Comparison of the Prevalence of Chronic Obstructive Pulmonary Disease Diagnosed by Lower Limit of Normal and Fixed Ratio Criteria

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is not fully reversible. COPD is a leading cause of morbidity and mortality worldwide and is the only major disease that is continuing to increase in both prevalence and mortality (1-4). Since early detection and intervention is currently the best approach to reduce the economic and social burden of COPD, there has been a call for global strategies to assess the prevalence of COPD (5).

Spirometry is essential for diagnosis in COPD. The ratio of forced expiratory volume in one second (FEV₁) to forced vital capacity (FVC) is an acceptable indicator of the presence of airflow limitation. Unfortunately, there was no consensus on diagnostic criteria of COPD, every guidelines used their own diagnostic criteria recently (6-9). After the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was introduced in 2001, specific spirometric cut-point (e.g., post-bronchodilator FEV₁/FVC <0.7) has been used for diagnosing COPD (1, 10).

A nationwide COPD prevalence survey in Korea in conjunction with the second Korean National Health and Nutrition Examination Survey (Korean NHANES II) was conducted from 2001 to 2002. Using GOLD criterion for defining airflow limitation, 17.2% of Korean adults over the age of 45 yr had COPD and most of them had mild disease (11).

However, the FEV₁/FVC ratio decreases with age because the FEV₁ declines more rapidly with age than the FVC in normal subjects, so the FEV₁ percentage of predicted will decrease with age because of the shrinking denominator of the percentage of predicted index. Therefore, it is suggested that the use of fixed ratio may result in over-diagnosis of COPD in the elderly, especially with mild disease (12).

The Korean COPD prevalence survey showed that 35.0% of adults over the age of 65 yr and 41.4% over the age of 70 yr (11) proved to have COPD. Even though more than half of them belonged to mild degree of COPD, the figure seemed to be over-exaggerated in elderly. Therefore, we need to apply a new criterion to correct overwhelming higher prevalence of COPD in senior citizens. The lower limit of normal (LLN), based on the normal distribution, classify the bottom 5% of the healthy population as abnormal. When we use LLN criterion in the evaluation of FEV₁/FVC, it could be one of alternatives to minimize the potential misclassification (1, 13). The objective of this study was to compare the prevalence of COPD by using fixed ratio and LLN of FEV₁/FVC for the presence of airflow limitation.

This study was preformed as a part of a nationwide COPD prevalence survey. It was conducted in conjunction with the second Korean National Health and Nutrition Examination Survey (Korean NHANES II) from October 15, 2001 to January 20, 2002. Spirometry was performed by specially trained technicians who conformed to the 1994 American Thoracic Society (ATS) recommendations (11, 14). In 2005, ATS and European Respiratory Society (ERS) published a new statement on spirometry that changed the repeatability criteria (the difference between the largest and the next largest FEV₁) from ≤0.2 L to ≤0.15 L (15). So the acceptability and repeatability criteria of the spirometry in this study were adopted from the 2005 new ATS/ERS recommendations (15). A more detailed description of the nationwide COPD survey methodology and spirometric procedures has been previously published (11, 14).

New predictive equation for FEV₁/FVC and LLN of the FEV₁/FVC

A new prediction equation for FEV₁/FVC was made by linear regression analysis. The variables affecting the normal predicted values of the FEV₁/FVC for male and female were age and height. The new prediction equations were 125.77628-0.36304×age (yr)-0.17146×height (cm) for Koreans male and 97.36197-0.26015×age (yr)-0.01861×height (cm) for Koreans female.

The observed values of FEV₁/FVC were distributed normally, so the lower limits of the normal range (LLN) for FEV₁/FVC were calculated for each subject using the new reference equations. These were based on the predicted value minus 1.645-times the standard error of the estimate (SEE) (16, 17) (Table 1).

Table 1
New prediction equation of FEV₁/FVC%^* in adult Koreans

• Click for larger image

We analyzed 2,728 subjects who met new spirometry criteria for acceptability and repeatability from Korean national COPD survey. The age adjusted prevalence rate of COPD in the general population of Korea varies, according to the criterion used for its definition, from 10.9% with LLN criterion to 15.5% with fixed ratio criterion.

The ATS/ERS recently revised their spirometry recommendations, which included changes in spirometry acceptability and repeatability criteria (15). As the Korean NHANES II used the previous the ATS spirometry recommendations (16), we did not use the prediction equation that derived from Korean NHANES II (14). Instead, we made a new prediction equation for FEV₁/FVC. The mean differences between the predictive values of our new equation and other equations including the equation from the Korean NHANES II (14, 18-21) were about 1%, therefore it was reasonable to use our new equation.

There were 146 subjects who were differently classified according to each criterion. The discrepancy rate was 5.35% of the study population. This discrepancy rate was greater in older age groups and more prominent as age increased. And, there was different pattern of discrepancy according to age groups. For the younger subjects, more subjects were classified with airflow limitation by the LLN criterion. Contrarily, more subjects were classified with airflow limitation by fixed ratio criterion for the older subjects. These results implied that use of LLN may reduce the prevalence of COPD in elderly.

We previously reported 17.2% of the prevalence rate of COPD from the same nationwide COPD survey. But our previous study was performed based on the 1991 ATS spirometry recommendations and analyzed subjective who underwent at least two spirometry measurements acceptable by the 1991 ATS criteria (11). Our present study reselected study population according to the new ATS/ERS spirometry recommendations for the acceptability and repeatability (15). The crude prevalence rate of airflow limitation in the present study was lower than that of our previous study in subjects aged 45 or more. The prevalence rate of COPD by the fixed ratio criterion of the present study was 15.5%, which was lower than previous results (11). This meant that use of more strict criteria for spirometry also may reduce the prevalence rate of COPD in the elderly.

Since there had been no consensus on the criteria for diagnosis of COPD recently, a majority of national guidelines had their own diagnostic criteria of COPD (6-9, 23). The prevalence rate of COPD population depends on the criterion for the definition of airflow limitation even in the same population (24). After the GOLD guideline was introduced in 2001, a consensus of the diagnostic criterion of COPD was made; FEV₁/FVC <0.7 (1, 11). But the definition of an obstructive pulmonary defect given in the recently published ATS/ERS spirometry recommendations contrasts with the definition suggested by the GOLD and ATS/ERS guidelines, in that FEV₁ is referred to vital capacity (VC) rather than just FVC and the cut-off value of this ratio is set at the 5th percentile of the normal distribution rather than at a fixed ratio of 0.7. The advantage of using VC in place of FVC is that the ratio of FEV₁ to VC is capable of accurately identifying more obstructive patterns than its ratio to FVC, because FVC is more dependent on flow and volume histories (13).

There were few studies comparing the lower limit of normal (LLN) to fixed ratio for the detection of airflow limitation to diagnose COPD. Our present study showed that use of LLN criterion for the diagnosis of COPD decreased the prevalence rate as much as 4.6% for the subject with aged ≥45 yr. This result corresponds with the earlier study by Celli et al., which evaluated the impact of five different definitions of airflow limitation on the estimated prevalence of COPD (17). Our study also showed that 27 subjects (14.3%) with airflow limitation by fixed ratio criterion did not show airflow limitation by LLN criterion for subjects of age 65 or older. This figure was comparable to that of recent study by Hansen et al. which reported that using fixed ratio criterion misidentified 11.3% of subject of age seventh and eighth decade as abnormal (25). But in contrary to our study, both studies used the 1994 ATS spirometry recommendations. We believe this study to be the only one which adopted new 2005 ATS/ERS spirometry recommendations to date.

This study has some limitations though. The spirometric definitions of COPD generally require post-bronchodilator measurement (1, 10), but the spirometry examination in this nationwide survey did not include a test of reversibility of obstruction. While some subset of the study population had probability of having pure asthma, we believe the prevalence figure of airflow limitation is reasonable as a criterion of the prevalence of COPD especially after the age of 45 yr in this large epidemiologic survey. We understand that the reference equations using post-bronchodilator measurement of lung parameter are not validated (1, 26). The other limitation is that we did not use the LLN of the vital capacity (VC) recommended by the ATS/ERS to differentiate the pure obstructive defect from the mixed defect (13). The FVC is usually reduced more than IVC (inspiratory vital capacity) or SVC (slow vital capacity) in airflow obstruction (27). However, the effect of these differences on population estimates has not been studied (17). So the ratio of forced expiratory volume in one second (FEV₁) to forced vital capacity (FVC) seemed to be reasonable indicator of the presence of the airflow limitation in this large epidemiologic survey.

Our study found that 10.9% of Korean adults over the age of 45 yr had COPD by LLN criterion, which reduced the prevalence rate of COPD by 4.6% point. More strict application of spirometry criteria for acceptability and repeatability also reduced the prevalence of COPD.

In conclusion, adopting LLN and more strict spirometry criteria revealed lower prevalence rate of COPD in elderly Korean population. Particularly, using LLN criterion might reduce the risk of over-diagnosis of COPD in the elderly.