Defining exacerbations in chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease is a very common disease often punctuated by intermittent episodes of exacerbation. These exacerbations affect the natural history of the disease, accelerating a decline in lung function. They affect the individual in many ways and affect the health service caring for these patients. The definition of exacerbation varies and lacks clarity. The definitions used most are either symptom based, for example, breathlessness, sputum production and sputum purulence, or event driven, for example, an event causing a patient to seek healthcare input or change to medications. In this article, we discuss the importance of exacerbations, the clinical definitions, clinical trial definitions, physiological and biomarker evidence of exacerbations and the challenges associated with each of these. Application of a practical definition would aid in our clinical management of patients with chronic obstructive pulmonary disease and facilitate developments in future therapeutic advances through clinical trials.

Keywords:

• biomarkers
• COPD
• definition
• exacerbations

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• There is lack of consensus with regard to the definition of exacerbation in COPD. Exacerbations of COPD are associated with significant morbidity, mortality, and economic and social burden.

• The much used, Anthonisen definition was developed for a study investigating antibiotic use in exacerbations of COPD and is based on the presence of one or more of three cardinal symptoms; including an increase or new onset of breathlessness, sputum production and sputum purulence. Although simple and clinically useful, it is not an objective measurement and has not undergone any validation.

• The GOLD guidelines define an exacerbation as ‘an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication’. This is an example of a health care utilization or event based definition.

• Defining exacerbations is important not only in clinical practice but also in research. The decision on which definition to apply can have an impact on the outcome of clinical trials. A full statement of methods in advance of study commencement is imperative and should include the intended definition of exacerbation. Collecting information can depend on patient diaries, questionnaires or automated telephone calls.

• Biomarkers from pulmonary and systemic sources have been studied and to date there is no perfect biomarker to aid in the definition of COPD. The most studied biomarker is C-reactive protein (CRP), a non-specific marker of inflammation, which still minimally impacts on the clinical definitions.