This study showed that both CAT and CCQ exhibit excellent reliability, good discriminate validity and high reproducibility. Both questionnaires can be used as easy and reliable tools to assess health status in COPD patients in studies as well as in daily clinical practice. Patients however preferred the CCQ since it reflected their health status better than the CAT.
The most widely used questionnaire for measuring health status in COPD in a research setting is the SGRQ. The main disadvantage for clinical practice is it’s extent as it comprises 50 questions and scores can only be calculated using a computer-based scoring system. This is in accordance with the patient’s views that perceived the SGRQ as rather complicated and time consuming. Daudey et al. based on empirical data proposed that SGRQ is not able to provide a detailed measurement of health status giving information mainly only in subjective symptoms and impairment [
18].
The CAT and CCQ were designed to measure health status in COPD patients in clinical practice and are much shorter and easy to understand. Both can be instantly calculated. Indeed patients in our study found that both are pretty easy and reflect well their status. The response option of CCQ was more clear for patients than the CAT rank system and patients thought that CCQ better reflects their health status. An advantage of CCQ is that it has been validated to be used in individual patients [
19]. In the above study patients were asked to fill in the CCQ and their results were compared to the opinion of clinicians who had seen the transcripts of an in depth interview with the same patients. The CCQ outcome of patients and clinicians was similar, supporting the individual validity.
The agreement between the questionnaire scores as reflected using Bland and Altman plot is high. The CCQ scores are generally lower at the higher end of the scales. For the comparison of the questionnaires, the scores had to be adjusted to a score of 100. The CCQ scores were multiplied by 16.67 for that purpose. A small difference in score magnifies using this calculation method. For the interpretation of the results, calculating the difference to the original scale reveals that the differences can hardly be considered clinical relevant. For example, a CAT score of 13 (median CAT score in this study) shows a difference in adjCCQ of 2.82. This represents a difference in original CCQ score of 0.17 or CAT score of 1.13. These findings are in line with previous SGRQ/CATcomparisons [
20].
Our study showed that CAT and CCQ are both reliable questionnaires in terms of internal consistency for measuring health status in COPD patients. Their high Cronbach’s alpha (α

=

0.86 for CAT and α

=

0.89 for CCQ) indicate that there is homogeneity among the individual items in the questionnaires.
In terms of discriminant validity both CAT and CCQ showed a tendency to reflect the differences in COPD severity. Patients with more severe stages of COPD reported worse health status, measured with both CAT and CCQ similarly to other studies [
21,
22]. This is true for both severity scales GOLD and BODE used in this study. In order to examine if there is a type-1 statistical error, because of the small numbers in stages I & IV, we compared CAT and CCQ scores in COPD patients GOLD stage I & II subgroup with those of stages III & IV (data not shown). Although the statistical significance difference in these comparisons remains larger studies are needed to confirm these observations. Even though FEV1 was associated with health status in this study, correlations were only weak to modest. This was expected as the pulmonary function itself measured by FEV1, on which the GOLD classification of COPD stage is based, is not a good predictor of health status [
4]. These results are in keeping with findings in previous studies (CCQ; rho

=

−0.49 and rho

=

−0.57, CAT; rho

=

−0.23) [
9,
21,
22].
Our study is the first study that assessed the variation of all three questionnaires in BODE quartiles. The BODE-index is a grading system developed to predict mortality in COPD [
15]. We found a great variation of health status in each BODE-quartile and surprisingly patients in the 3rd BODE-quartile reported worse health status as assessed with all questionnaires CAT, CCQ, SGRQ than patients in the 4th quartile. An explanation is that patients might adjust their lifestyle when the disease progresses and have therefore fewer activities that provoke dyspnea than patients with less severe disease. However other studies with appropriate design could answer this important question.
SGRQ and CCQ total scores showed good correlation (rho

=

0.769, Table ) highly indicative of convergent validity. CAT score showed a slightly weaker correlation with SGRQ (rho

=

0.646). It is lower than this reported in the study of Jones et al. [
10]. The discrepancy of lower correlation between SGRQ and CAT presented in our study could be due to different COPD population studied in terms of severity, gender and nationality. CCQ total score and CAT score also have a strong correlation (rho

=

0.644; p

<

0.01) supporting the theory that they measure the same construct. However, further studies are needed, including different clinical settings, to confirm the exact magnitude of correlation of CAT with the older quality of life instruments such as the CCQ and the SGRQ.
CAT is a one-dimensional questionnaire and it is very easy in calculation algorithm. In contrast CCQ has more similarities with SGRQ. As the SGRQ the CCQ has a division in domains. In the present study CCQ domains showed a good correlation with the respective SGRQ domains. The advantage of domains is that individual management plans can not only be specified according to the impairment of health status in general but also to the individual domains. A patient with for example an impaired mental state might be managed different from a patient with an impaired functional status. The validity of the CCQ domains is supported by our results that showed that the functional domain of the CCQ correlated significantly with the activity domain of the SGRQ (rho

=

0.753; p

<

0.01). The Bland and Altman plot (Figure) shows this high correlation, while the functional status measured by the CCQ is consistently lower than with the SGRQ.
Longitudinal validity
Overall, health status scores in subjects followed for almost 6

weeks revealed no changes over time. The CAT and CCQ both showed high test-retest reliability, ICC of the CAT was 0.94 and ICC of the CCQ was 0.95 respectively proving that they are both stable over time and supporting their validity to be used in individuals. This study reproduced the results of previous studies, where CAT and CCQ showed a similar high ICC (0.8; CAT) [
10] and (0.91-0.99; CCQ) [
9,
22,
23].
The Minimal Clinically Important Difference of the SGRQ is 4 points [
24,
25], while the MCID for the CAT has not been established officially but was estimated to be around 2 points [
26,
27]. The MCID of the CCQ has previously been calculated based on three methods and is 0.4 [
28]. In our study we were unable to use distribution-based methods to determine and compare the MCID of the three questionnaires. We compared changes in patient reported outcomes scores to measures of variability. The MCID calculated with the SEM of the CCQ and SGRQ is somewhat similar to the MCID’s found in previous studies. The estimated MCID of the CAT, however, was higher 3.76 points. Hence, further studies are needed to determine the MCID of this relatively new tool.
Strengths and limitations of the study
This is a real life study, the first that did a head to head comparison of CAT, CCQ and SGRQ in three continuous visits. Several other factors were also examined as spirometry, dyspnea, 6MWT and BODE index. This study has some limitations that should be reported. Firstly this study has been limited to one country and performed in one centre. Since no intervention was included many patients showed to be stable over time. This resulted in an unchanged health status making it impossible to calculate the MCID with anchor based methods and to compare the questionnaires responsiveness. Further this study was not designed to see if the CAT and CCQ both reflected indeed all the COPD patient’s relevant aspects. Larger studies with different design could answer this very important issue.