Usefulness of the LCOPD, CAFS and CASIS Scales in Understanding the Impact of COPD on Patients

Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality worldwide [1] and has a very significant impact on patients' quality of life [2]. This is one of the main reasons why interest in outcomes centered on the patients and their experience with COPD has grown exponentially in recent years [3,4].

There is an abundance of research on describing and gathering knowledge about the impact of COPD on daily life, and also on the impact of different therapeutic approaches [5,6]. Specific instruments for COPD have been used, such as the St. George's Respiratory Questionnaire [7], as well as generic instruments such as the EuroQoL 5D [8,9] or a combination of both [10]. Other research has explored the relationship between COPD and mood, quantifying the presence of symptoms of anxiety or depression in specific populations of patients with COPD and/or perceiving how mood can influence tolerance to physical exercise, social isolation, or the likelihood of rehospitalization [11,12] by employing instruments such as the Hospital Anxiety and Depression Scale [13,14]. The relationship between COPD and physical and functional capacity has also been a focus of research [15,16] with the recent availability of the London Chest Activity of Daily Living scale [17], the validated Spanish version of which was published lately [18].

However, although there is evidence that fatigue and sleep impairment are frequent problems in patients with COPD [19,20,21], there is little available to help quantify these important aspects. Until very recently there were no suitable instruments considered validated for use within the COPD population. For this reason, two specific instruments have recently been developed and validated for patients with COPD: the COPD and Asthma Fatigue Scale (CAFS) [22] and the COPD and Asthma Sleep Impact Scale (CASIS) [23]. The Living with COPD (LCOPD) questionnaire is a new instrument that measures the overall impact of COPD on daily life [24]. The objectives of the current study were to assess the usefulness of these new instruments and to identify factors associated with the concepts they measure.

This was an observational cross-sectional, descriptive, and multicenter study carried out in pneumology departments of 21 hospitals in Spain.

Included patients had to meet the following criteria: (a) diagnosis of moderate or severe COPD (determined by spirometry after a bronchodilator test with an FEV₁/FVC <0.70 and FEV₁ <80%, undergone within 6 months prior to inclusion into the study); (b) age ≥40 years; (c) smokers or ex-smokers of at least 10 pack-years; (d) with COPD for at least 5 years; (e) attended a scheduled follow-up appointment according to usual clinical practice; (f) had signed the informed consent form, and (g) were capable of understanding and completing the questionnaires that would be administered.

Patients not included in the study were those who: (a) presented with an acute exacerbation of COPD at the time of inclusion or had presented with an exacerbation within 8 weeks prior to inclusion; (b) presented with an exacerbation of other concomitant diseases; (c) had a diagnosis of asthma or pneumonia; (d) were already participating in a clinical trial or research study, or (e) were on home oxygen therapy.

The study sample size was calculated for each of the LCOPD, CASIS, and CAFS scales, with a statistical significance level of 5%, a power of 90%, an accuracy of ±2 points, and assuming that 10% of the information gathered from patients would not be valid or analyzable. The greatest necessary sample size was determined by the CASIS scale, estimated at 419 cases, with a typical deviation of 19.8, obtained according to the scale validation [23].

The study was approved by the Ethics Committee of the Hospital Clínic of Barcelona and all patients signed an informed consent form to participate.

Sociodemographic data (age, gender, and level of education), clinical data related to COPD: time elapsed since diagnosis, smoking habits, pulmonary function, clinical symptoms of COPD, treatment(s) received, and exacerbations suffered in the previous 12 months were gathered for each patient. The degree of dyspnea was assessed by means of the Medical Research Council scale [25].

The overall impact of COPD on daily life was assessed using the validated Spanish version of the LCOPD [26]. The LCOPD consists of 22 items that identify a wide range of situations where COPD could negatively impact daily life. An overall score is obtained ranging from 0 to 22, where high scores indicate a major impact of COPD on daily life [24].

Fatigue associated with COPD was assessed by means of the validated Spanish version of the CAFS [27]. The CAFS is a questionnaire created to assess fatigue associated with COPD and asthma. The questionnaire consists of 12 items that explore the frequency with which certain situations and symptoms associated with tiredness and fatigue arise. A global score is obtained ranging from 0 to 100, where high scores indicate a major impact of COPD on the patient's fatigue [22].

The impact of COPD on sleep was assessed by means of the validated Spanish version of the CASIS [28]. The CASIS is a questionnaire developed to assess sleep-related problems and disorders associated with COPD and asthma. The questionnaire consists of 13 items that explore the frequency with which certain situations and symptoms associated with sleep-related problems arise. An overall score is obtained ranging from 0 to 100, where high scores indicate a major impact of the COPD on the patient's sleep [23].

The physical activity level was gathered by means of the validated Spanish version of the London Chest Activity of Daily Living scale (LCADL) questionnaire [18]. The LCADL is a questionnaire developed to assess the physical activity level and functional autonomy of respiratory care patients. It consists of 15 items distributed in 4 dimensions (‘basic self-care tasks', ‘domestic tasks', ‘physical activities', and ‘leisure/free time') as well as an additional independent item concerning the limitations associated with the patient's breathing. An overall score and a summary score are obtained for each dimension, where high scores indicate a major impact of COPD on the patient's physical activity [17].

Detection of anxiety states and depression was performed using the Spanish version of the Hospital Anxiety and Depression Scale (HADS) questionnaire [29]. The theoretical intervals of both dimensions (anxiety and depression) range from 0 to 21, where high scores indicate major levels of anxiety and depression. A score of 8 or higher identifies the probable presence of anxiety or depression [30].

The categorical variables were described as the number and percentage of subjects in each category and the continuous variables as means and SD. Nonparametric tests were performed (Kolmogorov-Smirnov bilaterally with a confidence level of 95%) to assess the normal distribution of the questionnaire scores. Bivariate analysis was performed using nonparametric Mann-Whitney tests (for two samples) and the Kruskal-Wallis test (for n samples), both bilaterally with a confidence level of 95%, and Spearman's rho for continuous variables, as appropriate in each case.

Multivariate analysis was performed using a simple linear regression model. The purpose of this analysis was to explore and, to the greatest extent possible, identify variables associated with the impact on daily life, fatigue, and sleep impairment. p < 0.05 was considered statistically significant. Statistical analysis was performed with SPSS software, version 13.0.

A total of 431 patients were screened, 23 of whom were excluded for noncompliance with one or more of the inclusion criteria. The study population was composed of 408 patients. Table 1 presents sociodemographic and clinical characteristics. Patients were, for the most part, males (91.2%) with an average age of 68 years (SD = 9.3) and a low or very low education level (80%). The average time elapsed since the diagnosis of COPD was 11 years (SD = 6.2). The mean FEV₁ (%) post-bronchodilator was 50.3% (SD = 14.1%). Sixteen percent of the population still smoked and the average tobacco consumption was 51.9 pack-years (SD = 33). The average dyspnea level was 2.7 (SD = 0.9). The most common medications were anticholinergics (89%), long-acting β₂-agonists (87.7%), inhaled corticosteroids (85.3%), and short-acting β₂-agonists (50.7%). Of the patients, 64.3% had suffered at least 1 exacerbation in the 12 months prior to their inclusion into the study, and 20.8% had had 3 or more exacerbations.

The results obtained from the questionnaires are presented in table 2. The mean scores on the LCOPD (interval 0-22) were 8.8 (SD = 5.9) and 21 (SD = 12.8) for the LCADL scale (interval 0-75). The mean scores for the CAFS and CASIS were 35.8 (SD = 24.7) and 29.7 (SD = 22.1), respectively, and both scales had intervals of 0-100. The HADS scale results indicate that 27.2 and 22.8% of the patients had a high likelihood of suffering from anxiety disorders and depression, respectively.

Statistically significant differences were observed in the LCOPD, CAFS, and CASIS scores among patients with different clinical and demographic characteristics (table 3). The patients with worse dyspnea, a greater number of exacerbations in the previous 12 months, less physical activity assessed by means of the LCADL, and more anxiety or depression symptoms had worse scores on all of the scales analyzed (p < 0.0001). Statistically significant differences were also observed (p < 0.0001) in the LCOPD and CAFS scores depending on the presence or lack thereof of chronic cough, deterioration of FEV₁ (%), and the number of treatments received for COPD.

The LCOPD and CAFS scores significantly differed depending on the stage of COPD. The scores of the three questionnaires differed according to the degree of dyspnea and the number of exacerbations the previous year (fig. 1, 2, 3).

With regard to the correlation analysis between the questionnaire scores and clinical variables, the greatest correlation was observed between the activity score of the LCADL and CAFS (r = 0.62), LCOPD (r = 0.60), and CASIS (r = 0.44). The correlations with the MRC dyspnea scale were also noteworthy (r = 0.54, r = 0.56, and r = 0.32 for CAFS, LCOPD, and CASIS, respectively). The remaining correlations were of a lower intensity (table 4).

The results of the multivariate analysis (table 5) showed that degree of dyspnea, level of physical activity, and presence of anxiety were independently and significantly associated (p < 0.012) with the scores of the three LCOPD, CAFS, and CASIS questionnaires. In addition, for both the LCOPD and the CAFS questionnaire independent associations with other clinical variables were observed: the presence of depression in both cases and chronic cough in CAFS. The regression models showed adjustments of 52, 54.5, and 37.1% for the LCOPD, CAFS, and CASIS questionnaires, respectively.

The significance of respiratory symptoms and exercise limitation with COPD is well known and can be documented with validated questionnaires or well-established tests [12,15,31]. However, when making a complete assessment of the patient with COPD, other relevant aspects affected by the illness must be taken into account. Among these aspects relating to health-related quality of life are: overall impact of COPD, fatigue, and sleep impairment. The current study has shown that patients with moderate to severe COPD are significantly impacted in these areas.

There are generic [8] and specific questionnaires for chronic respiratory disease [5,7,32]. The LCOPD questionnaire which measures the overall impact of COPD as perceived by the patient is a validated instrument consisting of 22 items, which in addition to its good psychometric properties has the advantage of being easy and quick to complete [24]. We have established its discriminating power with respect to the severity of airflow obstruction, degree of dyspnea, presence of respiratory symptoms, and other aspects previously reported using other questionnaires, such as the frequency of exacerbations [33,34], level of education [35], physical activity [36,37], and presence of anxiety or depression [38]. The similarity in the direction of the results obtained with the LCOPD questionnaire and other specific questionnaires for COPD indicates that the LCOPD questionnaire is a simple and useful instrument to assess the impact of COPD on daily life in COPD patients.

One of the most characteristic aspects of COPD is the slow and progressive development of exercise limitation, which in the most severe cases can be disabling [16,39]. The main manifestation of airflow obstruction is exertional dyspnea, although fatigue can also play an important role. The distinction between dyspnea and fatigue is relevant, since this could imply different or complementary therapeutic approaches. In addition to respiratory causes [40], fatigue in COPD can be the result of comorbidities [41], previous exacerbations or hospitalizations [42], or peripheral muscle weakness or atrophy [40]. The need to quantify the sensation of fatigue has led to the development of questionnaires, such as the Manchester fatigue scale, consisting of 27 items distributed in three dimensions. This scale has shown its usefulness in a group of 122 patients with moderate COPD [43]. On the other hand, the CAFS questionnaire consists of only 12 items and has demonstrated excellent psychometric properties in our population of 408 patients with moderate to severe COPD. Also outstanding is its good correlation with the LCADL activity scale, the degree of dyspnea, and a limited correlation with the FEV₁ (%) post-bronchodilator. It is interesting to note how coughing has a significant and direct impact on the CAFS score. Coughing is a significant symptom that has been associated with fatigue and deterioration of the quality of life [31,44,45].

Lastly, the CASIS questionnaire has allowed us to assess the impact of COPD on sleep impairment. In our study, sleep was impaired as indicated by a mean score of 29.7 out of 100, but with a large dispersion of scores. Poorer sleep quality has been associated with respiratory symptoms, lower activity, more exacerbations, a lower level of education, and higher rates of anxiety and depression. However, it does not seem to be related to age, gender, smoking intensity, or FEV₁ (%). There are scales designed to measure sleep quality, such as the Pittsburgh Sleep Quality Index (PSQI), but they do not take into account the specific aspects of chronic respiratory diseases [46]. A high prevalence of sleep quality disturbances in patients with COPD has been observed using this index, similar to those observed in our study with the CASIS questionnaire; moreover, sleep quality has been significantly correlated with general and specific quality of life [47]. However, the fact that the PSQI is not a questionnaire designed for respiratory patients could be the reason why the incidence of low-quality sleep measured by the PSQI in patients with COPD, although very frequent, would not be different in a group of patients with nocturnal desaturation compared to those having normal desaturation [48]. Perhaps an index gathering more specific respiratory aspects could detect more disorders in patients with COPD, in particular if they are severe. A comparative study of the PSQI and CASIS questionnaires would be necessary to confirm this hypothesis. In any case, the CASIS questionnaire is an easy-to-use instrument which helps in the detection of sleep disorders that significantly affect the quality of life, regardless of the severity of the COPD, and that may require specific treatment.

It must be recognized that self-reported outcomes have methodological limitations [49] and, in particular, one of the limitations of the current study is its cross-sectional design, which does not allow for the establishment of causal relationships or the observation of changes following treatment intervention(s). In the future it would be important to design a study able to assess the efficacy of different interventions on these aspects of COPD, and with which frequency they are relegated to a secondary level in the health care of these patients [50].

In summary, the LCOPD, CAFS, and CASIS questionnaires have demonstrated excellent psychometric properties within a large population of patients with moderate to severe COPD. These instruments can be useful in the comprehensive assessment of patients with COPD.

This study was funded by Novartis Farmacéutica S.A., Spain. The authors thank Rupert Gale and Alastair Glendenning for their review of and contributions to this paper. Thanks also go to Steve McKenna (Galen Research), owner of the LCOPD questionnaire, and all physicians who enrolled patients into the study.