COPD exacerbations definition needs bringing up to date: Dr Alvar Agusti


By Tony Kirby

7 Aug 2018

The current definition of COPD exacerbations is too vague and needs to be dragged into the 21st century, international experts say.

Writing in a comment published in Lancet Respiratory Medicine, Dr Alvar Agusti, from the Respiratory Institute, Hospital Clinic, Barcelona, Spain and colleagues say the current definition of COPD exacerbations – an acute event characterised by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication – is vague.

“When this definition is used, exacerbation-like events can be identified even in individuals without COPD,” they write.

Due to differences between patients, the core COPD exacerbation symptom of dyspnoea can manifest differently and lead to an over-reliance on symptoms for diagnosis. Furthermore, exacerbations are heterogenous with four types identified to date – making their prevention and treatment empirical at best.

They propose a new definition of COPD as an acute clinical event characterised by an inflammatory burst (pulmonary, systemic, or both) in response to a number of environmental factors that, in a patient with COPD, leads to increased work of breathing and dyspnoea, with or without cough, sputum production, or purulence.

The inflammatory burst can be confirmed if a C-reactive protein (CRP) level of 3mg/L is recorded, especially in combination with increased dyspnoea, sputum volume or sputum purulence. Increased circulating neutrophils or use of an electronic nose to detect volatile organic compounds can also confirm an inflammatory burst.

Following this, other potential causes of the increased respiratory symptoms need to be ruled out (and treated as necessary), which include conditions such as pneumonia, pneumothorax, pulmonary emboli, myocardial infarction, heart failure and arrhythmia.

To guide precision therapy, the authors say the cause of the exacerbation must be identified.

“Airway infection is the main trigger of COPD exacerbations. Sputum purulence has been a traditional descriptor of the bacterial origin of COPD exacerbations and the need for antibiotic treatment, but clearly lacks specificity. Thus, to confirm the infectious cause of a COPD exacerbation, and to guide precision therapy, improved biomarkers, ideally at the point of care, are require,” they add.

According to Dr Agusti and colleagues, RNA sequencing and quantitative PCR are among the techniques that could be used to more accurately identify the cause of exacerbations, as could the use of an electronic nose originally used to confirm the inflammatory burst. Circulating blood eosinophils are also a good marker for eosinophil-related COPD exacerbations which tend to respond better to systemic glucocorticoid therapy.

However, while this type of diagnostic analysis may be relatively straightforward in a hospital setting (where most serious COPD exacerbations occur), it may be more difficult in primary care.

The authors also conceded that their suggested approach requires validation in large, prospective studies.

In an interview with The Limbic Dr Agusti said he was in the early stages of designing such a study.

“We propose that it is time to move the diagnosis and management of COPD exacerbations into a precision medicine framework,” his article concludes.

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