causes of COPD exacerbations include bacterial and viral infections. Patients who have frequent exacerbations have increased airway bacterial colonisation such as Haemophilus influenzae and Streptococcus pneumoniae. Patients colonised by H.influenzae tend to report more symptoms and increased sputum purulence during an exacerbation that those not colonised, suggesting that the presence of bacterial colonisation may lead to more severe exacerbations. Increased airway inflammation in frequent exacerbations therefore may lead to a faster decline in lung function.15
Vaccination against influenza is a highly cost-effective intervention to reduce the number of COPD exacerbations and consequences reduces the number of hospital admissions. For pneumococcal vaccines in COPD patients over 65 years of age or in patients under 65 years of age with a FEV1 <40% predicted, administration of the pneumococcal vaccination has been shown to reduce the frequency of community-acquired pneumonia and a 70% reduction in the risk of death.3,14,15 It should therefore be recommended that all patients with COPD are offered a pneumococcal vaccination and an annual influenza vaccination.
Pharmacological management
A recent strategy developed by GOLD for the management of COPD categorises patients based on their number of exacerbations and symptoms, to provide a better picture of disease status, as below. Treatment should therefore be tailored to individual’s symptoms and frequency of exacerbations. The Medicines Research Council (MRC) dyspnoea scale and the COPD assessment test (CAT) scores are used to assess physical ability and degree of respiratory control due to COPD.1,3
Pharmacological management for COPD is used to reduce symptoms, reduce the frequency and severity of exacerbations, improve health status and exercise tolerance. This is achieved by modification of the long-term decline in lung function associated with patients with COPD.
Increased breathlessness is a common feature of an exacerbation of COPD and is usually managed by increased doses of short-acting bronchodilators. Short-acting beta-agonists and antimuscarinics act on peripheral airways to reduce air trapping, thereby reducing lung volumes and improving symptoms and exercise capacity. Bronchodilators improve the FEV1 by altering airway smooth muscle tone and aid in the widening of the airways and there is some evidence to suggest that it can reduce exacerbation rates.16
Long-acting bronchodilators (both beta-agonists and antimuscarinics) are convenient and more effective at maintaining symptom relief. They reduce exacerbations, hospital admissions, improve symptoms and lung function and health-related quality of life. The effects of long-acting inhaled antimuscarinic therapy reduce the risk of COPD exacerbations by 20–25%.3,16
In accordance with national and international guidance, inhaled corticosteroids in combination with long-acting beta-agonists (ICS/LABA) are indicated in patients with severe to very severe COPD or in milder patients who experience frequent exacerbations or breathlessness.1,3
Regular combination therapy of ICS/LABA has been shown to result in a 25% reduction in the number of exacerbations per patient per annum when compared with monotherapy and placebo.16 Furthermore, the greatest effects were seen in patients with a FEV1 <50% predicted compared to those with moderate degrees of airflow limitation.16 As such, ICS/LABA combinations have a greater protective effect with regard to exacerbation prevention than either class used in isolation and should be reserved for patients who frequently exacerbate.3,16 Inhaled corticosteroids should not be used in isolation without long-acting beta-agonists as this has not been shown to be beneficial in COPD and is unlicenced.
Self-management and rescue medication
The goals of treatment for COPD1,3 are:
  • Reduction of symptoms
– Relieve symptoms
– Improve exercise tolerance
– Improve health status
  • Reduction of risk
– Prevent disease progression
– Prevent and treat exacerbations
– Reduce mortality
Central components of reducing risk involve supporting patients to self-manage and respond to their symptoms promptly. National and international guidance advocates the use of self-management education in conjunction with rescue medicines of oral corticosteroids and antibiotics in response to moderate to severe exacerbations.1,3
This approach has been associated with shorter recovery time, improved lung function, decreased length of inpatient stay and reduced risk of early relapse and treatment failure. As such, patients who have either had, or are at risk of having, a COPD exacerbation should be given self-management advice and rescue medicines.1,3 The Outcomes Strategy for COPD echoes this advice by recommending that self-management education should be provided, with an action plan for worsening symptoms or exacerbations, combined with appropriate rescue medication.17
The main aim of self-management is to prevent exacerbations by empowering patients to develop the required skills and knowledge to identify and treat their exacerbations at an early stage. Guidance suggests that, unless contraindicated, patients who experience such symptoms should promptly:
  • start oral corticosteroid therapy if their increased breathlessness interferes with activities of daily living.
  • start antibiotic therapy if their sputum is purulent.
  • adjust their bronchodilator therapy to control their symptoms.
Table 3 shows that in a real-life setting, the use of self-management plans and rescue medicine in 457 COPD patients had significant reductions in both 30-day readmission and 90-day readmission.18
COPD continues to be a public health burden, resulting in significant morbidity, mortality and increased costs to the healthcare economy. Flare-ups, or exacerbations, associated with COPD are a major cause of morbidity and account for significant costs in its overall management. Various strategies, such as supporting self-management and pulmonary rehabilitation, can significantly reduce the risks of developing flare-ups in COPD. At a time when healthcare resources are stretched, pharmacists are in a pivotal position to ensure that patients with COPD are supported in successfully employing these strategies.
Key points
  • COPD exacerbations are defined as a worsening of baseline symptoms which may include increased breathlessness, sputum production and cough.
  • Exacerbations result in a decline in lung function, reduced quality of life and increases mortality.
  • Utilisation of healthcare resources, increases the costs associated with treating COPD exacerbations as the disease progresses.
  • Several strategies can be used to reduce the risk of exacerbations, including; smoking cessation, pulmonary rehabilitation, pharmacological management and supporting patients to self-manage.
  • Pharmacists have a crucial role in supporting patients to have better control of their COPD, reduce the risk of exacerbations and optimise self-management.
  1. National Institute for Health and Care Excellence. CG101. Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update).
  2. Ferrer M et al. Chronic obstructive pulmonary disease stage and health-related quality of life. Ann Intern Med 1997;127:1072–9.
  3. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of COPD, 2011.
  4. Osman LM et al. Quality of life and hospital readmission in patients with chronic obstructive pulmonary disease. Thorax 1997;52:67–71.
  5. Gadoury MA et al. Self management reduces both short- and long-term hospitalisation in COPD. Eur Respir J 2005;26:853–7.
  6. Anzueto A. Impact of exacerbations on COPD. Eur Respir Rev 2010;19(116):113–18.
  7. Rodriguez-Roisin. COPD exacerbations. 5: Management. Thorax 2006;61(6)525–44.
  8. World Health Organization. (accessed 10 April 2015).
  9. Bartal M. COPD and tobacco smoke. Monaldi Arch Chest Dis 2005;63(4):213–25.
  10. Decramer M et al. COPD. Lancet 2012;379(9832):1341–51.
  11. Pride NB. Smoking cessation: effects on symptoms, spirometry and future trends in COPD. Thorax 2001;56(Suppl II):ii7–ii10.
  12. Rigotti A. Smoking cessation in patients with respiratory disease: existing treatments and future directions. Lancet Respir Med 2013 May;1(3):241–50.
  13. Reardon J et al. Pulmonary rehabilitation for COPD. Respir Med 2005;99 (Supp 2):S19–S27.
  14. Spruit MA et al. An official American Thoracic Society/European Respiratory Society Statement: Key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013;188:e13–e64.
  15. Burge S, Wedzicha JA. COPD exacerbations: definitions and classifications. Eur Respir J 2003;21:(Suppl 41):46s–53s.
  16. Decramer M et al. Targeting the COPD exacerbation. Respir Med 2008;102(Suppl 1):S3-15
  17. Department of Health. The Outcomes Strategy for Chronic Obstructive Pulmonary Disease (COPD) and Asthma in England. Department of Health, 2011.
  18. Dhruve H, Hodson M, Khachi H. COPD exacerbations – is self-management a treatment option. Pharm Manag 2010;29(4):15–21.

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