Chronic obstructive pulmonary disease (COPD) is defined independently of exacerbations, which are largely a feature of moderate-to-severe disease. This article is the result of a workshop that tried to define exacerbations of COPD for use in clinical, pharmacological and epidemiological studies. The conclusions represent the consensus of those present.This review describes definitions, ascertainment, severity assessments, duration and frequency, using varying sources of data including direct patient interview, healthcare databases and symptom diaries kept by patients in studies.The best general definition of a COPD exacerbation is the following: an exacerbation of COPD is a sustained worsening of the patient9s condition, from the stable state and beyond normal day-to-day variations that is acute in onset and may warrant additional treatment in a patient with underlying COPD.A more specific definition for studies where a bacteriological cause of exacerbation is being studied is included, as well as simpler definitions for retrospective identification from database sources. Prospective diary card assessments are best recorded as changes from an agreed baseline, rather than absolute symptom severities. Diary cards identify many unreported exacerbations, which on average have similar severities to reported exacerbations. A scale for exacerbation severity is proposed that incorporates in-and outpatient assessments. Exacerbation duration, which also relates to severity, is defined from diary card reports. Healthcare utilisation is not an adequate substitute for severity, depending on many unrelated social and comorbidity factors. It is an outcome in its own right.

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased airway and systemic inflammation, though relationships between exacerbation recovery, recurrent exacerbation and inflammation have not been previously reported. In the present study, inflammatory changes at COPD exacerbations were related to clinical nonrecovery and recurrent exacerbations within 50 days.Serum interleukin (IL)-6, C-reactive protein (CRP), sputum IL-6 and IL-8 were measured in 73 COPD patients when stable, at exacerbation and at 7, 14 and 35 days post-exacerbation.In 23% of patients, symptoms did not recover to baseline by day 35. These patients had persistently higher levels of serum CRP during the recovery period. A total of 22% of the patients who had recurrent exacerbations within 50 days had significantly higher levels of serum CRP at day 14, compared with those without recurrences: 8.8 mg?L -1 versus 3.4 mg?L -1 . Frequent exacerbators had a smaller reduction in systemic inflammation between exacerbation onset and day 35 compared with infrequent exacerbators. Nonrecovery of symptoms at chronic obstructive pulmonary disease exacerbation is associated with persistently heightened systemic inflammation. The time course of systemic inflammation following exacerbation is different between frequent and infrequent exacerbators. A high serum C-reactive protein concentration 14 days after an index exacerbation may be used as a predictor of recurrent exacerbations within 50 days.KEYWORDS: Chronic obstructive pulmonary disease, exacerbation, inflammation C hronic obstructive pulmonary disease (COPD) is characterised by episodic increases in respiratory symptoms, which are called exacerbations. These episodes contribute considerably to the increased morbidity, mortality and healthcare costs associated with this condition. Some patients are prone to frequent exacerbations and these patients have worse health status [1], greater limitation of their daily activities [2] and faster disease progression [3,4].COPD exacerbations are associated with increases in airway and systemic inflammation [5][6][7][8][9][10][11] that are heterogeneous and probably related to the aetiology of the exacerbation [5,12]. However, no detailed information is available on the time course of airway and systemic inflammation during exacerbations, and how these changes relate to clinical indices of exacerbation severity, including the length of recovery. The current authors have previously shown that patients with frequent exacerbations have increased airway inflammation in the stable state [5]. It has also been demonstrated that nonrecovery of symptoms and peak flow at 35 days after the onset of the exacerbation occurs in f25% of patients [13].Exacerbations have a tendency to cluster in an individual as demonstrated by studies of patients hospitalised with severe COPD exacerbations. Such studies have shown that after the index exacerbation, patients are at increased risk of readmission and one study showed that 34% of patients were r...

Common colds are associated with exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of the common cold virus (human rhinovirus) in the production of symptoms and lower airway inflammation at COPD exacerbation is unknown.Thirty three patients with moderate-to-severe COPD were seen at baseline, when the number of chest infections in the previous year was noted, and acutely at COPD exacerbation. Within 48 h after the onset of the exacerbation and at baseline, nasal aspirates and induced sputum were taken for rhinovirus reverse transcriptase polymerase chain reaction (RT-PCR) analysis and determination of cytokine levels. Symptoms, recorded on diary cards, were noted and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured.At exacerbation, mean FEV1 and FVC fell significantly from baseline (p<0.001). Ten of 43 exacerbations were associated with rhinovirus infection, detected in induced sputum. In four of these, nasophageal samples contained no detectable rhinovirus. All baseline samples were negative for rhinovirus. The simultaneous presence of increased nasal discharge/nasal congestion (in 26 of the 43 exacerbations) and increased sputum (29 exacerbations) was strongly associated with the presence of rhinovirus (odds ratio 6.15; p=0.036). Total symptom scores were greater for rhinovirus as compared to nonrhinovirus exacerbations (p=0.039). Median baseline sputum interleukin-6 levels rose from 90.2 to 140.3 pg . mL -1 at exacerbation (p=0.005); the change was greater in the presence of rhinovirus infection (p=0.008).Rhinovirus infection can be detected at chronic obstructive pulmonary disease exacerbation. This is associated with elevation of lower airway interleukin-6 levels, which may mediate lower airway symptom expression during chronic obstructive pulmonary disease exacerbations. Eur Respir J 2000; 16: 677±683.

Non-invasive ventilation has been used in chronic respiratory failure due to chronic obstructive pulmonary disease (COPD), but the effect of the addition of nasal positive-pressure ventilation to long-term oxygen therapy (LTOT) has not been determined. We report a randomized crossover study of the effect of the combination of nasal pressure support ventilation (NPSV) and domiciliary LTOT as compared with LTOT alone in stable hypercapnic COPD. Fourteen patients were studied, with values (mean +/- SD) of Pao2 of 45.3 +/- 5.7 mm Hg, PaCO2 of 55.8 +/- 3.6 mm Hg, and FEV1 of 0.86 +/- 0.32 L. A 4 wk run-in period (on usual therapy) was followed by consecutive 3-mo periods of: (1) oxygen therapy alone, and (2) oxygen plus NPSV in randomized order. Assessments were made during run-in and at the end of each study period. There were significant improvements in daytime arterial PaO2 and PaCO2, total sleep time, sleep efficiency, and overnight PaCO2 following 3 mo of oxygen plus NPSV as compared with run-in and oxygen alone. Quality of life with oxygen plus NPSV was significantly better than with oxygen alone. The degree of improvement in daytime PaCO2 was correlated with the improvement in mean overnight PaCO2. Nasal positive-pressure ventilation may be a useful addition to LTOT in stable hypercapnic COPD.

Chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations demonstrate increased stable-state airway inflammation. Tiotropium has been shown to reduce exacerbation frequency, but its effect on airway inflammation is unknown. The aim of the present study was to investigate the effect of tiotropium on sputum inflammatory markers and exacerbation frequency.Patients (n5142) were randomised to receive tiotropium or placebo in addition to their usual medication for 1 yr. Sputum and serum cytokines were assayed by ELISA and exacerbation frequency calculated using a symptom-based diary.There was no difference in the area under the curve for sputum interleukin (IL)-6 or myeloperoxidase between the groups, but sputum IL-8 level was increased in the tiotropium arm. There was no difference between start and end of study in serum IL-6 or C-reactive protein level. Tiotropium was associated with a 52% reduction in exacerbation frequency (1.17 versus 2.46 exacerbations?yr -1 ). Of patients on tiotropium, 43% experienced at least one exacerbation, compared with 64% on placebo. The total number of exacerbation days was reduced compared with placebo (17.3 versus 34.5 days). Tiotropium reduces exacerbation frequency in chronic obstructive pulmonary disease, but this effect does not appear to be due to a reduction in airway or systemic inflammation.