Exacerbations occur commonly in patients with moderate or severe chronic obstructive pulmonary disease (COPD) but factors affecting their severity and frequency or effects on quality of life are unknown. We measured daily peak expiratory flow rate (PEFR) and daily respiratory symptoms for 1 yr in 70 COPD patients (52 male, 18 female, mean age [+/- SD] 67.5 +/- 8.3 yr, FEV1 1.06 +/- 0.45 L, FVC 2.48 +/- 0.82 L, FEV1/FVC 44 +/- 15%, FEV1 reversibility 6.7 +/- 9.1%, PaO2 8.8 +/- 1.1 kPa). Quality of life was measured by the St. George's Respiratory Questionnaire (SGRQ). Exacerbations (E) were assessed at acute visit (reported exacerbation) or from diary card data each month (unreported exacerbation). In 61 (87%) patients there were 190 exacerbations (median 3; range, 1 to 8) of which 93 (51%) were reported. There were no differences in major symptoms (increase in dyspnea, sputum volume, or purulence) or physiological parameters between reported and unreported exacerbations. At exacerbation, median peak flow fell by an average of 6.6 L/min (p = 0.0003). Using the median number of exacerbations as the cutoff point, patients were classified as infrequent exacerbators (E = 0 to 2) or frequent exacerbators (E = 3 to 8). The SGRQ Total and component scores were significantly worse in the group that had frequent exacerbations: SGRQ Total score (mean difference = 14.8, p < 0.001), Symptoms (23.1, p < 0.001), Activities (12.2, p = 0.003), Impacts (13.9, p = 0.002). However there was no difference between frequent and infrequent exacerbators in the fall in peak flow at exacerbation. Factors predictive of frequent exacerbations were daily cough (p = 0.018), daily wheeze (p = 0.011), and daily cough and sputum (p = 0.009) and frequent exacerbations in the previous year (p = 0.001). These findings suggest that patient quality of life is related to COPD exacerbation frequency.

Although exacerbations of chronic obstructive pulmonary disease (COPD) are associated with symptomatic and physiological deterioration, little is known of the time course and duration of these changes. We have studied symptoms and lung function changes associated with COPD exacerbations to determine factors affecting recovery from exacerbation. A cohort of 101 patients with moderate to severe COPD (mean FEV(1) 41.9% predicted) were studied over a period of 2.5 yr and regularly followed when stable and during 504 exacerbations. Patients recorded daily morning peak expiratory flow rate (PEFR) and changes in respiratory symptoms on diary cards. A subgroup of 34 patients also recorded daily spirometry. Exacerbations were defined by major symptoms (increased dyspnea, increased sputum purulence, increased sputum volume) and minor symptoms. Before onset of exacerbation there was deterioration in the symptoms of dyspnea, sore throat, cough, and symptoms of a common cold (all p < 0.05), but not lung function. Larger falls in PEFR were associated with symptoms of increased dyspnea (p = 0.014), colds (p = 0.047), or increased wheeze (p = 0.009) at exacerbation. Median recovery times were 6 (interquartile range [IQR] 1 to 14) d for PEFR and 7 (IQR 4 to 14) d for daily total symptom score. Recovery of PEFR to baseline values was complete in only 75.2% of exacerbations at 35 d, whereas in 7.1% of exacerbations at 91 d PEFR recovery had not occurred. In the 404 exacerbations where recovery of PEFR to baseline values was complete at 91 d, increased dyspnea and colds at onset of exacerbation were associated with prolonged recovery times (p < 0.001 in both cases). Symptom changes during exacerbation do not closely reflect those of lung function, but their increase may predict exacerbation, with dyspnea or colds characterizing the more severe. Recovery is incomplete in a significant proportion of COPD exacerbations.

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.

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.