Daily activity during stability and exacerbation of chronic obstructive pulmonary disease
© Alahmari et al.; licensee BioMed Central Ltd. 2014
Received: 4 February 2014
Accepted: 21 May 2014
Published: 2 June 2014
During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data.
Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators.
The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted. They recorded pedometer data on a median 198 days (IQR 134–353). At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min. Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).
Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002).
COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time.
KeywordsCOPD Exacerbation Daily step-count Physical activity Daily monitoring
Chronic obstructive pulmonary disease (COPD) is a global cause of morbidity and mortality and an impairment of health status . Patients with COPD experience episodes of acute worsening of respiratory symptoms termed exacerbations, often triggered by infections . Frequent exacerbations are a stable feature of the disease  and have important impacts, such as, accelerating decline in lung function, reducing quality of life and impose higher health care utilization and costs [3–5]. Respiratory symptoms following an exacerbation can take a number of weeks to return to baseline . COPD patients are less likely to go outside during an exacerbation . Also, patients with frequent exacerbations experience a significant faster decline in the amount of time spent outdoors . Depression is a significant comorbid condition in COPD patients  and associated with increased risk of exacerbation and hospitalisation .
COPD although primarily affecting the respiratory system is known to have extra pulmonary effects such reduced patient activity and skeletal muscle dysfunction. Studies using accelerometers have shown that activity declines at exacerbation especially in hospitalized patients in comparison to a month later [10, 11] and over time . Low levels of physical activity assessed with a multisensory arm-band (SenseWear) is strongly associated with all-cause mortality in patients with COPD  and data from an ankle-worn accelerator independently predicts exacerbation frequency .
Most clinical trials of early post-exacerbation pulmonary rehabilitation (PR) trials have shown significant improvement in exercise capacity, skeletal muscle strength, dyspnoea, quality of life and prevent de-conditioning [15–17]. Despite this evidence, patients treated in the community for an exacerbation are not actively encouraged to maintain their physical activity during exacerbation recovery. Possibly, information is lacking concerning the extent that physical activity decreases during these non-hospitalized events. These data would be needed for determining the sample size required for a clinical trial of early PR in community treated exacerbations.
Prospective monitoring of physical activity is necessary for quantifying the effects of exacerbation on activity as baseline measurements falls over time and may vary with season. Accelerometer-based monitoring devices are expensive and require regular clinic visits to download the data and are therefore not ideal for the long-term use required to prospectively capture relatively rare events such as exacerbations. Accelerometers may slightly under-estimate step count at the slow walking speeds expected in COPD patients . Pedometers are cheap and simple to use, but there is little published data to support their use in COPD patients. The aims of this study were to prospectively evaluate daily step-count determined with a simple pedometer, before and during the onset and recovery of an exacerbation. We have also evaluated the longitudinal trend of daily activity in patients with a history of frequent and infrequent exacerbations.
Patient recruitment and characteristics
Seventy three patients were recruited from the London COPD cohort. These patients recorded daily pedometry data for a minimum of 35 days with the initial 7 days considered as training and discarded for the purposes of analysis. The study took place over 19 months between April 2011 and November 2012.
All 199 patients in our rolling cohort were considered for participation in this study. 24 patients were not eligible as they used a walking support (cane or frame), were confined to a wheel chair or used ambulatory oxygen cylinders; 30 refused. We eventually provided pedometers to 145 patients. Data was successfully acquired from only 73 patients due to the following reasons a) 21 patients once issued refused to use the pedometer b) 19 patients lost their pedometers c) 23 patients recorded less than 35 days of data whilst stable d) 9 pedometers malfunctioned.
COPD was defined as a post-bronchodilator forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio below 0.70 and FEV1 expressed as a percentage of predicted FEV1 of less than 80%. Patients were categorised as moderate, severe or very severe according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification . Patients with a history of another significant respiratory disease or considered unable to complete daily diary cards excluded . Patients were recruited when clinically stable, at least six weeks after their last exacerbation.
At recruitment, age, gender, chronic respiratory symptoms and smoking history were noted, and height and weight measured. FEV1 and FVC were measured with a Vitalograph Gold Standard spirometer (Vitalograph Ltd, Maids Moreton, UK).
All patients were asked to complete a daily diary card on which they recorded their morning post-medication peak expiratory flow (PEF) measured with a mini-Wright peak-flow meter (Clement-Clarke International Ltd, Harlow, UK). They also recorded any worsening in their respiratory symptoms above normal and the number of hours spent outside their home.
Patients were also instructed to wear a Yamax Digi-walker SW-200 pedometer on the left side of their body [20, 21] all the time, except when sleeping or showering. Pedometer placement was standardized by placing it on the belt or waistband, in the midline of the thigh, consistent with the manufacturer’s recommendation . This pedometer has been shown to accurately measure steps in free-living individuals  and in normal and moderately obese patients and  detected differences in physical activity of COPD patients recorded their daily step count on the diary cards.
An exacerbation was defined as an increase for two consecutive days in respiratory symptoms, with at least one major symptom (dyspnoea, sputum purulence or sputum volume) plus either another major or a minor symptom (wheeze, cold, sore throat, and cough)  .Five consecutive symptom free days were required before identification of the next exacerbation. Symptoms were disregarded in identifying exacerbation onset if recorded continuously in the preceding 5 days .A small proportion of exacerbations for which no diary-card symptoms had been recorded by questioning the patient at clinic visits about any recent prescriptions  Symptom counts were obtained by summating each increased respiratory symptom recorded on diary cards per day.
Patients were then divided into two groups, based on the number of exacerbations in the 12 months preceding the start of the study, those with 2 or more exacerbations per year were called frequent exacerbators and those with 0 or 1 exacerbation per year called infrequent exacerbators .
Changes at exacerbations in daily step-count, symptoms count, PEF and hours spent outdoors were assessed by comparison of the average value over a 7 day baseline period which started 2 weeks before onset with the average value over a 7 days exacerbation period starting on the day of exacerbation onset. Recovery was determined as the day after exacerbation onset when a 3 day moving average of a parameter matched or exceeded its baseline value. A moving average was used to avoid false early recoveries when step count or lung function improved for just a single day, but then remained below baseline for a few more days .
The study was approved by the London-Hampstead research ethics committee and all patients gave written informed consent (REC 09/H0720/8). The current study is entirely novel and has not been reported before except in abstract form (European Respiratory Society Annual Congress 2013, Barcelona, Spain 7–11 September).
Data were analyzed with STATA 8.2 (Stata Corporation, College Station, TX) and PASW statistics V.21 (SPSS Inc.). Normally distributed data are reported as a mean and standard deviation (SD) or standard error of the mean (SEM) and skewed data reported with a median and inter quartile range (IQR). Comparisons were made by paired Student t test or Wilcoxon signed-rank test as appropriate. Stable mean daily step count and other patient characteristics were related with a Pearson correlation or Spearman rank correlation. Random effect linear regression models were used to assess annual decline in daily stable step count and whether the decline was faster in frequent than infrequent exacerbators. A stable step count was defined as outside a period starting 2 weeks before and ending 2 weeks after an exacerbation. Data from patients who experienced multiple exacerbations were averaged to avoid bias through repeated measures. However, we analyzed exacerbations as individual events when investigating whether the characteristics of exacerbations (respiratory symptoms, treatment, change in step count) was associated with a fall in activity or recovery. Significant was taken as p < 0.05.
Characteristics of the 73 COPD patients in the study and 126 COPD patients in the Cohort not recruited to the study
73 COPD patients
Remaining 126 COPD patients in the Cohort
FEV 1 (l)
FEV 1 (% predicted)
FEV 1 /FVC (%)
BMI (kg/m 2 )
( IQR )
( IQR )
Smoking at recruitment
Decline of daily step-count between patients with frequent and infrequent exacerbations
Time course of daily step-count at COPD exacerbation
Thirty seven patients experienced 79 exacerbations and the characteristics of these patients are reported as additional file table (see Additional file 1: Table S1). The median time since the last exacerbation was 85.5 days (IQR 42–193). The shortest interval was 15 days. There was no record of a preceding exacerbation for 7 exacerbations as these patients had been recently recruited. There were no significant differences in patient characteristics between these 37 patients and the 36 who did not experience an exacerbation except a higher FVC (L).
Comparison between baseline and first 7 days of exacerbation (mean ± SD)
Daily step-counts (step/day)
Peak Expiratory Flow (L/Min)
Time outdoors (hours/day)
Percentage of days on which patient went outdoors (%)
The relationship between fall in daily steps–count and respiratory symptoms and activity recovery
Activity and treatment
This is the first and largest study to report fall and recovery in daily walking activity using pedometry in ambulatory COPD patients during non-hospitalized exacerbations. We found that daily step count fell by 480 steps per day during exacerbation and recovery took a median 3.5 days. Over time, daily step count fell faster in patients with frequent exacerbations. We also observed that exacerbations associated with a fall in daily step count were more likely to be reported and received treatment.
Previous work on activity during exacerbation recovery has been mainly based on the study of hospitalised COPD patients. Pitta and colleagues saw improvements in time spent walking in hospital compared to one month after discharge, but they observed no difference between day 2 and day 7 . Borges and colleagues have shown that daily step count assessed with a tri-axial accelerometer increased from 602 steps/day on the 2nd day of hospitalisation to 3,575 steps/day at one month post discharge (p < 0.001) in 32 patients . However, activity monitoring during exacerbations that required hospitalisations may not reflect patient behaviour during exacerbations taking place in the community as hospitalised patients are likely to stay in bed for prolonged periods and not undertake their usual activities. Furthermore, these hospital based studies did not collect data prior to the onset of the exacerbation. In a recently published small study, Ehsan reported on activity levels in 17 patients who had just 27 symptom-define (EXACT) exacerbation in the community  but daily data was lacking.
In this study we found that respiratory symptoms took longer than daily step-count or time outdoors to return to baseline values. The reasons for an earlier recovery in activity are unclear, but may be due to the need to go out of the home for social reasons or shopping, perhaps to return to work or a desire to exercise after a period of being housebound. It is also possible that the severity of the respiratory symptoms during the later stages of recovery is not sufficient to inhibit activity. In a previous study, on 1465 exacerbations, we reported that patients are significantly less likely to leave their home during an exacerbation . In this study, we observed a similar trend, but it did not reach statistical significance due to the smaller patient numbers studied. As daily step count fell but hour’s outdoors was unchanged relative to the baseline, it might be that patients with an exacerbation used transport or walked more slowly when outside the home. The actual intensity and nature of exercise undertaken is a question that can only be addressed by more sophisticated accelerometer devices.
The present study shows that the larger the fall in the daily step count at exacerbation the longer it takes activity to return to normal. This suggests that COPD patients should be encouraged to keep active during the early stages of exacerbation since activity will return to normal faster. Pulmonary rehabilitation programmes initiated early post-exacerbation show a benefit compared to usual care [15–17, 26–28] possibly by avoiding muscle deconditioning through inactivity during bed-rest . However, in the largest study to date, Eaton and colleagues found no significant effect on acute health-care utilization, although it was found to be safe and feasible .
Treated exacerbations were slower to recovery compared to untreated exacerbations though our previous work has suggested there is little difference in respiratory symptoms between treated and untreated events . The reasons why patients report some exacerbations to a health care professional and not others have been unclear and approximately 50% of exacerbations are unreported [4, 31]. Our findings suggest that impairment of daily activity may be a key factor in patients seeking additional therapy for their exacerbation.
This study has shown for the first time that patients who experienced frequent exacerbations have twice as fast an annual decline in daily step-count than patients with infrequent exacerbations. Frequent exacerbations are known to accelerate both decline in FEV1 and rise in airway and systemic inflammation [3, 32] with patients becoming housebound faster , and more likely to suffer from depression  and fatigue . The precise mechanism of activity decline is unclear but it is possible that prolonged recovery or non-recovery after an exacerbation may contribute to this decline. In addition, anxiety, depression and fatigue are associated with exacerbations and any discourage patients from maintaining activity. This may be particularly marked in more severe patients with frequent exacerbations as they have significantly more and longer hospital admissions, though hospital admissions were not a subject for this study. Cote and colleagues found a reduction in exercise capacity after an exacerbation, with a 72 m decline (20%) in 6MWD .
An important strength of the study was the prospective daily monitoring of COPD patients to capture a baseline activity level just before the exacerbation event started. Baseline data collected away from the exacerbation may not be valid as daily step count declines over time and varies with seasonal changes . Daily monitoring is also essential when investigating exacerbation where symptoms recovery to normal in a few days. One limitation of the study is that we did not include patients using ambulatory oxygen or walking supports or mild patients with GOLD stage 1 COPD and our results should not be extrapolated to these patient groups. However an important feature of this study is that exacerbations treated in the community were included and this makes the data applicable to the majority of exacerbations experienced by COPD patients.
Pedometer measurements can be used to track daily activity easily during COPD exacerbations that do not require hospital admission. We have shown that exacerbations reduce physical activity with patients recovering within a 3 to 4 day period. Frequent exacerbations also hasten a decline in activity over time and potentially this patient group would benefit from greater encouragement to continue exercising. Our results also show that daily activity is a major drive for patients reporting exacerbation events and seeking additional therapy. Thus, non-hospitalized COPD exacerbations are key events that not only cause symptomatic deterioration but also impair the patients’ activity.
Chronic Obstructive Pulmonary Disease
Peak expiratory flow
Forced expiratory volume in one second
Forced vital capacity
Global initiative for chronic obstructive lung disease
Standard error of the mean
Inter quartile range
The authors are grateful to all the patients in the London COPD cohort who have contributed to the study, and willing give up their time to perform assessment for this work.
The London COPD Cohort was funded by the Medical Research Council (MRC), UK. Patient Cohort Grant G0800570/1. AA is funded by the Saudi Ministry of Higher Education, the Kingdom of Saudi Arabia. The funding body had no input into any aspect of this study.
- Wedzicha JA, Seemungal TA: COPD exacerbations: defining their cause and prevention. Lancet. 2007, 370: 786-796. 10.1016/S0140-6736(07)61382-8.View ArticlePubMedGoogle Scholar
- Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, Calverley P, Rennard S, Wouters EF, Wedzicha JA: Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010, 363: 1128-1138. 10.1056/NEJMoa0909883.View ArticlePubMedGoogle Scholar
- Donaldson GC, Seemungal TA, Patel IS, Bhowmik A, Wilkinson TM, Hurst JR, Maccallum PK, Wedzicha JA: Airway and systemic inflammation and decline in lung function in patients with COPD. Chest. 2005, 128: 1995-2004. 10.1378/chest.128.4.1995.View ArticlePubMedGoogle Scholar
- Seemungal TA, 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: 1418-1422. 10.1164/ajrccm.157.5.9709032.View ArticlePubMedGoogle Scholar
- Simon-Tuval T, Scharf SM, Maimon N, Bernhard-Scharf BJ, Reuveni H, Tarasiuk A: Determinants of elevated healthcare utilization in patients with COPD. Respir Res. 2011, 12: 7-10.1186/1465-9921-12-7.View ArticlePubMedPubMed CentralGoogle Scholar
- Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA: Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000, 161: 1608-1613. 10.1164/ajrccm.161.5.9908022.View ArticlePubMedGoogle Scholar
- Donaldson GC, Wilkinson TM, Hurst JR, Perera WR, Wedzicha JA: Exacerbations and time spent outdoors in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005, 171: 446-452. 10.1164/rccm.200408-1054OC.View ArticlePubMedGoogle Scholar
- Norwood R: Prevalence and impact of depression in chronic obstructive pulmonary disease patients. Curr Opin Pulm Med. 2006, 12: 113-117. 10.1097/01.mcp.0000208450.50231.c6.View ArticlePubMedGoogle Scholar
- Xu W, Collet JP, Shapiro S, Lin Y, Yang T, Platt RW, Wang C, Bourbeau J: Independent effect of depression and anxiety on chronic obstructive pulmonary disease exacerbations and hospitalizations. Am J Respir Crit Care Med. 2008, 178: 913-920. 10.1164/rccm.200804-619OC.View ArticlePubMedGoogle Scholar
- Borges RC, Carvalho CR: Physical activity in daily life in Brazilian COPD patients during and after exacerbation. COPD. 2012, 9: 596-602. 10.3109/15412555.2012.705364.View ArticlePubMedGoogle Scholar
- Pitta F, Troosters T, Probst VS, Spruit MA, Decramer M, Gosselink R: Physical activity and hospitalization for exacerbation of COPD. Chest. 2006, 129: 536-544. 10.1378/chest.129.3.536.View ArticlePubMedGoogle Scholar
- Ehsan M, Khan R, Wakefield D, Qureshi A, Murray L, Zuwallack R, Leidy NK: A Longitudinal Study Evaluating the Effect of Exacerbations on Physical Activity in Patients with Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc. 2013, 10: 559-564. 10.1513/AnnalsATS.201304-100OC.View ArticlePubMedGoogle Scholar
- Waschki B, Kirsten A, Holz O, MÃžller K-C, Meyer T, Watz H, Magnussen H: Physical activity is the strongest predictor of all-cause mortality in patients with COPDPhysical activity and all-cause mortality in COPDA prospective Cohort Study. CHEST J. 2011, 140: 331-342. 10.1378/chest.10-2521.View ArticleGoogle Scholar
- Moy ML, Danilack VA, Weston NA, Garshick E: Daily step counts in a US cohort with COPD. Respir Med. 2012, 106: 962-969. 10.1016/j.rmed.2012.03.016.View ArticlePubMedPubMed CentralGoogle Scholar
- Man WD, Polkey MI, Donaldson N, Gray BJ, Moxham J: Community pulmonary rehabilitation after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease: randomised controlled study. BMJ. 2004, 329: 1209-10.1136/bmj.38258.662720.3A.View ArticlePubMedPubMed CentralGoogle Scholar
- Murphy N, Bell C, Costello RW: Extending a home from hospital care programme for COPD exacerbations to include pulmonary rehabilitation. Respir Med. 2005, 99: 1297-1302. 10.1016/j.rmed.2005.02.033.View ArticlePubMedGoogle Scholar
- Kirsten DK, Taube C, Lehnigk B, Jorres RA, Magnussen H: Exercise training improves recovery in patients with COPD after an acute exacerbation. Respir Med. 1998, 92: 1191-1198. 10.1016/S0954-6111(98)90420-6.View ArticlePubMedGoogle Scholar
- Furlanetto KC, Bisca GW, Oldemberg N, Sant’anna TJ, Morakami FK, Camillo CA, Cavalheri V, Hernandes NA, Probst VS, Ramos EM, Brunetto AF, Pitta F: Step counting and energy expenditure estimation in patients with chronic obstructive pulmonary disease and healthy elderly: accuracy of 2 motion sensors. Arch Phys Med Rehabil. 2010, 91: 261-267. 10.1016/j.apmr.2009.10.024.View ArticlePubMedGoogle Scholar
- Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013, 187: 347-365. 10.1164/rccm.201204-0596PP.View ArticlePubMedGoogle Scholar
- Schneider PL, Crouter SE, Lukajic O, Bassett DR: Accuracy and reliability of 10 pedometers for measuring steps over a 400-m walk. Med Sci Sports Exerc. 2003, 35: 1779-1784. 10.1249/01.MSS.0000089342.96098.C4.View ArticlePubMedGoogle Scholar
- Crouter SE, Schneider PL, Karabulut M, Bassett DR: Validity of 10 electronic pedometers for measuring steps, distance, and energy cost. Med Sci Sports Exerc. 2003, 35: 1455-1460. 10.1249/01.MSS.0000078932.61440.A2.View ArticlePubMedGoogle Scholar
- Schneider PL, Crouter S, Bassett DR: Pedometer measures of free-living physical activity: comparison of 13 models. Med Sci Sports Exerc. 2004, 36: 331-335. 10.1249/01.MSS.0000113486.60548.E9.View ArticlePubMedGoogle Scholar
- Swartz AM, Bassett DR, Moore JB, Thompson DL, Strath SJ: Effects of body mass index on the accuracy of an electronic pedometer. Int J Sports Med. 2003, 24: 588-592.View ArticlePubMedGoogle Scholar
- Hurst JR, Donaldson GC, Quint JK, Goldring JJ, Baghai-Ravary R, Wedzicha JA: Temporal clustering of exacerbations in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009, 179: 369-374. 10.1164/rccm.200807-1067OC.View ArticlePubMedGoogle Scholar
- Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA: Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002, 57: 847-852. 10.1136/thorax.57.10.847.View ArticlePubMedPubMed CentralGoogle Scholar
- Troosters T, Gosselink R, Decramer M: Short- and long-term effects of outpatient rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial. Am J Med. 2000, 109: 207-212. 10.1016/S0002-9343(00)00472-1.View ArticlePubMedGoogle Scholar
- Nava S: Rehabilitation of patients admitted to a respiratory intensive care unit. Arch Phys Med Rehabil. 1998, 79: 849-854. 10.1016/S0003-9993(98)90369-0.View ArticlePubMedGoogle Scholar
- Behnke M, Jorres RA, Kirsten D, Magnussen H: Clinical benefits of a combined hospital and home-based exercise programme over 18 months in patients with severe COPD. Monaldi Arch Chest Dis. 2003, 59: 44-51.PubMedGoogle Scholar
- Troosters T, Probst VS, Crul T, Pitta F, Gayan-Ramirez G, Decramer M, Gosselink R: Resistance training prevents deterioration in quadriceps muscle function during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010, 181: 1072-1077. 10.1164/rccm.200908-1203OC.View ArticlePubMedGoogle Scholar
- Eaton T, Young P, Fergusson W, Moodie L, Zeng I, O’Kane F, Good N, Rhodes L, Poole P, Kolbe J: Does early pulmonary rehabilitation reduce acute health-care utilization in COPD patients admitted with an exacerbation? A randomized controlled study. Respirology. 2009, 14: 230-238. 10.1111/j.1440-1843.2008.01418.x.View ArticlePubMedGoogle Scholar
- Langsetmo L, Platt RW, Ernst P, Bourbeau J: Underreporting exacerbation of chronic obstructive pulmonary disease in a longitudinal cohort. Am J Respir Crit Care Med. 2008, 177: 396-401. 10.1164/rccm.200708-1290OC.View ArticlePubMedGoogle Scholar
- Patel IS, Seemungal TA, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA: Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax. 2002, 57: 759-764. 10.1136/thorax.57.9.759.View ArticlePubMedPubMed CentralGoogle Scholar
- Quint JK, Baghai-Ravary R, Donaldson GC, Wedzicha JA: Relationship between depression and exacerbations in COPD. Eur Respir J. 2008, 32: 53-60. 10.1183/09031936.00120107.View ArticlePubMedGoogle Scholar
- Baghai-Ravary R, Quint JK, Goldring JJ, Hurst JR, Donaldson GC, Wedzicha JA: Determinants and impact of fatigue in patients with chronic obstructive pulmonary disease. Respir Med. 2009, 103: 216-223. 10.1016/j.rmed.2008.09.022.View ArticlePubMedGoogle Scholar
- Cote CG, Dordelly LJ, Celli BR: Impact of COPD exacerbations on patient-centered outcomes. Chest. 2007, 131: 696-704. 10.1378/chest.06-1610.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2466/14/98/prepub
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