An Updated Definition and Severity Classification of Chronic Obstructive Pulmonary Disease Exacerbations: The Rome Proposal

Abstract

Over 200 years ago, René Laennec published the first description of emphysema, an important pathobiological element of what is today known as chronic obstructive pulmonary disease (COPD) (1). He stated that the disease was characterized by persistent dyspnea punctuated by acute episodes of worsening, frequently associated with newly developed and/or worsening cough and sputum (labeled as “acute catarrh”) that could lead to “suffocation.” These episodes have subsequently been termed “exacerbations of COPD” (ECOPDs) (2, 3). Over 150 years later, Anthonisen and colleagues (4) provided a definition, similar to Laennec’s, that has remained relatively unchanged over the last 35 years and forms the basis of the European Respiratory Society/American Thoracic Society definition: “In a patient with underlying COPD, exacerbations are episodes of increasing respiratory symptoms, particularly dyspnea, cough and sputum production, and increased sputum purulence” (5). A slightly modified definition has been used primarily in the research field: “A sustained worsening of the patient’s condition from the stable state and beyond normal day-to-day variations, necessitating a change in regular medication in a patient with underlying COPD” (6). This definition is similar to that in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy document, which reads, “An acute worsening of respiratory symptoms that results in additional therapy” (7). GOLD then classifies ECOPD severity as mild when only symptoms are reported and the patient is treated with inhaled short-acting bronchodilators; moderate when the patient receives antibiotics, systemic corticosteroids, or both; and severe when the patient visits an emergency room or is hospitalized because of the event (6, 7). Without denying the therapeutic progress made in the prevention of ECOPDs (5–8), treatment of the episodes per se has remained relatively unchanged (5, 7, 9). The current definition of ECOPD has several shortcomings that adversely affect clinical and healthcare decisions (see Table E1 in the online supplement). First, it relies exclusively on a patient’s subjective perception of increased respiratory symptoms, which varies from patient to patient (10) and can be mimicked and/or aggravated by other conditions such as pneumonia, cardiac events, or pulmonary embolism (6, 7, 11, 12). Second, it does not relate the symptoms to measurable pathophysiological variables that could characterize the event itself. Third, it lacks a framework for timing of the event’s evolution, an element that can help differentiate ECOPDs from other processes with similar symptoms. Finally, severity is established post hoc by the healthcare resource used to treat the event (13, 14), with this subjectivity introducing variability due to differences between practitioners and healthcare systems. A novel approach is therefore needed because precise, practical, and objective point-of-care definitions and severity assessments for acute medical events are needed by clinicians and researchers if they are to effectively diagnose them at the point of contact, assess the prognosis, and implement precision treatment (15). All of these shortcomings could be overcome by integrating knowledge gathered from observational and interventional studies, as well as with the help of currently available technology capable of measuring in real time the clinical and laboratory variables that can serve as surrogate markers of event severity. This perspective proposes an updated definition and severity classification of ECOPDs based on the principles outlined by Scadding (16) for the taxonomy of diseases, integrating symptoms, function, and surrogate markers of the process underlying ECOPDs. It intends to be objective, practical, and useful to clinicians and researchers alike. In its development, the authors acknowledge that episodes of the worsening of respiratory symptoms similar to ECOPDs may occur in patients with chronic diseases other than COPD, and these potential causes should be considered in the differential diagnosis of the event (7, 17). The process itself was initiated and coordinated by B.R.C. and L.M.F., aided by a medical writer (D.Y.), who identified experts with international recognition who have conducted research and published on the definition, diagnosis, pathobiology, and/or treatment of ECOPDs as well as similar events in closely related fields. A modified Delphi method (18, 19) was considered the most appropriate scientific tool to achieve the desired goals because 1) it is a valid method to obtain consensus based on informed opinions; 2) it provides a structured mechanism to maintain a fluid communication process, allowing individuals to deal with a complex problem; 3) the issue in question does not lend itself to precise analytical techniques but can benefit from subjective judgments on a collective basis; and 4) the method is based on anonymous responses to the selected items