The phenotypes of acute exacerbations of COPD
Presented by Prof Maarten van den Berge, Netherlands
SUMMARY
There are different exacerbation subtypes within COPD. Recognition of the exacerbation subtype is important as it may have an impact on treatment decisions. Comorbidity and severity of disease must also be considered. It is not always easy to accurately diagnose an exacerbation or to objectively grade its severity.
What are exacerbations?
Exacerbation is considered as an acute worsening of the patient’s usual pattern of respiratory symptoms beyond normal day-to-day variability. These include increased dyspnoea, worsening of cough, increased sputum volume and sputum purulence. Thinking about severity, a moderate exacerbation is usually treated with prednisolone and/or antibiotics and severe cases need hospitalization and may lead to death.
Triggers of exacerbation
Of the different subtypes of exacerbations, viruses is the most important factor, but due to limited testing, there is limited data of its role. Triggers may also be bacteria, eosinophilic type 2-inflammation and other factors.
Exacerbations are not unannounced
The term acute exacerbation is misleading, says prof. van der Berge, as it has been shown that the worsening of the symptoms starts already seven days before the actual event1. This timepoint could be an excellent opportunity to intervene particularly in the case when the subtype of the exacerbation is known. For example, patients with higher eosinophilic count have a higher risk for exacerbations2,3. In these cases, treating the patient with corticosteroid containing inhalation therapy could help avoid escalation. Eosinophils are increased during exacerbations in a certain subset of patients, not in all4.
Systemic corticosteroids and antibiotics in treating COPD exacerbations
Comparing outcomes for patients suffering from exacerbation, where standard of care (all receive prednisolone and antibiotics) with biomarker-based treatment, study results support the latter. Results from the original study5 by the OXFORD-group, published in 2012, was confirmed in 20246. In the biomarker arm, patients received antibiotics plus either prednisolone or placebo. Lung function, health status and symptoms were similar in both groups. However, symptom recovery was slower in the patients who received prednisolone if their eosinophilic count was low. The conclusion was that prednisolone should only be given to the right phenotypes of exacerbations to avoid harming the patients. If the patient already has taken prednisolone, this will impact biomarker count, and this should be checked.
Antibiotics or not?
An old (but landmark) study published in 1987 showed that exacerbating patients treated by antibiotics vs. placebo had a better outcome7. The same study identified three exacerbation subtypes:
- Increased dyspnea, sputum volume and sputum purulence
- Two of three above mentioned symptoms present
- One of the above symptoms present AND upper respiratory infection, fever, increased wheeze or cough or increased respiratory or heart rate
Antibiotics were beneficial only in the first subtype exacerbations.
Exacerbation severity
Exacerbation severity is divided in three categories:
Mild: events that result in change of COPD medications for>2 days.
Moderate: Events requiring treatment with antibiotics and/or systemic corticosteroids
Severe: Events that result in hospitalization or ER visit8.
Severity of COPD exacerbations: The Rome proposal
The severity of an exacerbation relies exclusively on a patient’s perception of increased respiratory symptoms and physician’s perception regarding the treatment options, both subjective. The symptoms can be mimicked by other clinical conditions. Lack of measurable pathophysiological variables is another challenge. Published in 2021, the Rome proposal suggests a new approach of diagnosing COPD exacerbations and their severity. The assessment should include ruling out other clinical causes of symptoms (e.g. heart failure, pneumonia or pulmonary embolism9).
Post-exacerbation vulnerability
Risk of coronary symptoms of heart failure increases during and shortly after an COPD exacerbation. The risk of acute coronary syndrome increases almost 10-fold, and the risk of heart failure increases 27-fold during the first seven days. It is not fully understood what the causes behind these increases are10.
The bottom line
Understanding and recognizing the exacerbation subtype is important as it provides guidance for treatment decisions.
Pekka Ojasalo
Medical Advisor
References
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ID 8699-18.06.2024