Приложение на САТ-теста при ХОББ в екзацербация

Usefulness of the Chronic Obstructive Pulmonary Disease Assessment Test to Evaluate Severity of COPD Exacerbations


Alex J. Mackay1, Gavin C. Donaldson1, Anant R. C. Patel1, Paul W. Jones2, John R. Hurst1, and Jadwiga A. Wedzicha1
1Academic Unit of Respiratory Medicine, University College London Medical School, Royal Free Campus, London, United Kingdom; and 2Division of Clinical Science, St George’s University of London, London, United Kingdom



Rationale: The Chronic Obstructive Pulmonary Disease (COPD) AssessmentTest(CAT)isaneight-itemquestionnairedesignedtoassess and quantify the impact of COPD symptoms on health status. COPD exacerbations impair quality of life and arecharacterized by worsening respiratory symptoms from thestablestate. We hypothesized that CAT scores at exacerbation relate to exacerbation severity as measured by exacerbation duration, lung function impairment, and systemic inflammation. Objectives:To evaluate the usefulness of the CAT to assess exacerbation severity.

Methods: Onehundredsixty-onepatientsenrolledintheLondonCOPD cohortcompletedthe CATat baseline (stablestate),exacerbation, and during recovery between April 2010 and June2011. Measurements and Main Results: Frequent exacerbators had significantly higher baseline CAT scores than infrequent exacerbators (19.5 6 6.6 vs. 16.8 6 8.0, P ¼ 0.025). In 152 exacerbations, CAT scores rose from an average baseline value of 19.4 6 6.8 to 24.1 6
7.3 (P , 0.001) at exacerbation. Change in CAT score from baseline to exacerbation onsetwassignificantlybutweaklyrelated tochange in C-reactive protein (rho ¼ 0.26, P ¼ 0.008) but not to change in fibrinogen (rho ¼ 0.09, P ¼ 0.351) from baseline toexacerbation. At exacerbation, rises in CAT score were significantly associated with fallsinFEV1(rho¼ 20.20,P ¼ 0.032).Medianrecoverytimeasjudged by symptom diary cards was significantly related to the time taken for the CAT score to return tobaseline (rho ¼ 0.42, P ¼ 0.012). Conclusions: The CAT provides a reliable score of exacerbation severity. Baseline CAT scores are elevated in frequent exacerbators. CAT scoresincreaseatexacerbationandreflectseverityasdeterminedby lung function andexacerbation duration.
Keywords: chronic obstructive pulmonary disease; exacerbations; severity; patient-reported outcomes; symptoms


Scientific Knowledge on the Subject
Currently there is no standardized, objective method for assessing symptom severity at exacerbation of chronic obstructive pulmonary disease (COPD) that has been universally accepted and available for use in both routine clinical practice andclinical trials.
What This Study Adds to the Field
The COPD Assessment Test (CAT) provides a reliable score of exacerbation severity, and its incorporation into assessment strategies may aid healthcare professionals to determine the severity of exacerbations and potentially assist management.The CAT may also prove useful in clinical trials to objectively assess the ability of novel interventions to reduce exacerbation severity.



Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway condition associated with episodes of acute deterioration termed exacerbations (1). Exacerbations are among the commonest causes of medical admission to the hospital (2), and the rate at which they occur appears to reflect an independent susceptibility phenotype (3). They are also important events in the natural history of COPD that drive lung functiondecline (4, 5), increase risk of cardiovascular events (6), and are responsible for much of the morbidity (7) and mortality (8) associated with this highly prevalent condition.
COPD exacerbations are characterized by a worsening of respiratory symptoms from the usual stable state, especially dyspnea, increased sputum volume, and purulence. Changes in exacerbation symptoms relate to exacerbation recovery time(9), which is an index of exacerbation severity. In addition to exacerbation length, exacerbation severity influences acute treatment (9) and drives hospital admission and mortality (8).
Patient diary cards are direct measures of exacerbation symptoms that provide accurate information regarding the commencement and resolution of exacerbations (9). They can detect exacerbations that are both reported and unreported tohealthcare professionals, thus allowing accurate determination of exacerbation frequency (7). However, currently there is no standardized, objective method for assessing symptom severity at exacerbation that has been universally accepted andavailable for use in both routine clinical practice and clinical trials.
The COPD Assessment Test (CAT) is a validated eight-item questionnaire designed to assess and quantify the impact of COPD symptoms on patient health status (Figure 1). It has excellent measurement properties (10) and is short andsimple for patients to complete, providing a score out of 40 to indicate disease impact, without the need for complex calculation. Initial studies have shown that the CAT correlates closely with health-related quality of life as measured by the St.George’s Respiratory Questionnaire (SGRQ) when patients are stable (10), and it is responsive to pulmonary rehabilitation (11).
We hypothesized that elevated CAT scores at COPD exacerbation relate to exacerbation severity as measured by exacerbation length, lung function impairment, and systemic inflammation. Furthermore, we hypothesized that CAT scores canbe used to model recovery. Therefore, well-characterized patients were prospectively assessed using the CAT in the baseline stable state, at exacerbation presentation, and thereafter for 5 weeks during the recovery period.


Figure 1. Chronic Obstructive Pulmonary Dis¬ease (COPD) Assessment Test (CAT). Reprinted by permission from GlaxoSmithKline.


Patient Recruitment
This study involved 161 patients with COPD enrolled in the London COPD cohort between January 1, 2009 and June 1, 2011. The patients form part of a rolling cohort used to prospectively investigate the mechanisms of COPD exacerbations. Patientswere included if the postbronchodilator FEV1 was less than or equal to 80% predicted from age, height, and sex, and FEV1/FVC ratio was less than 0.7 (12). Patients with a history of any other significant respiratory diseases were excluded, as were thoseunable to complete daily diary cards.
At annual review or recruitment, a full medical and smoking history was obtained, a clinical examination performed, and the SGRQ (13) completed. Comorbid diagnoses were established using clinical history and examination findings during a stable-statevisit, supported where appropriate with a review of available medical records. FEV1 and FVC were measured with a Vitalograph Gold Standard spirometer (Vitalograph Ltd., Maids Moreton, UK). Oxygen saturations were also measured (PureSAT; NoninMedical Inc., Plymouth, MN). Body mass index (BMI) was calculated from height and weight.
Ethical approval for the study was granted from the Royal Free Hospital research ethics committee, and all patients gave written informed consent. Permission to use the CAT questionnaire was obtained from GlaxoSmithKline. The recruitment andmonitoring of these patients has been previously described, and the cohort has been the subject of previous publications (7, 9, 14–16), but the current study is entirely novel and has not been reported before.
Monitoring and Definition of Exacerbations
Patients were asked to record daily peak expiratory flow rate (PEFR) measured with a mini-Wright meter (Clement-Clark International, Harlow, UK), hours spent outside the home, and any increase in respiratory symptoms on diary cards. An exacerbationwas defined as an increase for two consecutive days in respiratory symptoms, with at least one major symptom (dyspnea, sputum purulence, or sputum volume) plus either another major or a minor symptom (wheeze, cold, sore throat, and cough), the firstof which was defined as the day of onset of the exacerbation. Symptom counts were obtained by summating each increased respiratory symptom recorded on diary cards per day.
Exacerbation duration was defined as the number of days after onset that worsening symptoms persisted. The last day of recorded worsening symptoms before two consecutive symptom-free days defined the end of the exacerbation. Exacerbationrecovery was not determinable if patients failed to record diary card symptoms or continuously recorded symptoms for more than 99 days after onset. Exacerbation frequency was calculated for each patient using diary card data obtained between January2009 and June 2011. For recently recruited patients with less than 1 year diary data, exacerbation frequency was based on the number of exacerbations the patient recalled for the year before recruitment. Previous work has shown a good correlationbetween the number of exacerbations recorded on diary cards and the number of exacerbations remembered by the patient over the same 1-year period (17) and has shown that exacerbation frequency represents a stable patient phenotype (3).
Exacerbation Assessment
Exacerbations were treated according to the prevailing guidelines and clinical judgment with increased inhaled therapy, antibiotics, and/or oral steroids. Neither the magnitude of exacerbation CAT score nor the diary card symptom score played any role intreatment decisions. When patients attended for an exacerbation, venous blood samples were taken and spirometry performed before commencing exacerbation treatment. Serum C-reactive protein (CRP) was measured using Modular Analytics E 170Module (Roche, Burgess Hill, UK) and plasma fibrinogen using the Clauss method (IL ACL Top Coagulation Analyzer; Lexington, MA).
CAT Administration
Patients completed the CAT at least once under supervision in clinic and then at home, based on their symptoms experienced on the day of completion. Patients completed at least one CAT questionnaire in the stable, baseline state. Baseline occurredmore than 35 days after and 21 days before exacerbation onset. If unavailable before index exacerbation, CAT scores during periods of stability postexacerbation were used to provide a baseline. No differences were seen between baseline scores obtainedpreindex exacerbation and baseline scores postexacerbation. Repeat scores were averaged to give a baseline CAT score. CAT questionnaires were also administered during exacerbation between April 2010 and June 2011. The exacerbation CAT score tookplace within 7 days of the symptomatic onset of the exacerbation as judged by diary cards, was completed before starting therapy, and was recorded on the day treatment commenced. These were mandatory study criteria.
A subgroup of patients also completed CAT scores on a daily basis during their recovery. For the recovery subgroup, the first exacerbation was selected for analysis provided the patient had fully completed the questionnaire on at least 21 of 35 dayspost onset. CAT Recovery was the time taken from exacerbation onset for the CAT score to return to baseline value (see Figure E1 in the online supplement).
Statistical Analysis
Data were analyzed with STATA 8.2 (Stata Corporation, College Station, TX). Normally distributed data were expressed as mean and standard deviation (SD) and skewed data as median and interquartile range (IQR). Comparisons were made by pairedStudent t test or Wilcoxon signed-rank test. The relationship between exacerbation frequency and baseline CAT scores was examined with a negative binomial regression model, whereas Poisson regression was used to model exacerbation recovery and CATscores. Cross-sectional regression models were used to analyze the relationship between inflammatory markers during exacerbation and CAT score as allowance could be made for repeated measures on the same patient.
Patient Characteristics
One hundred sixty-one patients with COPD completed at least one CAT questionnaire when stable (exacerbation free). Their baseline characteristics are reported in Table 1 alongside 75 patients who were assessed using the CAT at exacerbationand the 52 of these who completed the CAT questionnaire daily during exacerbation recovery. The patients had moderate to severe disease with a mean FEV1 % predicted of 50.3% (range, 14.0–79.7%). Patients in whom CAT was assessed atexacerbation had significantly higher exacerbation frequencies (P , 0.001) but differed in no other respect.
Patients completed the CAT successfully when stable and when acutely unwell during an exacerbation. In total, 6,404 out of 6,514 questionnaires (98.3%) were completed fully. There was no significant difference in the percentages fullycompleted at baseline, 3,496 of 3,561 (98.2%), compared with those at exacerbation onset and during recovery, 2,908 of 2,953 (98.5%, P ¼ 0.35).
Use of CAT at Baseline
Baseline CAT and exacerbation frequency. The 161 patients had a mean baseline CAT score of 18.1 (SD, 7.45). Frequent exacerbators (>2 exacerbations per year, n ¼ 80) had a mean CAT score of 19.5 (SD, 6.6) compared with infrequentexacerbators (,2 exacerbations per year, n ¼ 81), whose mean CAT score was 16.8 (SD, 8.0; P ¼ 0.025; Figure 2). Thus, there was an average 2.7-point difference in CAT score between the frequent and infrequent exacerbators.
Relationship between CAT score and systemic inflammatory markers in the baseline state. At baseline, serum CRP was measured on the same day as a CAT was completed in 318 blood samples obtained from 150 separate patients and plasmafibrinogen in 282 blood samples from 144 patients. There was a significant relationship between systemic inflammation, as measured by log10 fibrinogen, and CAT score on the day of baseline sampling, regression coefficient ¼ 0.0014 (95% CI,0.0001–0.0027; P ¼ 0.035; Figure 3), R2 ¼ 0.024 using random-effects generalized least squares regression. However, there was no statistically significant relationship between log10 CRP and CAT scores, regression coefficient ¼ 0.0059 (95% CI,20.0016 to 0.0133; P ¼ 0.122).
No difference in baseline CAT scores was seen between patients with or without potentially confounding comorbidities (congestive heart failure, renal failure, obesity, or sleep-disordered breathing; Table 2), confirming previous work thatCAT scores appear unaffected by low levels of comorbidity (18).
Use of CAT at Exacerbation
The CAT was completed at 152 treated exacerbations by 75 patients. The median interval from diary card exacerbation onset to the day of treatment was 2 days (IQR, 1–4). Figure 4 shows that the CAT score rose from an average baseline valueof 19.4 (SD, 6.8) to 24.1 (SD, 7.3; P , 0.001) at exacerbation.
The magnitude in rise of CAT score from baseline to exacerbation was not affected by patient baseline characteristics. Patients whose change in CAT score at exacerbation was on average greater or equal to 2 units displayed no significant difference in age (73.2 vs. 70.3 yr, P ¼ 0.13), FEV1% predicted
(47.6 vs. 47.3%, P ¼ 0.94), or exacerbation frequency (2.73 vs. 2.48, P ¼ 0.586) from those with smaller changes in CAT score.


The symptomatic characteristics of exacerbations did not significantly affect the magnitude of CAT rise at exacerbation (see online supplement). Although patients within the London COPD cohort complete daily symptom diary cards, whichallows detection of exacerbations that are unreported to health-care professionals and untreated with extra medication (7), all 152 exacerbations included in the analyses were treated. The vast majority of exacerbations were treated with systemictreatment after clinical review by a member of the research team; 103 exacerbations were treated with antibiotics and oral corticosteroids, 22 with antibiotics alone, and 7 with oral steroids alone. Just 20 patients increased inhaled therapy(bronchodilators and/ or inhaled corticosteroids) alone without systemic treatment. Increases of more than 2 units in CAT score were associated with a greater likelihood of treatment with antibiotics (88.7 vs. 70.4%, P ¼ 0.004) but not oralsteroids (75.5 vs. 66.7%, P ¼ 0.243).
The main analysis was repeated using a strict healthcare use definition of an exacerbation, based on physician review and increased systemic treatment. One hundred thirty-two exacerbations fitted this criterion. The mean change in CAT scorefrom baseline to healthcare use exacerbation was 5.2 units (SD, 6.7; n ¼ 132). Mean change in CAT score from baseline to exacerbation for patients who received increased inhaled therapy alone was 2.0 (4.9), although this was based on just 20exacerbations. Further work is required to further explore the relationships between changes in CAT at exacerbation and choice of exacerbation treatment.
Relationship between CAT score and systemic inflammatory markers at exacerbation. CAT scores at exacerbation were significantly related to concurrent levels of systemic inflammatory markers. At exacerbation, serum CRP was measured onthe same day as a CAT was completed in 114 exacerbations and plasma fibrinogen in 111 exacerbations. After log10 transformation, both inflammatory markers were significantly related to the CAT score recorded at exacerbation, and withallowance for repeated measures in the same patient, log10 CRP increased by 0.028 (95% CI, 0.013–0.043; P , 0.001) and log10 fibrinogen by 0.003 (95% CI, 0.001–0.005; P ¼ 0.015), per unit increase in CAT score. Change in CAT score from baseline to exacerbation onset was significantly related to change in CRP (rho ¼ 0.26, P ¼ 0.008) but not to change in fibrinogen (rho ¼ 0.09, P ¼ 0.351) from baseline to exacerbation.



Lung function changes and CAT scores at exacerbation. CAT scores were significantly related to contemporaneous spirometry, as measured by FEV1. At exacerbation, spirometry was performed on the same day as a CAT was completed in112 exacerbations. Mean paired FEV1 measured at baseline was 1.12 L (SD, 0.44) and 1.01 L at exacerbation (SD, 0.44; P , 0.001). Rises in the CAT score recorded at exacerbation were significantly associated with falls in FEV1 at exacerbation(rho ¼ 20.20, P ¼ 0.032).
Time Course of CAT Scores during Exacerbation Recovery
Fifty-two different patients completed the CAT questionnaire on at least 21 of 35 days during the recovery phase after an exacerbation. All of these 52 exacerbations were treated: 41 with antibiotics and oral steroids, 5 with antibiotics alone, 3with oral steroids alone, and 3 with increased inhaled therapy alone. Figure 5 shows the time course of the CAT scores, PEFR, and diary card symptom counts (further details are available in the online supplement).
Relationship between CAT score and symptom recovery. CAT scores reflected symptomatic recovery after exacerbations. Among the52episodes, themedianrecoverytimeasjudged by symptom diary cards was 12 days (IQR, 9–23; n ¼ 47),and this was significantly related (rho ¼ 0.42, P ¼ 0.012) to the time taken for the CAT score to return to baseline (median, 11 d; IQR, 4.5–17; n ¼ 40).
This novel study prospectively assessed the usefulness of the CAT to evaluate exacerbation severity in patients with COPD. At exacerbation, CAT scores were significantly elevated from paired baseline values, and we have uniquelydemonstrated that CAT scores reflect exacerbation severity as measured by exacerbation length and reduction in lung function. A weak relationship was also found between systemic inflammatory markers and CAT scores at exacerbation.Furthermore, we have shown that baseline CAT scores are significantly elevated in patients with stable COPD with a history of frequent exacerbations.
The CAT is a validated health status questionnaire that is free to use and can be administered without prior permission for research purposes and by individual practitioners (http://www.catestonline. org ). Previous studies have shown thatthe instrument can be successfully administered in both primary (18) and secondary care settings (11) and is responsive to a course of pulmonary rehabilitation and able to distinguish different levels of response (11). Additionally, CAT scoresexhibit little variability across countries; they are not influenced by age or sex but reflect disease severity in the stable state as determined by Global Initiative for Chronic Obstructive Lung Disease spirometric staging, Medical Research Councildyspnea score, SGRQ, and clinician-judged severity (10, 18).
Our study complements this existing work by demonstrating that the CAT can be used as a score of the multidimensional nature of COPD exacerbation severity. At present, the assessment of symptom severity at exacerbation and duringrecovery is subjective in nature, with no established scoring system in clinical practice. Exacerbation therapy is currently determined by a subjective physician assessment of exacerbation severity, and so an objective tool to determine exacerbationseverity will fulfill an important unmet need. This has particular relevance as patients are increasingly seen by healthcare professionals in the community, often within their own homes, without the benefit of objective measures of exacerbationseverity such as accurate spirometry or systemic inflammatory markers. PEFR is a cheap, reliable, and easy way for patients to assess lung function on a daily basis. We have shown in previous studies that PEFR decreases to a small extent butsignificantly at exacerbation onset and can be a useful tool to indicate exacerbation recovery in population studies. However, the changes are not large enough to use PEFR at an individual level for exacerbation detection and monitoring (9).
An objective, validated exacerbation severity score is also required for use in clinical trials. Treatments to prevent exacerbations may also reduce exacerbation severity in addition to exacerbation frequency, but at present tools to determineefficacy of this are limited, and only exacerbation rates are usually recorded in clinical studies (19, 20). Most clinical trials to date have used therapy and hospitalization rates to assess exacerbation severity, and thus an objective symptom severityscore will enable the ability of novel interventions to reduce exacerbation severity to be assessed and compared across studies (21). Therapies involving either exacerbation prevention or management of the acute exacerbations may reduceexacerbation CAT scores or the time taken for scores to recover to baseline. Further evaluation of the CAT in clinical trials is now required.
The CAT provides an objective quantification of the impact of symptoms that is acceptable to patients and can be easily completed at exacerbation and during recovery. We have previously shown that systemic inflammation, as measured byplasma fibrinogen and serum CRP, increases at exacerbation (22–24), and in this study we have demonstrated a weak relationship between CAT scores at exacerbation and systemic inflammatory markers. Inflammatory changes at COPDexacerbations are also related to clinical nonrecovery and recurrent exacerbations within 50 days (15). Recovery time is an index of exacerbation severity (9), and for the first time this study has evaluated use of the CAT during exacerbationrecovery. We have demonstrated that CAT scores reflect recovery after exacerbations, the time taken for scores to return to baseline being significantly related to recovery time as judged by symptom diary cards. Additionally, at exacerbation,CAT scores are significantly but modestly related to contemporaneous lung function impairment, as measured by FEV1,consistent with previous data examining the relationship between baseline CAT scores and FEV1 (18). Thus, CAT scoresprovide an easily quantifiable overall score of exacerbation severity and may be useful in studies evaluating interventions for the management of acute exacerbations.


Figure 4. Mean Chronic Obstructive Pulmonary Disease Assessment Test (CAT) scores at baseline and exacerbation for 152 exacerbations (75 patients). Vertical lines represent SEs.




Figure 5. Time course of Chronic Obstructive Pulmonary Disease Assessment Test (CAT) scores, peak expiratory flow rate, and diary card symptom counts during exacerbation recovery (52 patients). Vertical bars represent SEs. Horizontal lines indicate mean baseline scores.


When measured in the stable state, CAT scores are highly correlated to concurrent SGRQ measurements (10). However, this study has shown a divergence between the behavior of the CAT and SGRQ during exacerbation recovery. After astudy of exacerbations of chronic bronchitis, although an early improvement is seen in SGRQ scores when measured 4 weeks after an index event, improvements can also slowly continue for several months (25). In this study we found that CATscores have returned to baseline levels more rapidly. This may be a result of the daily use of the instrument in this study and the response system in the CAT, which is based on categories of difference between two extreme statements about thesame COPD impact. In contrast, the SGRQ has predominantly dichotomous yes/no responses and is administered at intervals. Thus, although we have demonstrated that the CAT can reliably assess exacerbation severity, daily CAT readingsmay overestimate the speed of recovery of health status postexacerbation.
This study has also added to previous data examining the use of the CAT in the baseline stable state by examining the relationship between baseline CAT scores and exacerbation frequency. Patients with a history of frequent exacerbationshave worse quality of life (7), increased risk of hospitalization (26), and greater mortality (8). Frequent exacerbators also exhibit faster decline in lung function (4) and may have worse functional status, as measured by time outdoors (16). In thisstudy we have shown that baseline CAT scores relate to exacerbation frequency. When used in the stable state, scores were significantly elevated in frequent exacerbators, defined by two or more exacerbations per year, compared with infrequentexacerbators. Also, baseline CAT scores were weakly but significantly related to concurrent fibrinogen levels. We have previously shown that plasma fibrinogen levels are elevated in patients with stable COPD (23) and that increased systemicinflammation, as measured by fibrinogen, in patients with stable COPD over time is directly linked to disease progression, as defined by lung function decline (27). Further work is required to explore whether CAT scores may potentially be auseful marker of disease progression over time in COPD.
Because our results indicate that CAT scores may reflect levels of systemic inflammatory markers, albeit weakly, this finding may have particular relevance in clinical trials of antiinflammatory therapeutic agents in COPD. The effects ofantiinflammatory therapies aredifficult toassess as changes in FEV1 tend to be small (28), and exacerbation frequency as an outcome has to be assessed over at least a 12-month period. Further study is now required of CAT scores duringantiinflammatory interventions in COPD.
The Exacerbations of Chronic Pulmonary Disease Tool (EXACT) is a patient-reported outcome diary specifically designed to quantify the frequency, severity, and duration of exacerbations of COPD in clinical trials (21). EXACT scores havebeen shown to differentiate patients who were stable from patients with mild and moderate exacerbations as judged by clinicians (21). However, to date no published data have demonstrated the relationship of EXACT scores to levels of systemicinflammation and lung function changes seen at exacerbation and during recovery. Furthermore, in published papers thus far, the EXACT has been used in conjunction with a personal digital assistant (21, 29) or Blackberry smartphone (30),potentially limiting its widespread uptake in routine clinical practice.
We have shown that the CAT is a potentially useful, widely applicable tool that can aid assessment of exacerbation severity. The CAT can be easily and rapidly completed in many health-care settings and could potentially be integrated intocare bundles of patients with COPD without additional cost. Patient recognition of exacerbation symptoms and prompt treatment improves exacerbation recovery and reduces the risk of hospitalization in patients with COPD (31). Furtherevaluation is now required of the CAT within exacerbation management strategies to assess usefulness of the tool within clinical practice.
In conclusion, the CAT provides a reliable score of exacerbation severity. CAT scores increase at exacerbation and reflect exacerbation severity as determined by lung function and exacerbation length. A weak relationship was also foundbetween systemic inflammatory markers and CAT scores at exacerbation. Thus, the CAT is a valuable instrument to enhance and standardize COPD exacerbation assessment. Incorporating this questionnaire into assessment strategies may aidhealthcare professionals to determine the severity of exacerbations, particularly in situations where access to other objective measures of severity is limited. The CAT may also prove useful in clinical trials to objectively assess the ability of novelinterventions to reduce exacerbation severity.
Author disclosures areavailable withthetext ofthisarticleat www.atsjournals.org .
Acknowledgment: The authors thank Beverly Kowlessar (research nurse) for her helpin CAT administrationand collection. They also thankGilbert Nadeau(Glaxo-SmithKline) for facilitating use of the CAT in this study.


(Received in original form October 17, 2011; accepted in final form January 11, 2012)
Author Contributions: Study idea and design: A.J.M., G.C.D., J.A.W. Analysis and interpretationof results: A.J.M., G.C.D.,A.R.C.P., P.W.J., J.R.H., J.A.W.Manuscript drafting/revision: A.J.M., G.C.D., A.R.C.P., P.W.J., J.R.H., J.A.W.
The London COPD cohort is funded by the MRC Patient Research Cohort Initiative. This work was supported by an unrestricted educational grant from Glaxo-SmithKline.
Correspondence and requests for reprints shouldbeaddressedtoAlexJ.Mackay, M.B.B.S., Academic Unit of Respiratory Medicine, University College London Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, United Kingdom. E-mail: alexander.mackay@ucl.ac.uk
This article has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org
Am J Respir Crit Care Med Vol 185, Iss. 11, pp 1218–1224, Jun 1, 2012 Copyright ª 2012 by the American Thoracic Society Originally Published in Press as DOI: 10.1164/rccm.201110-1843OC on January 26, 2012 Internet address: www.atsjournals.org

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