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COPD is a heterogeneous condition. This concept has evolved from classic descriptions of pink puffers and blue bloaters to a more complex understanding of disease phenotypes. Phenotypes are relevant because they may predict an important clinical outcome or a specific underlying disease mechanism (endotype), either or both of which might suggest benefit from a particular intervention—‘personalised medicine’. In addition to the progressive decline in lung function, symptoms and physical performance that characterise COPD, (some) patients are prone to periodic deteriorations in respiratory health called exacerbations. And given that exacerbations are responsible for much of the morbidity, mortality and therefore healthcare costs associated with COPD, exacerbation-susceptible patients or ‘frequent exacerbators’ form a clinically relevant phenotype. Why does one patient get more exacerbations than another? A simple clinical question, without a simple answer.
To this first level of complexity in COPD—phenotypes—we must add that exacerbations themselves are heterogeneous events. Assume, for a moment, that a patient is truly having an exacerbation (and not one of the other pathologies that can cause symptom deterioration in COPD1). That exacerbation might be caused by acquisition of a respiratory virus, …