Copyright ©ERS Journals Ltd 2008 External validation of a COPD diagnostic questionnaire1 Depts of General Practice, 3 Epidemiology, 2 School for Public Health and Primary Care (CAPHRI), Maastricht University, and 4 Dept of Respiratory Medicine, Maastricht University Hospital, Maastricht, The Netherlands. CORRESPONDENCE: D. Kotz, Dept of General Practice, School for Public Health and Primary Care (CAPHRI), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Fax: 31 433619344. E-mail: d.kotz{at}hag.unimaas.nl Keywords: Chronic obstructive pulmonary disease, diagnostic questionnaire, early diagnosis, external validation, spirometry
Received: June 20, 2007
The aim of the present study was to determine the external validity of a recently developed questionnaire for the identification of patients at increased risk of airflow limitation in smokers from the general population in the provinces of Dutch and Belgian Limburg (regions surrounding Maastricht, the Netherlands).
As part of a study on the early detection of airflow limitation and subsequent smoking cessation treatment (International Standard Randomised Controlled Trial Number: 64481813), the recently developed chronic obstructive pulmonary disease (COPD) diagnostic questionnaire was used in current smokers aged 40–70 yrs, with a smoking history of Of the 676 subjects who entered the analyses, 398 showed normal lung function and 278 had a diagnosis of COPD (post-bronchodilator forced expiratory volume in one second/forced vital capacity of <0.70). The ability of the COPD diagnostic questionnaire to discriminate between subjects with and without COPD was poor (area under the receiver operating characteristic curve of 0.65).
In a high-risk population consisting of middle-aged current smokers with a smoking history of Chronic obstructive pulmonary disease (COPD) is associated with a high personal and societal burden and mortality. Projections for 2020 indicate further increase in global COPD mortality, making COPD the third leading cause of death 1. Underdiagnosis of COPD is a worldwide problem 2. Most patients present to their doctor for various other reasons but often have respiratory symptoms, and, in those who present with respiratory symptoms, COPD is not always diagnosed 3. Owing to the irreversible and progressive nature of the disease, early identification of COPD and subsequent treatment is important. However, widespread spirometric testing for early detection without pre-selection of at-risk patients may result in wasting healthcare resource utilisation 4, 5.
The efficiency of early detection of COPD can be enhanced (in terms of detection rate and accuracy) by using simple self-administered questionnaires to identify persons in whom airflow limitation is likely 6, 7. Price and co-workers 8, 9 have developed a new symptom-based questionnaire for the identification of patients at increased risk of airflow limitation. Their COPD diagnostic questionnaire discriminates between subjects with and without airflow limitation. These authors concluded that their questionnaire could be used to identify patients with a high likelihood of showing airflow limitation, and that combining it with spirometry could help to improve the efficiency and accuracy of COPD diagnosis in primary care 8, 9. The questionnaire has recently been implemented in the guideline for chronic airways diseases of the International Primary Care Airways Group 10. The guideline recommends use of the questionnaire in current and former smokers aged Before a new diagnostic questionnaire can be accepted and applied reliably in clinical practice, the analysis of the underlying model must be repeated on new data collected from an appropriate sample of subjects in a different setting 11–13. This process is called external validation. The aim of the present study was to determine the validity of the COPD diagnostic questionnaire in current smokers from the general population in the provinces of Dutch and Belgian Limburg.
Development of the COPD diagnostic questionnaire in the original sample The development of the COPD diagnostic questionnaire has been described in detail elsewhere 8, 9. In brief, 818 participants completed a list of questions and underwent spirometry. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline 14 by a post-bronchodilator (post-BD) forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of <0.70. Multiple logistic regression models were constructed in order to identify eight items for discriminating between persons with and without COPD. The scoring system of the questionnaire permits calculation of an overall COPD risk based on the weighted scores for these items. The sum score ranges 0–38 points. According to the manual of the questionnaire, subjects can be classified as being at high (>19.5 points), moderate (16.5–19.5 points) or low (0–16.5 points) risk of COPD. The area under the receiver operating characteristic (ROC) curve (ROCAUC) was 0.82. The diagnostic odds ratios (DORs) of the two cut-off points, 16.5 and 19.5, were 5.5 and 4.8; calculation based on that of Price et al. 9.
External validation sample Subjects were recruited from the general population (through advertisements in a local newspaper, flyers, posters and mailings to households) and from primary care practices (during consultations and through posters and personalised mailings) in the provinces of Dutch and Belgian Limburg (the region surrounding Maastricht, the Netherlands) during the period January 2005 to December 2006. Smokers aged 35–70 yrs who were current smokers but motivated to quit smoking were invited to take part in a study on individual counselling and medication for smoking cessation. The external validation of the COPD diagnostic questionnaire was performed in current smokers aged 40–70 yrs.
Eligibility was screened during an initial telephone interview. Inclusion criteria were: a smoking history of After the initial telephone interview, participant information, along with the informed consent form and the COPD diagnostic questionnaire, was sent to eligible subjects and a date was fixed for spirometry. Linguistic validation of the original English COPD diagnostic questionnaire for use in Dutch-speaking people had been performed by an experienced international research institute (Mapi Research Institute, Lyon, France). This process comprised conceptual definition of items, forward and backward translation, and testing. Subjects filled in the questionnaire at home and handed it in during the spirometry visit, during which they also signed the informed consent form. Spirometry was performed by two qualified research assistants under the permanent supervision of a pulmonologist (G.J. Wesseling) according to the criteria of the American Thoracic Society/European Respiratory Society task force on standardisation of lung function testing 15, 16 using a Vitalograph® 2120 (Vitalograph, Buckingham, UK). After a minimum of three acceptable and reproducible FVC manoeuvres, a bronchodilator (500 µg terbutaline) was administered to the subject in preparation for the reversibility test. After 15 min, another series of three FVC manoeuvres was performed. All spirometric test results were independently validated by a pulmonologist (G.J. Wesseling) and a specialised lung function laboratory assistant who was not involved in the trial. Both were blinded to the scores on the COPD questionnaire. In the case of initial disagreement, consensus was obtained during re-examination. As in the study of Price and co-workers 8, 9, a diagnosis of COPD was confirmed by a post-BD FEV1/FVC of <0.70, according to the international GOLD guideline 14.
Statistical analyses
Study population A summary of the study enrolment protocol is shown in figure 1
Characteristics of the external validation sample Of the 676 study subjects, 378 (59%) exhibited normal lung function (mean post-BD FEV1/FVC of 77.9; mean post-BD FEV1 of 94.1% of the predicted value) and 278 (41%) had a diagnosis of COPD (mean post-BD FEV1/FVC of 61.9; mean post-BD FEV1 of 79.7% pred). In the latter group, airflow limitation according to GOLD criteria 14 was mild in 142 (21%) subjects, moderate in 119 (18%) and severe-to-very severe in 17 (3%). All other characteristics are shown in table 1
Discriminative ability of the COPD diagnostic questionnaire When applying the two cut-off points from the questionnaire manual (16.5 points for a low risk and 19.5 points for a high risk), 127 (19%) out of 676 subjects were categorised as having a low risk of COPD, 183 (27%) as having a moderate risk and 366 (54%) as having a high risk. Within these three risk categories, the observed prevalence of COPD was 24% (30 out of 127 subjects) in the low-risk category, 36% (65 out of 183) in the moderate-risk category and 50% (183 out of 366) in the high-risk category. The ability of the COPD diagnostic questionnaire to discriminate between subjects with and without COPD is shown graphically by the ROC curve in figure 2
Refit of the multiple logistic regression model The results of the multiple logistic regression analysis that modelled the probability of having COPD versus not having COPD are shown in table 2
Since age seemed to be the most important predictor of the disease, another ROC curve was calculated, with age as the single factor for predicting COPD. This curve is shown in figure 2
In the present study, the validity of a recently developed COPD diagnostic questionnaire was tested in 676 current smokers from the general population in Dutch and Belgian Limburg. The discriminative ability of the questionnaire was poor (ROCAUC of 0.65).
The COPD diagnostic questionnaire was developed in order to improve the efficiency and accuracy of COPD diagnosis in primary care by discriminating between subjects with and without airflow limitation 8, 9. When applying the cut-off points from the manual, the questionnaire reached sensitivities of 65.8 and 89.2% (at cut-off points of 19.5 and 16.5, respectively). However, the corresponding specificities were only 54.0 and 24.4%, respectively. This means that, at the cut-off point of 16.5, almost nine out of 10 subjects with airflow limitation were correctly identified by the questionnaire (true positive). However, at the same time, almost three-quarters of subjects without airflow limitation were incorrectly classified by the questionnaire as having COPD (false positive). A diagnostic test that is intended to discriminate between subjects with and without a disease should combine high levels of sensitivity and specificity. The ROCAUC, however, was very low at 0.65 (a ROCAUC of 0.50 indicates a totally uninformative test 11). The combination of the eight items of the COPD diagnostic questionnaire did not perform better than the item age alone (ROCAUC of 0.67). Another indicator for the discriminative ability of the questionnaire, the DOR, was also very low at 2.67 at the cut-off point of 16.5. The DOR ranges 0–
Why does the COPD diagnostic questionnaire show such a low external validity? It is not unusual that newly developed diagnostic questionnaires perform more poorly when evaluated in an external sample of subjects in a different setting. An important reason for the poor performance of the COPD diagnostic questionnaire is that the present sample differs from the original one. This external validation formed part of a study on the early detection of smokers with airflow limitation and subsequent smoking cessation treatment. Subjects from the present sample were all current smokers with a smoking history of An explanation for the difference in performance may be the difference in smoking status between the present external validation sample and the original sample. The present authors suggest that the COPD diagnostic questionnaire discriminates between current smokers and former or nonsmokers, rather than between subjects with and without airflow limitation. Previous research has shown that smoking exerts acute effects on respiratory symptoms. For example, in the Nord-Trøndelag Health Study, which is a population-based study of >65,000 subjects, a significantly higher proportion of smokers compared to ex-smokers reported symptoms of wheezing, breathlessness, daily coughing and coughing with phlegm 20. Respiratory symptoms were also very common among smokers from the present study; 91% of the subjects initially screened reported one of the three symptoms cough, sputum production and shortness of breath, and only 9% had none of these three symptoms. It is unlikely that exclusion of this small proportion of subjects from the present study led to a selective study sample. Since smoking correlates so closely with the presence of respiratory symptoms, the present authors believe that the development and use of diagnostic questionnaires for COPD should be undertaken separately in current and former smokers. Ultimately, such a questionnaire is not intended to discriminate between the presence and absence of respiratory symptoms, but rather between having COPD and not having COPD. It would be interesting to re-analyse the performance of the questionnaire in the two subgroups of smokers and former smokers from the original dataset. Apart from their smoking status, subjects from the present external validation sample were younger and showed slightly worse lung function parameters than those from the original sample. Furthermore, the proportion of invalid test results was higher (17 versus 9%). This may be due to a greater measurement error, or to more conservative criteria for the assessment of quality. Nevertheless, it is unlikely that the exclusion of subjects with invalid test results affected the present results since subjects with invalid test results showed similar characteristics to those with valid test results. The prevalence of COPD was much higher in the present sample (41%) than in the original one (19%). However, it is unlikely that this higher prevalence affected the discriminative ability of the questionnaire since ROC curves and the DOR are not dependent upon the prevalence of disease (although they are influenced by the spectrum of disease severity) 17, 21.
Based on the results of the present external validation study, it is concluded that the chronic obstructive pulmonary disease diagnostic questionnaire is probably not useful as a diagnostic tool for the identification of patients at increased risk of airflow limitation. The questionnaire does not discriminate between subjects with and without airflow limitation in a high-risk population (i.e. middle-aged current smokers with a smoking history of
This study was supported by grants from the Dutch Asthma Foundation (Leusden, the Netherlands), Partners in Care Solutions for COPD (the Netherlands), and Maastricht University Hospital (Maastricht, the Netherlands).
A statement of interest for C.P. van Schayck can be found at www.erj.ersjournals.com/misc/statements.shtml
The authors gratefully acknowledge the contributions of K. van der Meer (telephonic screening and logistics; Maastricht University, Maastricht, the Netherlands), A. van de Voorde (Maastricht University Hospital, Maastricht, the Netherlands) and E. de Goeij (spirometry; Maastricht University, Maastricht, the Netherlands), M. Aussems (validation of spirometric test results), W. de Goeij (database construction; Infoficiency, Ulestraten, the Netherlands) and P. Rinkens (data cleaning; Maastricht University, Maastricht, the Netherlands).
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