Predictors of Chronic Obstructive Pulmonary Disease Exacerbations

Takeo Ishii; Kozui Kida


Curr Opin Pulm Med. 2014;20(2):138-145. 

In This Article

The State of Current Research Regarding Exacerbations: Factors Observed in Clinical Settings

The frequent-exacerbation phenotype was reported to be associated with an elevated white-cell count, prior exacerbations, a history of gastroesophageal reflux, and severity of airway obstruction.[7]

Regarding inflammatory biomarkers, a study involving a larger population showed that simultaneous elevation of C-reactive protein level, fibrinogen level, and leukocyte count were associated with an increased exacerbation risk.[12] It was also found that higher baseline levels of E-selectin-positive endothelial microparticle (EMP), which is not only a marker of endothelial dysfunction but also considered to have a role in inflammation,[13] may indicate which COPD patients are susceptible to an exacerbation.[14] As EMPs are elevated in COPD and are positively related to the severity of emphysema, EMPs could be a biomarker of COPD itself and the frequent-exacerbation phenotype.[15]

Various clinical components other than the pulmonary function test, which assesses COPD severity, could affect exacerbation susceptibility. A greater degree of lung emphysema and an increased airway wall thickness were associated with COPD exacerbations.[16] Regarding exercise capacity, a lower daily step count and shorter distance in the 6-min walk test predicted future exacerbations and COPD-related hospitalizations.[17] Baseline scores on the COPD Assessment Test (CAT), an eight-item questionnaire designed to assess and quantify the impact of COPD symptoms on health status, are also elevated in frequent exacerbators.[18]

The assessment of prior exacerbations is useful for predicting a frequent-exacerbation phenotype. As mentioned above, a new GOLD classification system,[1] which assesses COPD exacerbation history, better predicted future exacerbations,[2,3] and the occurrence of every new severe exacerbation requiring hospitalization worsened the disease course and increased the risk of a subsequent exacerbation.[19] We also found that among the three multidimensional assessment systems [Body Mass Index, Obstruction, Dyspnea, Exercise (BODE); Dyspnea, Obstruction, Smoking, Exacerbation (DOSE); and Age, Dyspnea, Obstruction (ADO) indices], the DOSE index, in which prior exacerbations are taken into account, was a better predictor of COPD exacerbations.[20]

It was also reported that this frequent-exacerbation phenotype is associated with comorbidities including not only gastroesophageal reflux, but also depression,[21] cognitive dysfunction,[22] and pulmonary arterial enlargement.[23]