Patients at risk of exacerbations

Several studies suggest a link between inflammation and exacerbations. It has been shown that COPD patients with frequent exacerbations have increased airway inflammation in the stable state1 and that during an exacerbation there is an increase in airway inflammation.1,2

Increased inflammatory markers in the stable state and during an exacerbation

One study investigated the sputum cell and cytokine characteristics in stable COPD and during an exacerbation.1 It was found that patients with 3 or more exacerbations per year had higher sputum levels of IL-6 and IL-8 in the stable state than patients with 2 or fewer exacerbations per year. During an exacerbation the IL-6 levels were increased compared with stable condition, while no statistically significant rises could be found for IL-8 levels. The authors conclude that baseline sputum cytokine levels could be used to predict the frequency of future exacerbations.

A significant rise in IL-6 levels during an exacerbation was confirmed in this and other studies.2 Another important finding of the Bhowmik study is that the magnitude of the increase in sputum IL-8 correlated with the exacerbation recovery time.

Chronic cough and sputum indicates increased risk of exacerbations in COPD patients

Studies have shown that COPD patients with chronic cough and sputum production have on average more exacerbations per year compared with COPD patients without these symptoms (Figure 1).3 Frequent exacerbations of two or more per year occurred in 55% of patients with chronic cough and sputum, compared with 22% of patients without chronic cough and sputum.  

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Figure 1: Association of chronic cough and sputum levels to exacerbation rate.3
Adapted from Burgel et al.2009.3

Exacerbations drive disease progression4

The fact that patients with frequent exacerbations have an increased risk of disease progression emphasizes the importance of preventing exacerbations (Figure 2).5

Figure 2: Disease progression associated with frequent exacerbations.5–8

Expert opinion


  1. Bhowmik A, Seemungal TA, Sapsford RJ, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax 2000;55:114-20.
  2. Perera WR, Hurst JR, Wilkinson TM, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation. Eur Respir J 2007;29:527-34.
  3. Burgel PR, Nesme-Meyer P, Chanez P, et al. Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest 2009;135:975-82.
  4. Wedzicha JA & Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet 2007;370:786-96.
  5. Donaldson GC, Seemungal TA, Bhowmik A, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002;57:847-52.
  6. Seemungal TA, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;151:1418-22.
  7. Groenewegen KH, Schols AM & Wouters EF. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD. Chest 2003;124:459-67.
  8. Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925-31.


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