Patients with chronic obstructive pulmonary disease (COPD) can have acute episodes of worsening symptoms, known generically as exacerbations, which are clinically relevant because they involve an acute deterioration of the patient's health status, worsen the patient's prognosis, and are the main cause of economic expenditure associated with COPD. 1 Seemungal TAR Donaldson GC Paul EA Bestall JC Jeffries DJ Wedzicha JA Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998; 157: 1418-1422 Crossref PubMed Scopus (1786) Google Scholar , 2 Wilkinson TMA Patel IS Wilks M Donaldson GC Wedzicha JA Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003; 167: 1090-1095 Crossref PubMed Scopus (303) Google Scholar , 3 Dransfield MT Kunisaki KM Strand MJ et al. Acute exacerbations and lung function loss in smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017; 195: 324-330 Crossref PubMed Scopus (170) Google Scholar , 4 Soler-Cataluña JJ Martínez-García MA Román Sánchez P Salcedo E Navarro M Ochando R Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005; 60: 925-931 Crossref PubMed Scopus (1401) Google Scholar , 5 Iheanacho I Zhang S King D Rizzo M Ismaila AS Economic burden of chronic obstructive pulmonary disease (COPD): a systematic literature review. Int J Chron Obstruct Pulmon Dis. 2020; 15: 439-460 Crossref PubMed Scopus (93) Google Scholar However, whether these episodes are truly due to an exacerbation of the underlying disease or correspond to worsening symptoms due to any of the diseases that commonly coexist with COPD is difficult to ascertain. In fact, both possibilities can occur separately or in combination. In this context, it is worth noting that effective management of COPD reduces the incidence of exacerbations by around 25–30%, but that most episodes remain (70–75%). 6 Lipson DA Barnhart F Brealey N et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018; 378: 1671-1680 Crossref PubMed Scopus (622) Google Scholar To what extent are these remaining exacerbations due to other factors (ie, are patients misdiagnosed) or mechanisms of COPD not targeted by current preventive treatments? Addressing this question in future research is important to reduce or prevent the incidence and consequences of these exacerbations.