Elsevier

Clinics in Chest Medicine

Volume 28, Issue 3, September 2007, Pages 525-536
Clinics in Chest Medicine

The Biology of a Chronic Obstructive Pulmonary Disease Exacerbation

https://doi.org/10.1016/j.ccm.2007.05.003Get rights and content

Much of the morbidity and mortality in chronic obstructive pulmonary disease relates to symptomatic deteriorations in respiratory health termed exacerbations. Exacerbations also are associated with changes in lung function and both airway and systemic inflammation. The most common causes of exacerbation are micro-organisms: respiratory viruses such as rhinovirus, and various bacterial species. This article reviews and discusses current understanding of the biology of exacerbations, considering the definition, epidemiology, etiology, and the nature and evolution of the changes in symptoms, lung function, and inflammation that characterize these important events.

Section snippets

What is an exacerbation?

The 2006 update to the World Health Organization (WHO)/US National Heart Lung and Blood Institute (NHLBI) Global initiative for chronic Obstructive Lung Disease (GOLD) document [1] included a definition of exacerbation for the first time. An exacerbation is defined as

“an event in the natural course of the disease characterized by a change in the patient's baseline dyspnoea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular

Epidemiology of exacerbations in chronic obstructive pulmonary disease

COPD is a major global health problem, and one of the few diseases in which mortality rates continue to rise. This reflects an aging population and the relative greater effectiveness of therapies available for other common conditions such as cardiovascular disease and many cancers. Consequently, COPD is projected to be the third leading cause of death in the world by 2020 [9]. While many of these deaths are caused by exacerbations, especially in those with more severe underlying COPD,

Symptomatology: symptom changes during exacerbations of chronic obstructive pulmonary disease

The symptom changes and the timing of such changes that occur during exacerbation have been studied using diary card methodology in which patients are asked to record increases in symptoms above their usual daily severity. This approach has allowed practitioners to develop an understanding not only of the changes present at exacerbation onset, but also how symptoms develop in the prodromal period, and how symptoms resolve in response to therapy.

Seemungal and colleagues [17] studied 504

Assessing exacerbation severity

In the study by Seemungal and colleagues [17], just under half of exacerbations were reported directly to the clinical team, and the greater the number of increased symptoms present at exacerbation onset, the longer it took for these symptoms to return to baseline. Assessing either the magnitude or duration of changes in exacerbation symptoms therefore provides an assessment of exacerbation severity. The same is true for the changes in lung function outlined in the following section. Both

Physiology: lung function changes during exacerbations of chronic obstructive pulmonary disease

The relationships between symptoms and indices of lung function in COPD are complex, but it would be reasonable to assume that the increased symptoms present at exacerbation may be associated with evidence of additional impairment in pulmonary function, and this is indeed the case [23]. Complicating the assessment of changes in lung function is the fact that exacerbations of COPD are extremely heterogenous events, ranging from no more than a transient worsening of symptoms in patients who have

Inflammatory changes during exacerbations of chronic obstructive pulmonary disease

It is now well-established, indeed a defining characteristic [1], that COPD is associated with airway inflammation [36], and numerous individual studies (recently summarized in a meta-analysis) have demonstrated the presence of systemic inflammation in stable COPD [37]. Although highly variable, there is abundant evidence that exacerbations also are associated with increases in both pan-airway and systemic inflammatory markers [38]. The precise origins of systemic inflammation in COPD remain

Etiology: causes of exacerbation in chronic obstructive pulmonary disease

The previous discussion, describing the biology of a COPD exacerbation, is summarized in Fig. 8, which also illustrates that the causes of exacerbation are those insults that either increase airway inflammation or directly affect expiratory flow limitation.

Most literature focuses on micro-organisms as the causes of exacerbations. With molecular biological techniques, it is now possible to identify micro-organisms from airway secretions in most exacerbations, but there are numerous features of

Summary

Exacerbations are important events in the natural history of COPD and a tremendous burden both to the patient and to health care services. Exacerbations are associated with (and currently defined by) changes in symptoms, but there are characteristic underlying and demonstrable alterations in lung function parameters and both airway and systemic inflammation. Most exacerbations are caused by airway infection, and it is perhaps only by understanding the mechanisms of exacerbation that one may

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