Patient characteristics

In total 814 patients were considered in the development cohort (secondary care cohort). Patients were excluded for this study because of missing data (n = 307) or when CCQ and ACQ were not completed on the same day (n = 106). So, in total 252 asthma patients and 97 COPD patients were included in the development cohort, Fig. 1. In the asthma group 162 (64.3%) were female and in the COPD group 42 (43.8%), Table 1. The median age [IQR] of the asthma patients was 48.5 years old [38.3–59.0] and in COPD 63.0 years old [55.0–70.0]. There were more active smokers in the COPD group, compared to the asthma group (52.1% vs. 12.7%, <0.001). The median FEV-1 post bronchodilator percentage predicted [IQR] was higher in asthma patients compared to the COPD patients (93% [79–104] vs. 66% [52–82]). The items of the ACQ and CCQ differed significantly between asthma and COPD in the questions ACQ 1, ACQ 2, CCQ 1, and CCQ 6, Suppl. Fig. 1. Median scores of ACQ 2 and CCQ 1 were higher in asthma patients, compared to COPD patients and ACQ 1 and CCQ 6 scores were elevated in COPD patients.

Fig. 1

Patient enrolment of secondary care cohort and primary care cohort.

Table 1 Patient characteristics in secondary and primary cohort.

The first reproduction cohort included 53 ACO patients from the secondary care data, Fig. 1. In this patient group 22 (41.5%) were female and 19 (35.8%) were active smokers. The median age was 61 [55–68], Suppl. Table 1. In total 1110 asthma patients and 1041 COPD patients of the primary care cohort were included in the second cohort, Fig. 1. In this primary care cohort, the patients in the COPD patient group were older (64 y [57–71] vs. 43 y [28–56]), and more men (52.4% vs. 44.3%) and active smokers were included compared to the asthma patient group (49% vs. 20%), Table 1. The third and final reproduction cohort included 355 ACO patients of the primary care dataset. In this group 165 (46.5%) were female and 148 (41.7%) were active smokers. The median age was 59 [50–68], mean FEV-1 post bronchodilator percentage predicted was 74.4 [61.4–84.6] and median FER was 60.7 [53.5–65.6], Suppl. Table 1.

Correlation between the ACQ and CCQ

In the secondary care cohort, the Pearson correlation coefficient (R) between the ACQ and CCQ was 0.82 in asthma patients, 0.83 in COPD patients, and 0.83 in ACO patients. In the primary care cohort, R was 0.81 in asthma patients, 0.80 in COPD patients and 0.81 in ACO patients, Fig. 2.

Fig. 2: Correlation plot showing the correlation between the ACQ and CCQ in secondary cohort (left) and in primary cohort (right).

In the secondary cohort, the Pearson correlation coefficient (R-score) was 0.82 in asthma patients, 0.83 in COPD patients, and 0.83 in ACO patients. In the primary cohort, the R-score was 0.81 in asthma patients, 0.80 in COPD patients and 0.81 in ACO patients.

Selecting questions of the ACQ and CCQ in the development cohort

Principal Component Analysis (PCA) was performed to integrate the ACQ and CCQ and reduce the number of questions. Three components were formed based on correlations between questions. Component 1 consists of: CCQ 7, CCQ 8, CCQ 2, CCQ 9, and ACQ 3. Component 2 consists of CCQ 6 and CCQ 5 and component 3 consists of CCQ 3, CCQ 4, ACQ 2. The CCQ 10, ACQ 4, ACQ 5, CCQ 1 and ACQ 1 were not correlated with the other items and therefore not included in a component, Fig. 3. This process of data reduction resulted in the selection of eight required questions: one question was selected for each component (CCQ 7 in component 1, CCQ 6 in component 2, CCQ 3 in component 3); and the residual questions (CCQ 10, ACQ 4, ACQ 5, CCQ 1, and ACQ 1).

Fig. 3: Results of Principal component analyses in secondary cohort and primary cohort, in asthma, COPD, and asthma-COPD overlap patients.

The red box contains the questions of that particular component. PC1 = component 1; PC2 = component 2; PC3 = component 3. ACQ 1: on average, during the past week, how often were you woken by your obstructive lung disease during the night?; ACQ 2: on average, during the past week, how bad were your obstructive lung disease symptoms when you woke up in the morning?; ACQ 3: In general, during the past week, how limited were you in your activities because of your asthma?; ACQ 4: in general, during the past week, how much shortness of breath did you experience because of your obstructive lung disease?; ACQ 5: in general, during the past week, how much of the time did you wheeze?; CCQ 1: on average, during the past week, how often did you feel short of breath at rest?; CCQ 2: On average, during the past week, how often did you feel short of breath doing physical activities?; CCQ 3: On average, during the past week, how often did you feel concerned about getting a cold or your breathing getting worse?; CCQ 4: On average, during the past week, how often did you feel depressed (down) because of your breathing problems?; CCQ 5: In general, during the past week, how much of the time did you cough?; CCQ 6: in general, during the past week, how much of the time did you produce phlegm?; CCQ 7: on average, during the past week, how limited were you in these activities because of your breathing problems: strenuous physical activities (such as climbing stairs, hurrying, doing sports)?; CCQ 8: On average, during the past week, how limited were you in these activities because of your breathing problems: moderate physical activities?; CCQ 9: On average, during the past week, how limited were you in these activities because of your breathing problems: daily activities at home (such as dressing, washing)?; CCQ 10: on average, during the past week, how limited were you in these activities because of your breathing problems: social activities (such as talking, being with children, visiting friends/relatives).

Reproduction of selection procedure in three cohorts

The selection procedure of the questions was repeated in three reproduction cohorts: (1) patients with ACO in the secondary cohort; (2) patients with asthma and COPD of in the primary care cohort; (3) the patients with ACO in the primary care cohort. As in the development cohort, the answers of ACQ and CCQ questions were combined into one dataset and questions were reduced by PCA.

The PCA of the data of the ACO patients in the secondary dataset showed similar results as the development cohort with a few exceptions. Component 1 also consists of CCQ 7, CCQ 8, CCQ 2, and ACQ 3; however, it contains the ACQ 4 instead of the CCQ 9. Component 2 in this reproduction cohort is identical to component 2 in the development cohort. Component 3 also consists of the CCQ 3, but contains the ACQ 1 instead of the CCQ 4 and ACQ 2, Fig. 3.

In the primary care data of the patients with asthma or COPD, the PCA resulted in similar components as in the development cohort; except for ACQ 2 which had a lower correlation value for component 2 in primary care in comparison with secondary care (0.505 vs. 0.709). Component 1 consists of resp.: CCQ 7, CCQ 8, CCQ 2, CCQ 9 and ACQ 3. Component 2 consists of CCQ 6 and CCQ 5 and component 3 consists of CCQ 3, CCQ 4. The residual questions were ACQ 1, ACQ 2. ACQ 4, ACQ 5, CCQ 1 and CCQ 10, Fig. 3.

The PCA with data of the asthma-COPD overlap patient group in the primary care data yielded similar results. Component 1 consists of resp.: CCQ 8, CCQ 7, CCQ 2, CCQ 9 and ACQ 3. Component 2 consists of CCQ 6 and CCQ 5 and Component 3 consists of CCQ 3, CCQ 4. The residual questions were ACQ 1, ACQ-2. ACQ 4, ACQ 5, CCQ 1 and CCQ 10, Fig. 3.

Development of the Obstructive Lung Disease Questionnaire

Combining the results of the four PCA’s resulted in a selection of 9 questions. For each component, the question with the highest correlation in the development cohort was included in our selection. Component 1, containing the CCQ 7, CCQ 8, CCQ 2, CCQ 9 and ACQ 3, the CCQ-7 was selected as the identifying question of this component. These five questions were about complaints during physical activity; more specifically: shortness of breath during physical exercise (CCQ 2), limitations because of intense physical activity (CCQ 7), or moderate physical activity (CCQ 8), or daily activities (CCQ 9), or limitations because of activity (ACQ 3).

The CCQ 6 was selected from component 2. Both questions in component 2 are about coughing: CCQ 5 is about the amount of coughing and CCQ 6 is about the amount of sputum during coughing. CCQ 3 was selected as the identifying question of component 3, which contained the CCQ 3 and CCQ 4. CCQ 3 is a question about feeling concerned and the CCQ 4 about feeling depressed because of respiratory complaints. ACQ 2 was also statistically correlated with CCQ 3 and CCQ 4 in the development cohort. However, the ACQ 2 was not included in component 3 in any of the reproduction cohorts. Therefore, the ACQ 2 was not merged with the CCQ 3 and CCQ 4. The ACQ 1, ACQ 4, ACQ 5, CCQ 1 and CCQ 10 were not statistically correlated to any of the components. These questions were included in the final selection. This process resulted in a 9-item questionnaire with a 6 point scale with working title ‘’the Obstructive Lung Disease Questionnaire (OLD-Q)”. ‘’Asthma” was replaced for ‘’obstructive lung disease” to make the questionnaire applicable for all patients, Table 2.

Table 2 Working title ‘’Obstructive Lung Disease Questionnaire” as a potential new tool for measuring disease burden in obstructive lung disease.Validity and reliability of the Obstructive Lung Disease Questionnaire

In asthma patients, the correlation coefficient of the ACQ and total score of OLD-Q was 0.93 in the secondary cohort and 0.94 in the primary cohort. The correlation coefficient between the CCQ and the OLD-Q in COPD patients was 0.94 in the secondary cohort and 0.93 in the primary cohort, Fig. 4. The correlation coefficient in COPD (n = 61) between CAT and OLD-Q was 0.723 and between CCQ and CAT was 0.731. The correlation coefficient in asthma (n = 197) between AQLQ and OLD-Q was -0.686 and for AQLQ and ACQ total -0.652. The Cronbach’s alpha of the OLD-Q in the secondary care was for asthma: 0.877, for COPD patients: 0.885, and for ACO patients: 0.884. In primary care, the Crohnbach’s alpha was for asthma patients 0.867, for COPD 0.858 and for ACO 0.858.

Fig. 4: Correlation plots.

Correlation plot showing the correlation between the ACQ and the OLD-Q in asthma patients in secondary cohort (A) and primary cohort (B) and the correlation between the CCQ and the OLD-Q in COPD patients in secondary cohort (C) and primary cohort (D). The Pearson correlation coefficient (R-score) was respectively 0.93 (A), 0.94 (B), 0.94 (C), and 0.93 (D).