In the United States, this means that any tool used in adrug registration trial to evaluate the effect of treatment on frequency, severity, and/orduration of exacerbations must meet the criteria set forth in the Food and Drug Adminis-tration (FDA) draft guidance on patient-reported outcomes

Diary Cards.

Admission to hospital is directly related both to the underlying health of the patient and tohealth policy or coverage within a given country or region. Patients undergoing treatment inregions with relatively liberal admission policies will have more frequent and more“serious” exacerbations, while those in regions with conservative admission policies willhave less frequent and/or fewer “serious” episodes. This bias has serious implications forprevalence estimates in epidemiologic studies, effect estimates in studies examining thelink between exacerbations and disease trajectory, and site selection and treatment out-comes in clinical trials.

There are a number of relatively serious limitations associated with an event-baseddefinition of exacerbation. First, the initial clinic contact and visit is initiated by the patienton the basis of his or her assessment of the episode. With as many as 50% of exacerbationsunreported (8,9), event-based definitions seriously underestimate exacerbation frequency.

The definition proposed by the 1999 Aspen Lung Conference that refers to asustained worsening of the patient’s condition, implying an event that lasts at least 24 hours (2)while worsening beyond normal day-to-day variations, seeks to differentiate the severity ofexacerbations from “bad days” or acute, short-term episodes of cough, breathlessness, or othermanifestations within a given day. This group also proposed that mild exacerbations arecharacterized by an increased need for medication (which patients manage themselves),moderate are those for which the patients seek medical assistance, and severe are those in whichthe patient or caregiver recognizes clear and/or rapid deterioration and requires hospitalization.

In the case of exacerbations of COPD, which are patient-reported events,instruments to detect exacerbations should be based on the conceptual definition and patientdescriptions and experiences of these events and show evidence of reliability, validity, andresponsiveness

(i) understanding the etiology andmechanisms of exacerbations, (ii) determining the impact of exacerbations on the course ofCOPD, and (iii) determining if interventions alter the incidence or the clinical course ofexacerbations.

It is important to realize the difference between the definition of a disease and itsdiagnostic criteria (1). The defining characteristics of a disease are the commonproperties specifying the group of abnormal persons on whom the description of thedisease is based. The definition of a disease is important in communication.Diagnostic criteria are features of the disease chosen from its description thatare found by empirical research to best distinguish the disease from others whichresemble it. The diagnostic criteria may or may not include features of the definingcharacteristics and frequently include features that do not appear in the definition (1).

Recent observations have clearly shown that therapeutic interventionscan, to some extent, prevent exacerbations as well as modify their course. This has created boththe opportunity and the imperative to develop more effective interventions to mitigate theburden of acute exacerbations, which, in turn, has created a need for precise and opera-tionally tractable definitions.

In a multinational cross-sectional interview-based qualitative study by Kessler et al.of 125 patients with moderate to severe COPD, the most common terms patients used whenreferring to a worsening of their condition were “chest infection” (16%; n ¼ 20), “crisis”(16%; n ¼ 20), or an “attack” (6.4%; n ¼ 8) (13). Only two patients understood what theterm “exacerbation” meant.