Abstract
BACKGROUND: FEV6 can be used as a convenient alternative to FVC. The aim of this study was to determine an alternative to the fixed cutoff points of FEV1/FVC <0.70 suitable for FEV1/FEV6 in primary care.
METHODS: Pulmonary function testing was conducted on volunteers recruited from 4 community centers in Xi'an, China, between July and August 2012. Participants underwent 3 FVC maneuvers. The maneuver with the best FEV1 was retained. FVC, FEV1, and FEV6 were measured by portable spirometer. The receiver operating characteristic curves that corresponded to the optimal combination of sensitivity and specificity for FEV1/FEV6 were determined. A kappa test was used to compare the agreement between FEV1/FVC and FEV1/FEV6. The positive predictive value and negative predictive value were also calculated.
RESULTS: A total of 767 volunteers participated in this study, of whom 297 were male and 470 were female. Considering FEV1/FVC <0.70 as the accepted standard for COPD, the area under the curve was 98% (P < .001), and the FEV1/FEV6 cutoff, corresponding to the greatest sum of sensitivity and specificity, was 0.72. For the total population, the FEV1/FEV6 sensitivity, specificity, positive predictive value, and negative predictive value were 96.9, 98.8, 95.8, and 99.2%, respectively. The agreement between the 2 cutoff points was excellent, and the kappa value was 0.954.
CONCLUSIONS: FEV1/FEV6 <0.72 can be used in primary care as a valid alternative to FEV1/FVC <0.70 as a fixed cutoff point for the detection of COPD in adults. This study suggests that FEV1/FEV6 is an effective and well validated option that should be used in primary care to detect COPD, which is a rampant problem.
Introduction
COPD is characterized by a decrease in air flow and shortness of breath. It has been shown that about 15% of United States adults age 40–79 have some form of COPD.1 Common types of obstructive lung diseases include COPD, chronic bronchitis, and asthma. The cause of about 90% of air flow limitation is COPD for adults without a diagnosis of asthma.2 It is estimated that COPD will be the third leading cause of death by 2020.3–6 Its prevalence and consequent burden is rising rapidly with high smoking rates in developing countries. Moreover, an aging population with these factors accounts for the actual and forecasted rapid growth in COPD.
Spirometry is the most frequently used pulmonary function test and is the fundamental tool for the screening, diagnosis, and follow-up of COPD in primary care, but the diagnostic standard for COPD is still debated. The use of reference equations, derived from a representative sample of healthy subjects, to determine lower limits of normal is recommended by the American Thoracic Society and the European Respiratory Society guidelines.7,8 Presently, spirometers, and in particular handheld spirometers, still do not provide reference equation-based lower limits of normal. Thus, it is difficult for the primary care practitioner to diagnose COPD.
To date, it is common practice to determine COPD by use of a fixed cutoff point, FEV1/FVC <0.70, according to the guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD).9 This definition is widely accepted, mainly because of its practicability.
In developing countries, due to a lack of trained technicians who can effectively assess FVC with costly spirometers in primary care, any less expensive alternative method would be highly desirable. Increasing evidence shows that FEV6 can be used as a convenient alternative to FVC.10–14 The use of 6-s expiratory maneuvers makes handheld spirometry faster and easier, provides a more explicit end-of-test definition, and reduces spirometry complications (such as syncope).15 However, reference equations for FEV6 and FEV1/FEV6 have been developed from the third National Health and Nutrition Examination Survey database and are only available for the United States population.16 As a developing country, China has a population of different age, race, height, and weight. It is necessary to develop the value of FEV1/FEV6 suitable for the Chinese population. The aim of this study is to determine an alternative to the fixed cutoff point of FEV1/FVC <0.70 suitable for FEV1/FEV6 in primary care.
QUICK LOOK
Current knowledge
COPD is commonly defined using a fixed cutoff point, FEV1/FVC <0.70, based on the guidelines from the Global Initiative for Chronic Obstructive Lung Disease. These measurements are typically made in the pulmonary function laboratory adhering to American Thoracic Society standards.
What this paper contributes to our knowledge
In a group of nearly 800 subjects, FEV1/FEV6 <0.72 was capable of being used in primary care as a valid alternative to FEV1/FVC <0.70 for the detection of COPD in adults. This study suggests that FEV1/FEV6 is an effective option that could be used in primary care to detect COPD.
Methods
Subjects
Xi'an is divided into 4 districts according to administrative region: North, East, South, and West. Two communities in each district were selected to be analyzed. The participants were between 18 and 80 y old and were residing in their current community for at least 2 years. Participants provided informed consent and pulmonary function test evaluation between July and August 2012. This study was approved by the ethics committee of the First Affiliated Hospital of Xi'an Medical University.
Definition of COPD
COPD is defined as: FEV1 <80% predicted; FVC normal or reduced, usually to a lesser degree than FEV1; and FEV1/FVC <0.70.9 All predicted values were based on the Knutson prediction model.
Pulmonary Function Test
FVC, FEV1, and FEV6 were measured by portable spirometer (Spirobank, GTM, Medical International Research, Rome Italy). Participants underwent 3 FVC maneuvers, and the maneuver with the best FEV1 was retained. Efforts that were incomplete or in which the participant coughed were excluded. Pulmonary function tests were performed by highly trained and experienced pulmonary function respiratory therapists, according to the guidelines of the European Respiratory Society.8
Statistics
The data were analyzed using JMPTM 10 (SAS, Cary, North Carolina) and GraphPad Prism 5.0 (GraphPad Software, San Diego, California). The chi-square test or Fisher exact test was used for the analysis of categorical variables. Analysis of variance was utilized to compare measurement variables. The receiver operating characteristic curves that corresponded to the optimal combination of sensitivity and specificity for FEV1/FEV6 were determined. The kappa test was used to compare the agreement between FEV1/FVC and FEV1/FEV6. We also calculated the positive predictive value and negative predictive value. Results are reported as mean ± SD, and P <.05 was considered statistically significant.
Results
Spirometric data from 767 subjects were studied, of whom 297 were male and 470 were female. Subjects' characteristics are shown in Table 1. In this table, FEV1/FVC <0.70 was used for the diagnosis of COPD. For the analyzed cohort, the average age was 58.2 ± 15.6 y. Of these participants, 164 subjects (21.4%) were diagnosed by the GOLD standard. The prevalence of cigarette smoking was 49.8% among men and 4.0% among women.
Summary Statistics and Comparison of Characteristics Between Sexes
Considering FEV1/FVC <0.70 as the accepted standard for COPD diagnosis, a receiver operating characteristic curve was utilized to determine the best corresponding cutoff for FEV1/FEV6 (Fig. 1). The area under the receiver operating characteristic curve was 98% (P < .001). The 0.72 of FEV1/FEV6 cutoff represented the greatest combination of sensitivity and specificity. For the total population in this study, the FEV1/FEV6 sensitivity was 96.9%, and specificity was 98.8%. The positive predictive value of FEV1/FEV6 was 95.8%, and the negative predictive value was 99.2%.
Receiver operator characteristic curve for FEV1/FEV6 using FEV1/FVC <0.70 as the preferred standard for COPD. The diagonal line represents the optimal combination of sensitivity and specificity.
When using an FEV1/FEV6 cutoff of 0.74, sensitivity reached 100%, but specificity dropped to 90% (positive predictive value = 82.2%, negative predictive value = 100%). Choosing a fixed cutoff of FEV1/FEV6 of 0.70 resulted in a specificity of 100% with a sensitivity of 84.0% (positive predictive value = 100%, negative predictive value = 75.2%). Multilevel likelihood ratios were constructed in Table 2.
Multilevel Likelihood Ratios for FEV1/FEV6 as a Marker for COPD
The spirometry test results for 12 participants were classified differently by the 2 methods, and all of them had observed values close to the lower limits of normal (Table 3). Analysis of the 12 discordant cases showed that 98.5% of the discordant values of FEV1/FEV6 were within a ±5% interval of the chosen fixed cutoff of 0.72. Overall agreement between the 2 criterion was excellent, and the kappa value was 0.954.
Comparison of FEV1/FEV6 With FEV1/FVC for the Diagnosis of COPD
Discussion
Obtaining 99% of the FVC in 6.64 s is sufficient and FEV6 is obtained in >80% of tests. Moreover, the spirometric maneuver for FEV6 is performed easily, and it satisfies the standard for repeatability and diagnostic accuracy.17 Thus, FEV6 could be a valid alternative to FVC for the diagnosis of COPD in primary care. The main purpose of the present study is to determine a fixed cutoff for the FEV1/FEV6 ratio that is equivalent to the commonly used fixed cutoff of FEV1/FVC <0.70. Our study demonstrates that FEV1/FEV6 <0.72 can be considered as a valid alternative to FEV1/FVC <0.70, and it is possible to detect COPD as a fixed cutoff point for primary care in adults.
The use of FEV1 and FEV1/FVC ratio seems to have become the predominant, if not the unique, factor for determining the presence of COPD. Reduced FEV1/FVC provides a powerful and reliable judgment for COPD, but clinicians have recognized its limitations for quite a while. The most obvious one is that diagnosis of COPD in elderly people will be falsely elevated.18,19 This is the main reason driving the interest in FEV6 and the FEV1/FEV6 ratio. Additionally, the use of FEV1/FVC is more time-consuming and more expensive than the use of FEV1/FEV6, FVC-based portable spirometers generally costing $700 to $1,000, compared with only $60 to $80 for FEV1/FEV6 instruments. Therefore, it is an ideal method for objectively diagnosing and following up respiratory diseases in busy primary care centers. Indeed, with a receiver operating characteristic (area under the curve) value of 0.98, excellent overall performance was obtained for FEV1/FEV6 <0.72 as a fixed cutoff for the detection of COPD. The following as standards are used to classify the accuracy of a diagnostic test: 0.9–1 = excellent, 0.8–0.9 = good, 0.7–0.8 = fair, 0.6–0.7 = poor, 0.5–0.6 = fail.
Other studies showed similar cutoff points (0.73 and 0.75) of the FEV1/FEV6 ratio to detect COPD, both using the fixed FEV1/FVC <0.70 for comparison. Melbye et al20 used a spirometry database of referenced subjects from a medical facility, whereas subjects from a highly homogeneous population-based sample in a northern city of Norway were recruited in the study by Vandevoorde et al.21 A fixed cutoff of 0.75 was obtained from healthy adults in PLATINO studies.22 In our study, the volunteers are from local communities, and this can reflect actual lung function. Despite the different population backgrounds among these studies, a similar cutoff point for the FEV1/FEV6 ratio was obtained.
A fixed cutoff point for FEV1/FEV6 is an effective method for the diagnosis of COPD, but certain disadvantages have to be taken into account. One, for example, is that FEV6, like FVC, was easily affected by sex and by education level.17 In addition, there is potential misclassification for elderly subjects, where the age-related decline in FEV1/FVC and FEV1/FEV6 may cause a significant overdiagnosis of COPD.18 FEV1 is also vulnerable to the impact of smoking and ambient air pollution.23,24 Therefore, the fixed ration of FEV1/FEV6 for diagnosis of COPD also should be interpreted in the context of the patient's risk factors, age, and symptoms. However, the merit of using a fixed cutoff value for the FEV1/FEV6 instead of a reference equation to diagnose COPD is still highlighted by the COPD guidelines.9
This study has some limitations due to its cross-sectional design. Our results are more suitable for this region of China. In addition, the sample size is small for a survey of lung function. A study with a larger sample size would provide more data and enhance the generalizability of the findings.
Conclusion
Our results demonstrate that FEV1/FEV6 <0.72 can be used in primary care as a valid alternative to FEV1/FVC <0.70 as a fixed cutoff point for the detection of COPD in adults. This study suggests that FEV1/FEV6 is an effective and well validated option that should be used in primary care to detect COPD, which is a rampant problem.
Acknowledgment
We thank the study participants and research personnel for involvement in the study.
Footnotes
- Correspondence: Shengyu Wang MD, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077 China. E-mail: wangshengyu{at}yeah.net.
This work was supported by Education Department of Shaanxi Provincial Government Grant 11JK0707. The authors have disclosed no conflicts of interest.
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