Limits...
Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease.

Wedzicha JA, Brill SE, Allinson JP, Donaldson GC - BMC Med (2013)

Bottom Line: This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Respiratory Medicine, Royal Free Campus, University College London, Rowland Hill Street, Hampstead, London NW3 2PF, UK. w.wedzicha@ucl.ac.uk

ABSTRACT
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the 'frequent exacerbator' phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

Show MeSH

Related in: MedlinePlus

Annual rate of myocardial infarction against the annual rate of exacerbation (defined as prescription of steroids and antibiotics together). Reproduced from Donaldson et al. [86] with permission.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3750926&req=5

Figure 3: Annual rate of myocardial infarction against the annual rate of exacerbation (defined as prescription of steroids and antibiotics together). Reproduced from Donaldson et al. [86] with permission.

Mentions: Exacerbations have a profound and direct impact on patients’ cardiovascular status. Of 242 patients hospitalized for COPD exacerbation in Scotland, 12% were found to meet universally agreed criteria for the diagnosis of myocardial infarction with raised troponin and either chest pain or serial electrocardiogram (ECG) changes [84]. The period following an exacerbation appears to be particularly high risk. In the 4-year UPLIFT trial, the relative risks of cardiac failure, myocardial infarction and stroke were 10.71, 3.20 and 2.31 respectively, in 2,289 patients, for the 180 days after their first exacerbation compared to the 180 days preceding it [85]. In addition, evidence from a large observational database in the UK showed a 2.27-fold increased risk of clinical myocardial infarction in the first 5 days after an exacerbation and a 1.26-fold increased risk of stroke in the first 49 days afterwards [86]; patients who experienced myocardial infarction or stroke had a higher yearly exacerbation frequency than those who did not (Figure 3). Pulmonary embolism may be also associated with COPD exacerbations, though the reported prevalence of pulmonary embolism is variable [87]. However, patients with exacerbations complicated by pulmonary embolism have a poorer outcome [79].


Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease.

Wedzicha JA, Brill SE, Allinson JP, Donaldson GC - BMC Med (2013)

Annual rate of myocardial infarction against the annual rate of exacerbation (defined as prescription of steroids and antibiotics together). Reproduced from Donaldson et al. [86] with permission.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3750926&req=5

Figure 3: Annual rate of myocardial infarction against the annual rate of exacerbation (defined as prescription of steroids and antibiotics together). Reproduced from Donaldson et al. [86] with permission.
Mentions: Exacerbations have a profound and direct impact on patients’ cardiovascular status. Of 242 patients hospitalized for COPD exacerbation in Scotland, 12% were found to meet universally agreed criteria for the diagnosis of myocardial infarction with raised troponin and either chest pain or serial electrocardiogram (ECG) changes [84]. The period following an exacerbation appears to be particularly high risk. In the 4-year UPLIFT trial, the relative risks of cardiac failure, myocardial infarction and stroke were 10.71, 3.20 and 2.31 respectively, in 2,289 patients, for the 180 days after their first exacerbation compared to the 180 days preceding it [85]. In addition, evidence from a large observational database in the UK showed a 2.27-fold increased risk of clinical myocardial infarction in the first 5 days after an exacerbation and a 1.26-fold increased risk of stroke in the first 49 days afterwards [86]; patients who experienced myocardial infarction or stroke had a higher yearly exacerbation frequency than those who did not (Figure 3). Pulmonary embolism may be also associated with COPD exacerbations, though the reported prevalence of pulmonary embolism is variable [87]. However, patients with exacerbations complicated by pulmonary embolism have a poorer outcome [79].

Bottom Line: This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Respiratory Medicine, Royal Free Campus, University College London, Rowland Hill Street, Hampstead, London NW3 2PF, UK. w.wedzicha@ucl.ac.uk

ABSTRACT
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the 'frequent exacerbator' phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

Show MeSH
Related in: MedlinePlus