ABSTRACT
We developed a questionnaire to detect cases of chronic obstructive pulmonary disease (COPD) and compared its reliability with other strategies. In order to develop the new questionnaire (COPD screening questionnaire from Terrassa [EGARPOC]) we used data from an epidemiological study on the prevalence of COPD in smokers and calculated the odds ratio for each variable showing significance for the diagnosis of COPD on regression analysis. For comparison among questionnaires and the portable spirometer COPD-6, a cross-sectional multicenter study was performed. The study included 407 smokers or ex-smokers over the age of 40 years with no known diagnosis of COPD, who completed the different questionnaires (EGARPOC, Respiratory Health Screening Questionnaire, COPD-population screener and 2 questions) and underwent spirometry with the COPD-6. We determined the sensitivity, specificity, positive and negative predictive values (S, Sp, PPV and NPV, respectively) and the area under the receiver operating characteristic ROC curve (AUC ROC) of all the questionnaires and the different COPD-6 cut-offs. The prevalence of COPD was 26.3%. The EGARPOC questionnaire showed an S of 81.8%, an Sp of 70.6%, and an NPV of 91.8%; 73.3% of individuals were correctly classified, and the AUC ROC was 0.841. On comparing the questionnaires by the Chi-square test, the 2-question questionnaire showed the worst discrimination; while with an optimal cut-off of forced expiratory volume in one 1 second (FEV1)/FEV6 of 0.78, the COPD-6 was significantly better than the questionnaires in the detection of COPD. Using a cut-off of FEV1/FEV6 of 0.78 the COPD-6 was found to be the best screening tool for COPD in primary care compared to the questionnaires tested, which did not show differences among them.
Introduction
Early detection of chronic obstructive pulmonary disease (COPD) is important due to the known implications regarding the morbidity and mortality of these patients Citation(1–3). Diagnosis requires spirometry with a bronchodilator test, which may not always be available in Primary Care (PC) centers due to a lack of equipment or professionals trained in carrying out these tests. In these cases, the diagnosis of COPD may depend on a lengthy hospital waiting list. The high grade of underdiagnosis of COPD in Spain is well known Citation(1,2,4) and is due to not only a lack of awareness of the importance of certain respiratory symptoms by the general population, but also due to the deficient active search for this disease by health care professionals. This underdiagnosis is especially important since undiagnosed patients present significant alterations in their level of physical activity, quality of life Citation(2), and even an increase in mortality Citation(3).
Primary care is the ideal setting to correct this situation Citation(3,4). However, general practitioners should attend multiple diseases presented by their patients; thus, the performance of exhaustive tests in all of their patients is impossible. Therefore, the availability of simple, useful tools would be of great utility in order to facilitate this task.
Different questionnaires have been developed to achieve diagnosis on suspicion of the presence of COPD. Simpler, less expensive portable spirometers may allow the selection of individuals in whom conventional spirometry with a bronchodilator test (BDT) are necessary in order to achieve the definitive diagnosis of COPD. In this way we could reduce the waiting list for spirometry and facilitate the early diagnosis of COPD. However, there is no consensus as to the best strategy to use to perform an active case search in PC.
This study had three objectives: First, to develop a screening questionnaire elaborated from the analysis of a study on COPD prevalence in smokers in our setting Citation(4). Second, test the portable spirometer (Vitalograph COPD-6®) and determine the best predictive value for COPD since, to date, there is no consensus regarding the cut-off point Citation(5–7). The last objective was to compare the diagnostic yield of the new questionnaire and portable spirometry with other previously published screening questionnaires Citation(8–11).
Method
To develop a COPD screening questionnaire (EGARPOC questionnaire, derived from Egara (Terrassa) and EPOC that is COPD in Spanish), we analyzed all the data collected in a study on the prevalence of COPD carried out in 1738 smokers over the age of 40 years in PC Citation(4). Demographic and anthropometric data of the patients were collected as well as information regarding smoking habit, exposure to toxic respiratory substances in the workplace, respiratory symptoms and the presence of cardiovascular disease. Detailed information about this population has been described in the previous publication Citation(4).
For the second and third objectives we performed a cross-sectional multicenter study. This study was carried out in eight PC centers in the reference area corresponding to the Hospital Universitario de Mutua de Terrassa. Subjects over the age of 40 years who were smokers or ex-smokers of at least 1 pack-year with no previous diagnosis of COPD and who attended the PC centers for any reason during the study period were invited to participate. They were asked to fill out a questionnaire of affiliation including sex, age, anthropometric data, education, smoking habit, exposure to toxic respiratory substances in the workplace, and the presence of cardiovascular disease. Thereafter, they filled in the COPD screening questionnaires included in the study and spirometry was performed using the Vitalograph COPD-6 TM model 4000 (Buckingham, UK). The portable spirometry was performed by the PC physician, a nurse or a technician trained in the department of pneumology of the reference hospital. All the health care professionals participating in the study received a 1-hour training session in which the use of the portable spirometer was explained as well as how to identify the values to be reported: FEV1, FEV1(%), FEV6, FEV6(%), FEV1/FEV6, estimated pulmonary age and the color shown on the screen indicating the probability of having COPD (green: improbable COPD, yellow: possible COPD or red: probable COPD).
Lastly, all the patients underwent conventional spirometry with the Blue Spiro of Ergometrics® (Esplugues de Llobregat, Barcelona, Spain). This test was always performed by a technician trained in spirometry following the international recommendations Citation(12). If the FEV1/Forced vital capacity (FVC) quotient was <0.7, another spirometry was carried out 15–20 minutes after the inhalation of 400 µg of salbutamol. The patient was considered to have COPD when the post-bronchodilator FEV1/FVC was <0.7. The results were compared with those obtained using the lower limit of normal (LLN) of post-bronchodilator FEV1/FVC to establish the diagnosis of COPD. The reference values from Roca et al. Citation(13) were used.
In addition to the EGARPOC questionnaire given in the first part of the study, the following questionnaires were used in their Spanish validated versions: (a) the Respiratory Health Screening Questionnaire (RHSQ) Citation(8), which has 10 questions related to age, smoking habit, body mass index (BMI) and respiratory symptoms. The sum of the score of each item ranges from 0 to 38, with a value greater than 17 indicating the very probable presence of COPD; (b) the COPD-population screener (PS) Citation(9,10) which has 5 questions scored from 0 to 2 with the minimum score being 0 and the maximum 10. Scores greater than or equal to 4 show optimal predictive properties to suspect COPD; (c) two screening questions (2SQ) regarding smoking and chronic bronchitis proposed by Kögler et al. Citation(11). Affirmative answers to these two questions have been used in screening for COPD.
The study was approved by the administrative boards of the different centers and the Research and Ethics Committee of the Hospital Universitario Mutua de Terrassa. All the participants provided signed informed consent.
Statistical analysis
For the development of the EGARPOC questionnaire, all the variables significantly associated with the diagnosis of COPD on univariate analysis were included in a multivariate logistic regression analysis with the dependent variable COPD (yes/no). The degree of association was analyzed by odds ratios (ORs) (95% confidence intervals [CIs]) and goodness of fit was analyzed by pseudo R2 statistics. The variables obtained and their weights were used to design the questionnaire. The sensitivity (S), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), the percentage of patients correctly classified and the receiver operating characteristic (ROC) curves were established for validation and determination of the best cut-off for this tool.
Sample size calculation for the study of comparison of the different questionnaires and the COPD-6 was estimated based on the S and Sp of the portable spirometer of 86% and 91%, respectively Citation(6,14) and for a prevalence of COPD in smokers of 24.3% obtained in our previous study Citation(4). Considering a statistical power of 80%, the required sample size was 331 participants including 25% of non-responders or individuals ruled out due to difficulties in spirometry maneuvers. The final estimation of the sample size was 413 subjects.
Qualitative variables are expressed as percentages and confidence intervals (CI) while quantitative variables are expressed as medians and standard deviation (SD).
Differences between sex and patients with and without COPD were analyzed by bivariate analysis with the χ2 and the Fisher exact test for qualitative variables and with the Student's t-test or ANOVA for the quantitative variables or the corresponding nonparametric tests (Mann-Whitney U, Kruskal-Wallis). Prior to this, the normal distribution and homogeneity of the variances was determined using the Kolmogorov-Smirnov and Leven tests, respectively.
The S, Sp, PPV, NPV, the percentage of patients correctly classified and the ROC curves were determined for the different questionnaires as well as the different cut-offs of FEV1/FEV6 of the COPD-6. We also compared the areas under the ROC curves (AUCs) among the different tools using Chi-square analysis.
A p-value <0.05 or a CI which did not include the unit was considered statistically significant. The statistical analyses were performed using the SPSS v.16 and STATA/SE v.9.0 programs.
Results
Development of a COPD screening questionnaire (EGARPOC questionnaire)
shows the OR values with the CI 95% for each variable, which was significant in the multivariate analysis. Using these values, the EGARPOC questionnaire was elaborated with 9 items (annex 1). The score of the questionnaire ranges from 0 to 29. Using ROC curve analysis, an optimal value of 13 was obtained with an S of 81.8%, an Sp of 70.6%, a PPV of 49%, an NPV of 91.8%, and with a percentage of correctly classified individuals of 73.3% (). The AUC for evaluating the goodness of fit of the questionnaire was 0.841 (95% CI: 0.820–0.863).
Table 1. Independent variables for COPD obtained in the prevalence study (n = 1738 individuals) used for developing the EGARPOC questionnaire.
Figure 1. Area under the ROC curve for the EGARPOC questionnaire. Footnote: AUC ROC: 0.841 (0.820–0.863).
Study of questionnaire comparison: Description of the population and prevalence of COPD
A total of 417 individuals participated in the study comparing the questionnaires, with 10 being excluded due to incorrect spirometry. Of the 407 subjects included, COPD was confirmed by fixed ratio in 107 cases (26.3%), 14.8% among women and 32.5% among men. Of the cases with COPD 42.1% were mild, 49.1% moderate and 8.4% severe, with no patient in very severe Global strategy for Obstructive Lung Disease (GOLD) stage. Au: Please provide the expansion for ‘GOLD’. Using the LLN there were 86 (20.6%) individuals with criteria of COPD, 6 of them only fulfilled the LLN criterion but not the fixed ratio and were aged 44–56 years. The 27 patients with COPD by fixed ratio but not by LLN were all older than 60 years of age.
shows the characteristics of the participants by sex; 65.2% were men, with a mean age of 57.4 years, 56.5% were active smokers, a higher percentage of which were women. The presence of cardiovascular disease was 8.6%. Distribution of severity was very similar when considering patients identified by LLN ().
Table 2. Characteristics of the individuals included in the validation study of the questionnaires and COPD-6.
Among the patients with COPD the mean age and the number of pack-years were significantly higher, and the educational level lower than the remaining individuals. The values of conventional spirometry were significantly lower in subjects with COPD except for the FVC, which did not achieve statistical significance ().
Table 3. Results of the comparison between individuals with and without COPD in the validation study population.
Validation of the COPD-6: Identification of the cut-off
Portable spirometry was carried out by a primary care nurse in 34.4% of the cases, by a family physician in 37.3% and by a spirometry technician in 28.3%. No significant differences were observed in the percentage of COPD diagnoses in each group (30%, 21.7% and 27.8%, respectively; p = 0.249).
Significant differences were found between individuals with or without COPD in all the parameters obtained with the COPD-6 in both populations of COPD patients diagnosed either by fixed ratio or by LLN (). To assess the diagnostic goodness of fit of the portable spirometry the area under the ROC curve was calculated to be 0.873 (95% CI: 0.835–0.909) (). The best cut-off of the FEV1/FEV6 ratio was 0.78 (; this cut-off allowed correct diagnosis of 87.9% of patients with COPD with only 27.7% of false positive results ().
Table 4. Results of the comparison of portable spirometry values and those of the questionnaires in individuals with and without COPD by fixed ratio and LLN.
Figure 2. Diagram of the area under the ROC curve of the questionnaires and the FEV1/FEV6 of the portable spirometer; p < 0.0001.
Table 5. Evaluation of the properties of each cut-off of FEV1/FEV6 of the COPD-6 and those of the different questionnaires tested.
Figure 3. Percentage of patients who are not diagnosed with COPD (undiagnosed patients) and the percentage of unnecessary spirometry performed (healthy) for the different cut-offs of the portable spirometer.
Comparison of the diagnostic accuracy of the different questionnaires and COPD-6
All the questionnaires used and the COPD-6 showed significantly different results between the individuals with and without COPD (). The degree of statistical significance was lower with the 2SQ questionnaire.
On comparing the different tools, the COPD-6 showed a significantly greater AUC ROC than the different questionnaires used, and the 2SQ showed significantly lower diagnostic accuracy. On the other hand, no significant differences were observed among the three remaining COPD screening questionnaires (EGARPOC, RHSQ and COPD-PS) ( and ).
Discussion
The present study shows that the portable spirometer COPD-6 provides greater diagnostic accuracy than screening questionnaires for the detection of COPD in PC. In addition, it has shown that a cut-off of 78% of the FEV1/FEV6 quotient provided the best discriminatory power in subjects with or without COPD in our population. On the other hand, the diagnostic validity of the EGARPOC questionnaire designed from data obtained in our area was similar to that of other previous questionnaires but showed a greater percentage of correctly classified patients.
The PC setting is the most adequate to reduce the underdiagnosis of COPD Citation(15–17). It is well known that despite the multiple opportunities provided by the longitudinal and integrated care provided by PC for the early diagnosis of COPD, many centers miss patients and they remain undiagnosed despite multiple contacts with the health care system Citation(18). The situation of general physicians is particularly complex due to the multiple diseases which must be known, treated and followed, and the limitations in time and resources available make the need for simple useful tools essential to facilitate their work with the most prevalent diseases such as COPD. Several studies in Spain have found that in more than 50% of the cases the clinical history of the patients described a diagnosis of COPD without the patients having undergone spirometry, and among many of those with spirometry results an obstructive pattern was not observed Citation(19,20). In addition, access to spirometry may be even more limited in rural centers Citation(21).
Despite the many studies published to date, there is no definitive recommendation as to the most adequate tool or procedure for the screening of COPD in populations at risk. Although conventional spirometry is the gold standard for the diagnosis of COPD, its application in screening for COPD in the general population is not considered cost-effective Citation(22). Therefore, in the present study we compared different screening methods in individuals at risk: office spirometry with the COPD-6, previously published questionnaires, and a questionnaire designed from the analysis of data from a previous study on the prevalence of COPD in our population setting Citation(4).
Most screening questionnaires for COPD have reported good accuracy with AUC ROC curves of 0.75–0.85 Citation(8,23). However, when these questionnaires are used in other populations this accuracy is usually lower. For example, the RHSQ obtained an AUC ROC curve of 0.82 in the initial validation study Citation(8), but only 0.67 in a study in Germany and Belgium Citation(24) and 0.72 in Australia Citation(25). It is also possible that different populations may require different cut-off values to maintain the diagnostic value obtained in the original setting Citation(26). Taking into account the different behaviors of the screening questionnaires in different populations we decided to develop a questionnaire from the analysis of data from a study on prevalence performed in our setting Citation(4). In general, the variables most frequently identified for incorporation in screening tools are: age, pack-years and the presence of respiratory symptoms (expectoration, cough, wheezing and dyspnea) Citation(27), all of which were also included in our questionnaire. In our EGARPOC questionnaire the presence of COPD increases with age, smoking, the presence of expectoration and dyspnea, with a lower BMI and with a history of having worked in a profession considered to be of risk for pulmonary disease. These variables have been used in previously developed questionnaires Citation(8,24–28). The probability of COPD also increases with affirmative response to the questions “colds always go to my chest” and “treatment was needed to stop an attack of breathlessness.” In our questionnaire we included the coexistence of cardiovascular disease (ischemic heart disease, cerebrovascular disease or intermittent claudication) as a differential characteristic.
In the population studied to compare the questionnaires and the COPD-6 we found a prevalence of COPD of 26.3%, which was practically identical to the 24.3% obtained in the previous prevalence study performed in a population with the same characteristics Citation(4). Of note, the percentage of smoker women was greater than that of men (62.2% versus 53.6%, respectively), leading to the prediction of an increase in the prevalence of COPD among women in the next years. In this population we first investigated the best cut-off for the identification of COPD cases with the COPD-6 office spirometer. This device measures the FEV1 and FEV6 as an acceptable alternative to FVC and does not require special training to carry out. Correct obtainment of FVC is the most critical point in the use of conventional spirometry for the detection of COPD in PC Citation(29), and the use of a pocket spirometer able to measure FEV6 as a screening tool may reduce the need for conventional spirometries, which are more expensive and complex to perform Citation(5,30–32). Although 2.4% of our patients did not undergo a standard spirometry, all underwent an adequate COPD-6 spirometry. The best cut-off obtained in our study was 0.78, which allowed correct classification of 87.9% of the individuals participating in the study. This cut-off is higher than the 0.75 identified in another Spanish study that correctly classified 85% of subjects Citation(10). Studies performed in other countries have provided different cut-offs most of which were between 0.70 and 0.76 Citation(5,6,33–35).
The diagnostic value of the COPD-6 was significantly better than that of the questionnaires used. These results are particularly relevant because all the tools were tested in the same population. A previous meta-analysis of COPD screening tools in PC including 10 studies, 8 of which used questionnaires and two portable spirometers, also found that portable spirometer was more accurate. However, these results have important limitations due to methodological differences, diagnostic criteria and the different populations of the studies included in the analysis and a great variability among the different studies existed, making interpretation of the results difficult Citation(36).
With regard to the questionnaires, all showed a lower diagnostic capacity than that published in the original validation studies. Nonetheless, it can be concluded that questionnaires are very useful tools although they may lose diagnostic capacity on application to other populations. The diagnostic capacity of the EGARPOC questionnaire was similar to that of the remaining questionnaires, but with a higher number of correct classifications of the participants. It was of note that the results of the questionnaire proposed by Kögler et al. Citation(11), which included only two questions, were significantly worse than those of the remaining tools tested.
Our study has some limitations including the heterogeneity of the participating investigators and their possible lack of experience. To avoid this all the investigators were given a training session to provide an in-depth explanation of the technique and to standardize the methodology, and in the end no differences were observed in the results obtained by nurses, physicians or spirometry technicians. The determination of the time used for the explanation to the patients and the performance of the COPD-6 as well as the collection of the information in the questionnaires would have provided objective, useful data for finding the best screening tool but would have required an external observer, adding greater complexity to the study design. We used the fixed ratio as the gold standard for the diagnosis of COPD, but we also calculated the prevalence by the LLN and the results were very similar. Discrepancies were observed in relation to the age of the participants confirming the observation that the fixed ratio may lead to some underdiagnosis in the younger age groups and overdiagnosis in the elderly Citation(37).
In conclusion, the pocket spirometer COPD-6 is the best COPD screening tool in PC with a cut-off of 0.78 in our setting. The validity of the new EGARPOC questionnaire is similar to that of the other COPD screening questionnaires currently available. In cases in which the pocket spirometry is not available, questionnaires may be a good alternative to detect individuals requiring diagnostic spirometry.
Declaration of interest
Marc Miravitlles has received speaker fees from Almirall, Boehringer Ingelheim, AstraZeneca, Chiesi, GlaxoSmithKline, Menarini, Teva, Grifols and Novartis, and consulting fees from Almirall, Boehringer Ingelheim, GlaxoSmithKline, Gebro Pharma, CLS Behring, Cipla, MediImmune, Teva, Takeda, Novartis and Grifols. The remaining authors have no conflicts of interest to declare in relation with this manuscript.
Members of the primary care respiratory group HUMT:
Ángela Garreta, Antonia Correas, Trini Izquierdo, Laura Pineda, Carme Viñas, Fauri Tamayo, Inma Serra, Javier López, Cristina Moncholi, Maite Mellado, Conchi Bistuer, Esteban López, Montse Gavagnach, Lourdes Magem, Teresa Mur, Sergi Abad, Gemma Miranda, Marta Miranda, Ana Rosales, Mª José Perona, Luis Heredia, Pilar Solé and Mercè Mora.
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Marc Miravitlles http://orcid.org/0000-0002-9850-9520
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