Effect of Exacerbation on Quality of Life in Patients

with Chronic Obstructive Pulmonary Disease

TERENCE A. R. SEEMUNGAL, GAVIN C. DONALDSON, ELIZABETH A. PAUL, JANINE C. BESTALL,
DONALD J. JEFFRIES, and JADWIGA A. WEDZICHA
Academic Departments of Respiratory Medicine, Physiology, Environmental and Preventive Medicine, and Virology,
St. Bartholomews and Royal London School of Medicine and Dentistry, London, United Kingdom

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 [6 SD] 67.5 6 8.3 yr, FEV1 1.06 6 0.45 L, FVC
2.48 6 0.82 L, FEV1/FVC 44 6 15%, FEV1 reversibility 6.7 6 9.1%, PaO2 8.8 6 1.1 kPa). Quality of life
was measured by the St. Georges 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 5 0.0003). Using the median
number of exacerbations as the cutoff point, patients were classified as infrequent exacerbators (E 5
0 to 2) or frequent exacerbators (E 5 3 to 8). The SGRQ Total and component scores were significantly worse in the group that had frequent exacerbations: SGRQ Total score (mean difference 5
14.8, p , 0.001), Symptoms (23.1, p , 0.001), Activities (12.2, p 5 0.003), Impacts (13.9, p 5 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 5 0.018), daily
wheeze (p 5 0.011), and daily cough and sputum (p 5 0.009) and frequent exacerbations in the previous year (p 5 0.001). These findings suggest that patient quality of life is related to COPD exacerbation frequency. 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;157:14181422.

Patients with moderate and severe chronic obstructive pulmonary disease (COPD) are prone to exacerbations; the frequency
of these exacerbations increases with the severity of COPD
(1). However, there is little information on the effect of exacerbation on quality of life. Some patients are prone to frequent exacerbations that may have considerable impact on activities of daily living and well-being, yet factors predicting
development and severity of exacerbation have not been studied. Impairment of quality of life can be quantified with disease-specific quality-of-life measures, validated for use in chronic
respiratory disease (2, 3). Changes in lung function occur with
exacerbation, but these are variable, because of the relatively
fixed airflow obstruction. However, quality-of-life scores show
only a moderate relationship with symptoms and physiological
(Received in original form September 9, 1997 and in revised form December 11,
1997)

parameters (47) and thus exacerbation may produce considerable distress to the patient, without change in lung function.
Previous studies of exacerbations have concentrated on predictive factors for hospital admission in patients with COPD
(811). Poor quality of life is related to likelihood of hospital
admission and to increased use of resources. However, most
COPD exacerbations are treated at home and are not associated with hospital admission. There is no information as to the
impact of such exacerbations and their differing severity on
the daily life of COPD patients.
In this study, patients with moderate to severe COPD were
followed prospectively over 12 mo. Patients recorded daily
symptoms and daily peak flow on diary cards and reported exacerbations to the clinical team. We have investigated the effect of exacerbation frequency and severity on health-related
quality of life and evaluated factors that predispose to exacerbation.

Supported by the British Lung Foundation and the Hedley Foundation.

METHODS

Correspondence and requests for reprints should be addressed to Dr. J. A. Wedzicha, Academic Department of Respiratory Medicine, The London Chest Hospital, Bonner Road, London E2 9JX, UK.

Patients

Am J Respir Crit Care Med Vol 157. pp 14181422, 1998

Eighty-four (57 male, 27 female) of 125 (81 male, 44 female) patients

with COPD who attended the outpatient clinics were recruited in Oc-

1419

Seemungal, Donaldson, Paul, et al.: Effect of Exacerbation on QOL in COPD

tober 1995. Inclusion criteria were: FEV1 , 70% predicted for age
and height, b2-agonist reversibility , 15% or 200 ml (12, 13), and no
exacerbations for the previous 4 wk. Exclusion criteria were asthma,
bronchiectasis, carcinoma of the bronchus, or inability to complete diary cards. During the study period there were three deaths, one from
allergic bronchopulmonary aspergillosis and two from acute exacerbations of COPD. Eleven patients withdrew, 10 because of poor compliance and one because of reactivation of tuberculosis. Thus, the number of patients who remained in the study was 73 (54 male, 19 female)
with 70 patients (52 male, 18 female) completing the study.
At recruitment, measurements were made of FEV1 and FVC (rolling seal spirometer; Sensor Medic Corp., Yorba Linda, CA), reversibility to salbutamol (400 mg by metered-dose inhaler) after withdrawing bronchodilators for 4 h, arterialized ear lobe blood gases (model
278 Blood Gas Analyzer; Ciba-Corning, Medfield, MA) (14), the number of exacerbations during the previous year (past exacerbations), and
the cardiovascular history. Steroid use, vaccine history, and daily symptoms (dyspnea, cough, wheeze, sputum production) were recorded.
Patients completed daily diary cards after morning medication to
record peak expiratory flow rate (PEFR) using a Mini-Wright peak
flow meter (Clement Clarke International Ltd, Harlow, UK), increase
in upper respiratory tract symptoms (nasal discharge, sore throat), and
increase in lower respiratory tract symptoms (dyspnea, sputum, cough,
wheezing) and fever. Patients were reviewed monthly until April 1996
and every three months during the summer months for a total followup of 12 mo. Approval for this study was obtained from the ethics
committee of the East London and City Health Authority.

Exacerbations
An exacerbation was diagnosed (15) if the following symptom patterns were experienced for at least two consecutive days: either two or
more of three major symptoms (increase in dyspnea, sputum purulence, and increased sputum volume); or any one major symptom together with any one of the following minor symptomsincrease in nasal discharge, wheeze, sore throat, cough, or fever. When patients
noticed deterioration in symptoms, they telephoned a member of the
clinical team and were seen within 48 h. If their symptoms were compatible with a reported exacerbation, spirometry was measured and
treatment prescribed of antibiotics and/or oral steroids and/or increased inhaled steroids. Exacerbations identified from the diary
cards at clinic visits when patients were not reviewed acutely were
termed unreported exacerbations.

Health-related Quality Of Life (HRQOL)

Indices of health-related quality of life (HRQOL) were obtained using the St. Georges Respiratory Questionnaire (SGRQ) (2, 16).
Three component indices were calculated using empirically derived
weightings: Symptom, Activity, and Impact scores from which a Total
score was computed. Scores vary from 0 (no disability) to 100 (maximum disability). Patients were also asked to complete the Medical
Research Council (MRC) dyspnea scale questionnaire (17) which
consists of five grades: 1shortness of breath with strenuous exercise;
2shortness of breath when hurrying; 3walking slower than people
of same age; 4needing to stop after walking 100 yards on level; 5
too breathless to leave the house. The questionnaires were completed
by the patients at the last clinic visit without directions from the researchers.

Statistical Analysis
Reported and unreported exacerbations were compared by acute
symptoms (chi-square test) and changes in PEFR at the time of exacerbation (Mann-Whitney U test). The Wilcoxon signed rank test was
used to test significance of PEFR change over the 2 d prior to exacerbation from zero. Baseline PEFR was taken as the mean of Days 14 to
7 prior to onset of exacerbation. Recovery of PEFR was defined as
the time at which the 3-d moving average of PEFR exceeded or was
nearest baseline.
The 14 patients who could not complete the study were compared
with the 70 patients who completed the study on the baseline physiological measures, history of symptoms, and past exacerbations. Continuous variables were compared using t tests and discrete variables
using the chi-squared test. FEV1 and PaCO2 were not normally distrib-

uted and log transformation of these variables was used in all analyses. For each patient the mean fall in PEFR over all exacerbations was
calculated. MRC grade was divided into two groups, grades 2 and 3,
and grades 4 and 5. The median number of exacerbations was 3 per
patient and this was taken as a cutoff point to divide the patients into
two groups: those who had 0, 1, or 2 exacerbations during the year and
those with 3 or more. The relationship between exacerbation group
and individual variables was described using univariate logistic regression. The effect of all variables together on exacerbation group was
then explored using backward logistic regression. The SGRQ was normally distributed and t tests were used to compare group means for dichotomous variables which included exacerbation group, MRC grade,
past exacerbations, sex, and symptoms. Physiological variables were
entered into individual regression equations with SGRQ as the outcome variable and then combined in a backward multiple regression.

RESULTS
Description of the Cohort

Table 1 shows the baseline data on the 73 patients who remained in the study, though all further analysis was carried
out only on the 70 who completed the study. Twenty-seven of
the 70 patients had cardiac failure, 14 had ischemic heart disease, 38 had three or more past exacerbations, and nine were
on long-term oxygen therapy. The median MRC dyspnea
score was 4 (range, 2 to 5). Twenty-two were current smokers,
with a mean of 46 6 35 pack-years for the cohort. Sixty-six patients were receiving inhaled steroids (beclomethasone, budesonide, or fluticasone) using a mean dose of 1.11 6 0.66 mg daily
for 4.78 6 3.75 yr. Ten patients were on regular prednisolone
(range, 2 to 10 mg/d) and 11 on daily theophylline, 400 mg. The
14 patients who did not complete the study were not significantly different from the 70 who did, in any baseline parameters shown in Table 1. Diary card PEFR data were recorded for
a mean of 307 6 49 or for 84 6 13% of the year study period.
Exacerbations

There were 190 exacerbations (mean 2.7; median 3; range, 1 to

8) in the 70 patients over the year of follow-up. Six unreported
exacerbations were treated at other centers with no recording
on their diary cards; these were therefore excluded from further analyses. Of the 184 exacerbations, 93 were reported,
providing a reporting rate of 1.5 per patient per year. There
were no differences between reported and unreported exacerTABLE 1
CLINICAL AND PHYSIOLOGICAL DATA AT
START OF STUDY (n 5 73)
Mean

SD

67.8
1.05
40
6.7
2.48
44
235
66
45.6
1.11
3.0

8.3
0.45
19
9.1
0.82
15
89
8.3
7.2
0.66
2.6

Daily symptoms

Cough
Sputum
Cough and sputum
Wheeze
Dyspnea

58
62
45
34
49

42
45
33
25
36

Age, yr
FEV1, L
FEV1, %
FEV1 reversibility, %
FVC, L
FEV1/FVC, %
PEFR, L/min
PaO2, mm Hg
PaCO2, mm Hg
Daily inhaled steroids, mg
Past exacerbations*

* Exacerbations in year prior to recruitment.

1420

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

VOL 157

1998

TABLE 2
RELATIONSHIP BETWEEN SGRQ SCORES AND EXACERBATION FREQUENCY
Exacerbation
Frequency
02
38
Mean difference
CI
p Value

Total

Symptoms

Activities

Impacts

32
38

48.9 6 15.6
64.1 6 14.6
215.1
222.3 to 27.8
, 0.0005

53.2 6 17.2
77.0 6 15.8
221.9
229.7 to 214.0
, 0.0005

67.7 6 17.2
80.9 6 16.0
212.2
221.2 to 25.3
0.001

36.3 6 18.2
50.4 6 17.6
214.1
222.9 to 25.6
0.002

Definition of abbreviation: CI 5 95% confidence interval.

* Mean 6 SD.

bations for the major symptoms (p . 0.15). For the minor

symptoms, reported exacerbations were associated with a
higher incidence of increased cough (p 5 0.02), but a lower incidence of increased wheeze (p 5 0.03). There were no differences in PEFR fall over the 2 d prior to exacerbation (p 5
0.77) nor duration of PEFR change at exacerbation (p 5 0.41).
There was no difference in reporting rate between the first
and second 6 mo of the study (p 5 0.85).
At exacerbation the PEFR fell by a median [interquartile
range (IQR)] of 6.6 (216.6, 0) L/min (p 5 0.0003). Recovery
of PEFR to baseline occurred after 11.1 6 6.1 d. Seventeen
patients were admitted to the hospital for a total of 23 exacerbations. There was no difference in PEFR change at exacerbation between those who were admitted for exacerbation and
those who were not (p 5 0.95).
Quality-of-life Scores

The mean (6 SD) SGRQ Total score for the cohort was
56.7 6 16.7 (component scores: Impacts, 43.5 6 19.1, Symptoms 66.4 6 19.8, and Activities 74.5 6 17.8). The mean time
between completion of the SGRQ and the preceding exacerbation was 101 6 74 d. The Total quality-of-life score was
worse in MRC grades 4 and 5 patients (p 5 0.002), among
younger patients (p 5 0.0029), and those with frequent past
exacerbations (p 5 0.0014). Wheeze was the only daily symptom associated with a reduced quality of life. Blood gases and
lung function showed no association with the SGRQ Total
score. The Symptom score was worse for patients with frequent past exacerbations (r 5 0.45, p 5 0.0005), daily wheeze
(r 5 0.39, p 5 0.001), daily sputum (r 5 0.30, p 5 0.011), bronchitic symptoms (r 5 0.26, p 5 0.03), and daily dyspnea (r 5
0.27, p 5 0.023). The Activities score was higher with frequent
past exacerbations (r 5 0.24, p 5 0.047) and with MRC Groups
4 and 5 (r 5 0.37, p 5 0.002) and was related to FEV1 (r 5
20.26, p 5 0.03). The Impact score was worse in younger patients (r 5 20.39, p 5 0.001) frequent past exacerbations (r 5
0.26, p 5 0.033), MRC Groups 4 and 5 (r 5 0.35, p 5 0.003),
and in patients with wheeze (r 5 0.39, p 5 0.001). Table 2
shows that SGRQ Total and component scores were all significantly higher in patients who had frequent exacerbations (p ,
0.005). There was a 15-point mean difference in SGRQ Total
score between the frequent and infrequent exacerbators.
Factors Predisposing to Frequent Exacerbations

Exacerbations were more frequent in patients with frequent

past exacerbations (odds ratio [OR] 5 5.5, p 5 0.001), those
with daily cough (OR 5 3.3, p 5 0.019), or daily wheeze
(OR 5 4.2, p 5 0.011). Exacerbation frequency was also related to bronchitic symptoms (OR 5 3.8, p 5 0.009), but not
to daily sputum production alone nor dyspnea. No other baseline factors or PEFR change at exacerbation were related to

exacerbation frequency. When all factors were taken together,

three factors that showed a univariate association with exacerbation frequency contributed independently to exacerbation
frequency: frequent past exacerbations (OR 5 1.43, p 5
0.013), daily wheeze (OR 5 1.34, p 5 0.042), and bronchitic
symptoms (OR 5 1.56, p 5 0.009).
SGRQ Scores and Predisposing Factors

Table 3 shows the multiple regression analyses between the

SGRQ scores and the factors predictive of either a high exacerbation frequency or showing a univariate association with
SGRQ. The exacerbation frequency was strongly correlated
to the SGRQ Total and each of the component scores. Inclusion of time to preceding exacerbation did not affect the regression. Past exacerbations were only related to the SGRQ
Symptoms score (p 5 0.0428). MRC grade was significantly related to the SGRQ Total, Impacts, and Activities scores. SGRQ
score was not related to PEFR changes at exacerbation nor to
frequency of hospital admissions (p . 0.59 in all cases). This
model accounted for 46% of the variance in SGRQ Total score
and 40% of that in the Symptoms component.

DISCUSSION
This study was designed to evaluate the effect of exacerbations on health status in COPD patients, and to determine the
predisposing factors to exacerbations. Patients were monitored daily at home and asked to report exacerbations as soon
as possible after onset. Health status, measured with the SGRQ,

TABLE 3
MULTIPLE REGRESSION ANALYSIS WITH THE SGRQ SCORES
AS OUTCOME VARIABLES (n 5 70)
R2
SGRQ Total score
Exacerbation frequency
MRC grades 4 and 5
Daily wheeze
Age
SGRQ Symptoms
Exacerbation frequency
Past exacerbations
SGRQ Activities
Exacerbation frequency
MRC grades 4 and 5
SGRQ Impacts
Exacerbation frequency
Daily wheeze
MRC grades 4 and 5
Age
* b 5 regression coefficient.

b*

SE b*

p Value

11.54
12.68
7.83
20.46

3.26
3.04
3.48
0.19

0.0008
0.0001
0.0280
0.0207

16.1
8.69

4.18
4.21

0.0003
0.0428

13.44
13.28

3.71
3.72

0.0006
0.0007

9.18
10.23
13.84
20.66

3.84
4.10
3.63
0.23

0.0200
0.0152
0.0003
0.0056

0.46

0.40

0.29

0.41

Seemungal, Donaldson, Paul, et al.: Effect of Exacerbation on QOL in COPD

was strongly related to the number of exacerbations over the

year study period and to the number of past exacerbations.
Patients with COPD develop significant disability with progressive disease, and measures of lung function such as FEV1
may not accurately predict disability (18, 19). Respiratory diseasespecific questionnaires, such as the SGRQ, provide sensitive measurements of disturbance to daily life and well-being.
The SGRQ has been evaluated in patients with all grades of
severity of COPD, including chronic respiratory failure (2, 7,
20) and correlates quite well with exercise capacity (3, 6, 21).
Although the level of the FEV1 was not predictive of exacerbation in this study, the SGRQ Total and three component
scores all related strongly to exacerbation frequency. Thus a
high SGRQ score may be used to predict patients at risk from
frequent exacerbations. As the SGRQ was administered at the
last clinic visit we cannot be certain that reduced health status
is a consequence of high exacerbation frequency. Because the
mean time between administering the SGRQ and the preceding exacerbation was 101 d, it is unlikely that a current exacerbation affected the response. In bronchiectatic patients, SGRQ
scores were also found to be related to the exacerbation frequency (22). In our study the MRC dyspnea score was strongly
related to SGRQ scores, but not to exacerbation frequency;
thus indicating that while dyspnea is a weak discriminating factor for frequent exacerbations, it is associated with reduced
quality of life. PEFR changes at exacerbation, though significant, were not related to SGRQ scores.
Patients were asked to report exacerbations according to
worsening of symptoms. However, despite considerable instruction and clinic visits, only 50% of the exacerbations were
reported. The reporting rate in this study is comparable to a
study in children with asthma, where 33% of exacerbations
were reported (23). Patients with COPD are accustomed to
frequent symptom changes and thus may tend to underreport
exacerbations to physicians. These patients have high levels of
anxiety and depression and may accept their situation (7),
though there is no evidence that unreported exacerbations led
to increased morbidity. There were no differences in any of
the major symptoms, exacerbation frequency, duration, or peak
flow changes between reported or unreported exacerbations,
though reported exacerbations were associated with changes
in the minor symptoms; a greater incidence of cough and less
wheeze. We found no differences in PEFR changes in those
presenting with cough and/or wheeze, and thus for analysis,
combined reported and unreported exacerbations. The tendency
of patients to underreport exacerbations may explain the higher
total rate of exacerbation of 2.7 per patient per year detected
in this study as compared with that reported by Anthonisen
and coworkers (15) where the exacerbation rate was 1.1 per
patient per year and unreported exacerbations were diagnosed
from patients recall of symptoms.
A previous study of acute infective exacerbations of
chronic bronchitis found that one of the factors predicting exacerbation was the number in the previous year (24). However, this study was limited to exacerbations presenting with
purulent sputum only, without bacteriological evidence of infection and no baseline or exacerbation-related physiological
data was available. We also found that patients with frequent
past exacerbations were more likely to have an exacerbation
during the study year. Patients who had chronic cough or
wheeze also tended to have a higher exacerbation frequency,
though frequency was not related to chronic sputum production. Patients with chronic productive cough may be more susceptible to infection, or to environmental factors such as air
pollution, temperature changes, or humidity.
Coexisting cardiac and pulmonary disease has been previ-

1421

ously identified as the only other risk factor for exacerbations

(24). We found no relationship between congestive cardiac
failure, ischemic heart disease, and exacerbation frequency,
but this may be due to the relatively small number of patients
with cardiac disease in this study. However our study revealed
a strong relationship between bronchitic symptoms and exacerbation frequency. Jousilahti and colleagues (25) found that
the presence of bronchitic symptoms predicted the risk of coronary artery disease independently of other known risk factors. Thus there may be an association between exacerbation
frequency and coronary artery events in COPD patients.
In our study, only 16% of the exacerbations required hospital admission; this is representative of community-acquired
COPD exacerbations. There was no relation between hospital
admission and exacerbation frequency. One recent retrospective study found a relationship between poor quality-of-life
measures and hospital readmission (8). However, reasons for
hospital admission are complex, with patients with COPD exacerbations often admitted to the hospital late in the evolution
of the disease, when usual therapy has failed. The purpose of
this study was to consider COPD exacerbations at onset in the
community as commonly found in clinical practice before secondary complications have occurred.
This study shows that COPD exacerbation may have important effects on health status and is a useful outcome measure in clinical studies of the disease. Reduction of exacerbation frequency would be expected to improve well-being, though
this has not been formally tested in an interventional study.
Health status measures show a strong relationship with exacerbation frequency and thus may be useful in determining which
patients are at risk of exacerbation and associated disability.
Earlier identification of patients at particular risk may considerably reduce the morbidity and mortality from complications
associated with COPD exacerbations.
Acknowledgment : The writers thank Claire Evans for help in data collection, and the staff of the Respiratory Function unit of the London Chest
Hospital for assistance with physiological measurements.

References
1. Fletcher, C., and R. Peto. 1977. The natural history of chronic airflow
obstruction. B.M.J. 1:16451648.
2. Jones, P. W., F. H. Quirk, C. M. Baveystock, and P. Littlejohns. 1992. A
self-complete measure for chronic airflow limitation: The St. Georges
Respiratory Questionnaire. Am. Rev. Respir. Dis. 145:13211327.
3. Guyatt, G. H., L. B. Berman, M. Towensend, S. O. Pugsley, and L. W.
Chambers. 1987. A measure of quality of life for clinical trials in
chronic lung disease. Thorax 42:773778.
4. Ketelaars, C. A. J., M. A. G. Schlosser, R. T. Mostert, H. H. Abu-Saad,
R. J. G. Halfens, and E. F. M. Wouters. 1996. Determinants of healthrelated quality of life in patients with chronic obstructive pulmonary
disease. Thorax 51:3943.
5. Jones, P. W., and T. K. Bosh. 1997. Quality of life changes in COPD patients treated with salmeterol. Am. J. Respir. Crit. Care Med. 155:1283
1289.
6. McSweeney, A. J., R. K. Heaton, I. Grant, D. Cugell, N. N. Solliday, and
R. Timms. 1982. Chronic obstructive pulmonary disease: socioemotional adjustment and quality of life. Chest 77:309311.
7. Okubadejo, A. A., P. W. Jones, and J. A. Wedzicha. 1996. Quality of life
in patients with chronic obstructive pulmonary disease and severe hypoxaemia. Thorax 51:4447.
8. Osman, L. M., D. J. Godden, J. A. R. Friend, J. S. Legge, and J. G. Douglas. 1997. Quality of life and hospital re-admission in patients with
chronic obstructive pulmonary disease. Thorax 52:6771.
9. Traver, G. A. 1988. Measures of symptoms and life quality to predict
emergent use of institutional health care resources in chronic obstructive airways disease. Heart Lung 17:689697.
10. Siu, A. L., D. B. Reuben, J. G. Ouslander, and D. Osterweil. 1993. Using
multidimensional health measures in older persons to identify risk of
hospitalisation and skilled nursing placement. Quality of Life Res. 2:

1422

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

253261.
11. Cox, N. J., L. C. Hendricks, R. A. Binkhorest, and C. L. van Heywaarden. 1993. A pulmonary rehabilitation program for patients with
asthma and mild chronic obstructive pulmonary diseases (COPD).
Lung 171:235244.
12. American Thoracic Society. 1995. Standards for the diagnosis and care
of patients with chronic obstructive pulmonary disease. Am. J. Respir.
Crit. Care Med. 152:S78S83.
13. Nagai, A., W. M. Thurlbeck, and K. Konno. 1995. Responsiveness and
variability of airflow obstruction in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 151:635639.
14. Pitkin, A. D., C. M. Roberts, and J. A. Wedzicha. 1994. Arterialised ear
lobe blood gas analysis: an underused technique. Thorax 49:364366.
15. Anthonisen, N. R., J. Manfreda, C. P. W. Warren, E. S. Hershfield,
G. K. M. Harding, and N. A. Nelson. 1994. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann. Intern. Med.
106:196204.
16. Quirk, F. H., and P. W. Jones. 1990. Patients perceptions of distress due
to symptoms and effect of asthma on daily living and investigation of
possible influential factors. Clin. Sci. 79:1721.
17. Medical Research Council Committee on Aetiology of Chronic Bronchitis. 1960. Standardised questionnaires on respiratory symptoms. B.M.J.
2:1665.
18. McGavin, C. R., S. P. Gupta, and G. J. McHardy. 1976. Twelve minute
walking test for assessing disability in chronic bronchitis. B.M.J. 1:
6073;822823.

VOL 157

1998

19. Killian, K. J., E. Summer, N. L. Jones, and E. J. Campbell. 1992. Dyspnea and leg effort during incremental cycle ergometry. Am. Rev. Respir. Dis. 145:13391345.
20. Meecham Jones, D. J., E. A. Paul, P. W. Jones, and J. A. Wedzicha.
1995. Nasal pressure support ventilation plus oxygen compared with
oxygen therapy alone in hypercapneic COPD. Am. J. Respir. Crit.
Care Med. 152:538544.
21. Jones, P. W., C. M. Baveystock, and P. Littlejohns. 1989. Relationship
between general health measured with sickness impact profile and
respiratory symptoms physiologic measures and mood in patients with
chronic airflow limitation. Am. Rev. Respir. Dis. 140:15381543.
22. Wilson, C. B., P. W. Jones, C. J. OLeary, P. J. Cole, and R. Wilson. 1997.
Validation of the St. Georges Respiratory Questionnaire in bronchiectasis. Am. J. Respir. Crit. Care Med. 156:536541.
23. Johnston, S. L., P. K. Pattemore, G. Sanderson, S. Smith, F. Lampe, L.
Josephs, P. Symington, S. OToole, S. H. Myint, D. A. Tyrrell, and
S. T. Holgate. 1995. Community study of role of viral infections in exacerbations of asthma in 911 year old children. B.M.J. 310:1225
1229.
24. Ball, P., J. M. Harris, D. Lowson, G. Tillotson, and R. Wilson. 1995.
Acute infective exacerbations of chronic bronchitis. Q. J. Med. 88:61
68.
25. Jousilahti, P., E. Variainen, J. Tuomilehto, and P. Puska. 1996. Symptoms of chronic bronchitis and the risk of coronary disease. Lancet
348:567572.