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COPD Exacerbations
Causes, Prevention, and Treatment
Alex J. Mackay,
KEYWORDS  Chronic obstructive pulmonary disease  Exacerbation  Respiratory viruses  Bacteria KEY POINTS
 Respiratory viruses (in particular rhinovirus) and bacteria both play a major role in the etiology of exacerbate COPD.  A distinct group of patients appears susceptible to frequent exacerbations, irrespective ofdisease severity and this phenotype is stable over time.  Many current therapeutic strategies help reduce exacerbation frequency.
MBBS, BSc (Hons), MRCP*,

John R. Hurst,

PhD, FRCP

Chronic obstructive pulmonary disease (COPD) is associated with episodes of acute deterioration in respiratory health termed “exacerbations.” Exacerbations are characterized by a worsening of symptoms from theusual stable state, especially dyspnea, increased sputum volume, and purulence. When diagnosing COPD exacerbations, clinicians must also exclude other causes for respiratory deterioration, such as pneumothoraces, pulmonary emboli, and pneumonia, using clinical examination and appropriate investigations if required. Exacerbations are among the most common causes of emergency medical hospitaladmission in the United Kingdom1 (and elsewhere) and the rate at which they occur seems to reflect an independent susceptibility phenotype.2 Exacerbations are important events in the natural history of COPD that help drive lung function decline,3,4 increase the risk of cardiovascular events,5 and are responsible for much of the morbidity6 and mortality7 associated with this highly prevalent condition.FREQUENT EXACERBATOR PHENOTYPE

Patients with a history of frequent exacerbations exhibit faster decline in lung function,3 have worse quality of life,6 have increased risk of hospitalization,8 and have greater mortality (Fig. 1).7 Therefore, it is important to identify patients at risk of
Financial Disclosures: Dr Hurst has received support to attend meetings or speaker and advisory fees fromAstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Pfizer. Academic Unit of Respiratory Medicine, Royal Free Campus, UCL Medical School, Rowland Hill Street, London NW3 2PF, UK * Corresponding author. E-mail address: alexander.mackay@ucl.ac.uk Med Clin N Am 96 (2012) 789–809 doi:10.1016/j.mcna.2012.02.008 medical.theclinics.com 0025-7125/12/$ – see front matter Ó 2012 ElsevierInc. All rights reserved.

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Mackay & Hurst

Fig. 1. Effect of COPD exacerbations in the group with frequent exacerbations. (From Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet 2007;370(9589):786–96; with permission.)

frequent exacerbations. Exacerbations become more frequent and severe as COPD severity increases.9 However, a distinct group ofpatients seems to be susceptible to exacerbations, irrespective of disease severity, and the major determinant of exacerbation frequency is a history of prior exacerbations.2 This phenotype of susceptibility to exacerbations is stable over time and is seen across all severity of airflow obstruction,2 suggesting that patients with the frequent exacerbator phenotype are prone to exacerbations as aresult of intrinsic susceptibility, and develop exacerbations when exposed to particular triggers, such as respiratory infections. Exacerbations are associated with increased systemic and airway inflammation and may be triggered by bacterial and respiratory viral infections. They may also be precipitated by environmental factors (Fig. 2).
VIRAL INFECTIONS Rhinovirus

Rhinovirus is responsiblefor the common cold and initial evidence that respiratory viral infections were important triggers of COPD exacerbations came from the association of coryzal symptoms with exacerbations. Seemungal and colleagues10 found that up to 64% of exacerbations were associated with a symptomatic cold occurring up to 18 days before exacerbation onset. Additionally, exacerbations associated with dyspnea and...