American Journal of Respiratory and Critical Care Medicine

With many epidemiologic studies made to establish the prevalence of sleep-disordered breathing (SDB) and obstructive sleep apnea syndrome (OSAS) in Western countries, no such data have been reported in Korea. The purpose of this study was to examine the prevalence of SDB and OSAS, and their related factors in Korean adults aged 40–69 years. Among the total of 5,020 participants at the baseline examination of the Korean Health and Genome Study, a random sample of 457 men and women was studied with employment of overnight full polysomnography to determine the prevalence of SDB and OSAS. The prevalence of SDB (apnea–hypopnea index ⩾ 5) was 27% and 16% in men and women, respectively. When OSAS was defined by an apnea–hypopnea index ⩾ 5 plus excessive daytime sleepiness, its prevalence was 4.5% in men and 3.2% in women. Logistic regression analyses showed that sex, body mass index, and hypertension were closely associated with the risk of SDB. Our findings show that SDB is a common problem in the Korean adult population. Understanding and treatment of SDB may be essential in terms of intervention to reduce the risk of related medical problems.

Sleep-disordered breathing (SDB) has been well known to be a common syndrome (1, 2), and to be associated with various medical problems (37) that have impact on morbidity and mortality, causing an additional burden of the public health service (810). There have been many epidemiologic studies to establish the prevalence of SDB and obstructive sleep apnea syndrome (OSAS) in Western countries (1, 2, 1113), with limited data having been published in Asian countries (1416). Previous studies reported that the prevalence of SDB ranged from 3 to 28% in western countries, depending on the definition of SDB and the methodology of the studies. Recently, among Asians, the prevalence of SDB was estimated to be 8.8% in Chinese office men (15) and 19.5% in normal Indian men (16). Interestingly, obesity appeared to be a common and important risk factor for SDB throughout all the previous studies.

To our knowledge, the prevalence of SDB, by using the full polysomnography (PSG), in both men and women of the Korean population has not been reported so far. Therefore, the purpose of this study was to estimate the prevalence of SDB and OSAS and to determine the related factors, such as anthropometric measurements and clinical features, in connection with SDB among Korean adults aged 40 to 69 years.

Sample

The Korean Health and Genome Study (KHGS) began in 2001 as an ongoing population-based study of Korean adults aged 40 to 69 years. Participants of the study included residents of Ansan community, 32 km southwest of Seoul. A two-stage sampling scheme was designed to optimize the precision of the study through oversampling of the subjects who were more likely to have SDB and to construct a cohort representing a wide range of SDB. In the first stage, 2,523 men and 2,497 women accomplished the baseline examination at the research center. Each participant of the study received a set of thorough questions pertaining to demographic characteristics, sleep habits, and related problems posed by a trained interviewer. In the second stage, 5,020 participants were assigned to one of the two groups, based on the presence or absence of habitual snoring. Among them, 50% of habitual snorers and 10% of nonhabitual snorers were randomly selected and recruited by telephone to take part in the following stage of the study. Habitual snoring was defined as a snoring frequency ⩾ 4 days per week; snoring with less frequency was defined as nonhabitual snoring.

Polysomnography

Among the total of 472 subjects, 137 subjects underwent PSG at their homes, and the others at the sleep laboratory with a computerized PSG device (Alice 4; Respironics, Atlanta, GA). This device makes it possible to carry out an examination both at home and at the sleep laboratory setting. Sixteen channels were used to document the following parameters: four channel electroencephalogram, electrooculogram, submental and leg electromyogram, ECG, airflow at the nose and mouth (thermisters), the chest and abdominal respiratory movement, oxygen saturation (pulse oximetry), snoring microphone, and the body position. All the PSG results were manually scored according to the standard criteria (17). Arousals were also identified according to the established criteria (18). Apnea was defined as absence of the airflow for 10 seconds, and hypopnea was defined as a discernible reduction of the airflow associated with reduction of oxygen saturation by 4% from the baseline. The apnea–hypopnea index (AHI) was defined as the average number of apneic and hypneic events per sleep hour. Excessive daytime sleepiness (EDS) was subjectively assessed with three questions based on the five-point scale. The response was considered positive if the score was three or more. The subjects were identified as demonstrating an EDS if they answered in the affirmative two or more of these three questions. SDB was defined as AHI ⩾ 5 and OSAS as SDB with EDS. Hypertension was diagnosed when either the systolic or diastolic blood pressure was ⩾ 140/90 mm Hg, respectively, or when the study participant received an antihypertensive medication.

Statistical Analysis

The data are presented as means ± SD for continuous variables and as percentages for categorical variables. Comparison between the groups was done with the t test for continuous variables and chi-square test for discrete variables. Logistic regression models were applied to identify the overall and independent factors in relation to SDB. All analysis was done with SPSS (Chicago, IL) version 10.0 for Windows.

Characteristics of Study Sample

This study was made as a part (Ansan city) of KHGS. The total of 472 subjects underwent the overnight sleep study (response rate 55%). The subjects who consented to PSG and those who refused to PSG among habitual snorers and nonhabitual snorers were of no significant difference with respect to the personal data (age, anthropometric measurements, and sleep characteristics, p > 0.05). PSG were done in the laboratory or home settings, depending on convenience and cooperation of the participants. In the pilot study for the comparison of the results from the laboratory PSG with those from the home PSG, the mean values of AHI were not significantly different (9.3 ± 12.7 vs. 7.8 ± 12.3, respectively, p > 0.05).

Table 1

TABLE 1. General characteristics of the study population



Men

Women
Habitual SnorersNonhabitual SnorersHabitual SnorersNonhabitual snorers

(n = 554)
(n = 1,969)
(n = 314)
(n = 2,183)
Age, yr49.1 ± 7.448.4 ± 7.454.3 ± 8.3§48.8 ± 7.9
Current smoker, %48.943.53.8 3.0
BMI, m2/kg25.6 ± 2.8§24.3 ± 2.626.6 ± 3.3§24.5 ± 3.0
WHR 0.88 ± 0.05§ 0.86 ± 0.05 0.85 ± 0.06§ 0.81 ± 0.09
Hypertension, %*37.0§25.538.9§19.9
SDB-related problems
 Morning headache 9.9 7.220.414.2
 Witnessed apneic events57.4§12.420.7§ 2.3
 Awakening due to breathing pause
 9.7§
 3.4
 8.0
 4.1

*Hypertension was defined as a self-reported use of antihypertensive medication, or systolic or diastolic blood pressure ⩾ 140 and 90 mm Hg, respectively.

Data expressed as means ± SD.

Significantly different from nonhabitual snorers (p < 0.05).

§Significantly different from nonhabitual snorers (p < 0.001).

Significantly different from nonhabitual snorers (p < 0.01).

Definition of abbreviations: BMI = body mass index; SDB = sleep-disordered breathing; WHR = waist–hip ratio.

shows the general characteristics of the study subjects between the habitual snorer and the nonhabitual snorer by sex. The mean age was 49.1 and 48.4 years in men with and without habitual snoring, respectively, and 54.3 and 48.8 years in women. The prevalence of the habitual snoring was significantly higher in men than in women (21.9% vs. 12.5%, respectively, p < 0.001). Both habitual snorers and nonhabitual snorers showed significant differences in the waist–hip ratio (WHR), body mass index (BMI), and SDB-related problems. In addition, the prevalence of hypertension was significantly higher in habitual snorers than in nonhabitual snorers in both men and women (men: 37.0 vs. 25.5%, p < 0.001; women: 38.9 vs. 19.9%, respectively, p < 0.001).

Polysomnographic Data and Spectrum of Severity of SDB

Table 2

TABLE 2. Demographic and polysomnographic data, and symptoms in study subjects



Men (n = 309)

Women (n = 148)

AHI ⩾ 5
AHI < 5
AHI ⩾ 5
AHI < 5
Age, yr49.6 ± 7.748.3 ± 8.1 55.8 ± 10.249.5 ± 8.5
BMI, kg/m226.5 ± 2.924.7 ± 2.626.9 ± 4.124.3 ± 3.1
WHR 0.89 ± 0.05§ 0.88 ± 0.05 0.86 ± 0.08§ 0.83 ± 0.07
Systolic BP, mm Hg124.3 ± 17.3117.9 ± 15.4121.0 ± 16.4§113.1 ± 17.1
Diastolic BP, mm Hg 84.4 ± 10.9 79.4 ± 11.877.2 ± 9.9 74.2 ± 11.3
LDP, %81.3 ± 6.190.5 ± 3.483.7 ± 3.8 89.6 ± 12.3
AHI, events/h 20.6 ± 17.4 1.4 ± 1.310.3 ± 7.31.05 ± 1.1
Arousal index 23.6 ± 14.2 14.1 ± 10.014.7 ± 10.1 9.1 ± 8.4
SDB-related symptoms, %
 EDS*16.214.026.723.7
 Reported habitual snoring81.5 3.050.0§24.6
 Witnessed apneic events
60.0
25.7
23.3
 5.9

*EDS was identified as two positive in response to three subjective questionnaires.

Data expressed as means ± SD.

Significantly different from those with AHI < 5 (p < 0.001).

§Significantly different from those with AHI < 5 (p < 0.05).

Significantly different from those with AHI < 5 (p < 0.01).

Definition of abbreviations: AHI = apnea–hypopnea index; BMI = body mass index; EDS = excessive daytime sleepiness; LDP = lowest desaturation point; SDB = sleep-disordered breathing; WHR = waist–hip ratio.

shows the difference of polysomnographic, demographic, and anthropometric data between those with AHI ⩾ 5 and with AHI < 5 by sex. WHR, BMI, and systolic blood pressure were significantly higher in those with AHI ⩾ 5 than those with AHI < 5 in both men and women. Distribution of habitual snoring and reported apneic events assessed by the questionnaire were also significantly different between those with AHI ⩾ 5 and those with AHI < 5 (p < 0.001), whereas EDS was of no significant difference.

Prevalence of SDB and OSAS

Among the 457 subjects who underwent PSG, 130 men (42%) and 30 women (20%) were found to have AHI ⩾ 5. The prevalence of SDB at the three cutoff points of AHI (AHI ⩾ 5, ⩾ 10, ⩾ 15) was extrapolated on the basis of the study population (Table 3)

TABLE 3. Age-specific prevalence of sleep-disordered breathing using various cutoff points for apnea–hypopnea index




Prevalence, % (95% CI)

Subjects (%)
AHI ⩾ 5
AHI ⩾ 10
AHI ⩾ 15
Men, yr
 40–491,660 (65.7)24.2 (21.4–27.2)17.3 (14.6–19.9) 9.5 (6.8–12.2)
 50–59 570 (22.6)33.7 (28.8–38.8)21.6 (17.6–25.8)11.9 (4.2–12.5)
 60–69 293 (11.7)29.9 (23.4–36.3)22.0 (15.3–28.8)10.8 (4.1–17.5)
 Total2,523 (100)27.1 (24.7–29.4)18.9 (16.9–21.2)10.1 (8.0–12.3)
Women, yr
 40–491,491 (59.7)8.2 (9.0–14.3)4.1 (3.8–7.8)2.9 (0.8–4.9)
 50–59 582 (23.4)25.2 (21.5–31.6)10.0 (6.5–13.6)2.9 (0.1–6.4)
 60–69 424 (16.9)28.6 (22.5–34.8)9.5 (5.3–13.8) 9.5 (5.3–13.8)
 Total
2,497 (100)
16.8 (14.5–19.2)
6.7 (5.1–8.3)
4.7 (3.1–6.4)

Definition of abbreviations: AHI = apnea–hypopnea index; 95% CI = 95% confidence interval.

. The prevalence of SDB (AHI ⩾ 5) was 27.1% and 16.8% in men and women, respectively. The prevalence of SDB, by using the cutoffs of ⩾ 10 and ⩾ 15, was 18.9 and 10.1% in men, and 6.7 and 4.7% in women, respectively. The prevalence of OSAS defined by AHI ⩾ 5 plus EDS was 4.5% in men and 3.2% in women. As shown in Table 3, men aged 50 to 59 years had the highest prevalence of SDB in both AHI ⩾ 5 and AHI ⩾ 15 than any other age group. On the other hand, the prevalence of SDB in women increased with age.

Factors Associated with SDB

Crude and adjusted odds ratios for the logistic regression model presenting non-SDB and SDB are shown in Table 4

TABLE 4. Risk factors for sleep-disordered breathing in the study population|




Odds ratio (95% CI)
Characteristics
Comparison groups
Crude
Adjusted||
SexMen vs. women2.85 (1.80–4.52)2.50 (1.44–4.34)
Smoking statusYes vs. no1.61 (1.03–2.53)§1.01 (0.62–1.67)
Alcohol statusYes vs. no1.92 (1.29–2.85)1.37 (0.85–2.21)
BMI*2nd vs.1st tertile2.72 (1.58–4.68)2.33 (1.32–4.10)
3rd vs.1st tertile4.54 (2.67–7.73)3.96 (2.27–6.91)
Hypertension
Present vs. absent
2.05 (1.35–3.11)
1.54 (1.12–2.41)§

*BMI was divided by tertile of subject (cutoff value of the highest and lowest tertile were 24.0 and 27.0 kg/m2, respectively).

Hypertension was defined as the self-reported use of antihypertensive medication, or systolic or diastolic blood pressure ⩾ 140 and 90 mm Hg, respectively.

p < 0.001.

§p < 0.05.

p < 0.01.

|| Adjusted for age and significant variables in the univariate model.

. Sex, smoking and alcohol consumption, BMI, and hypertension were closely associated with an increased risk of SDB in the univariate model. However, smoking and alcohol consumption were not significantly related to SDB after adjustment for the confounding factors. After adjustment for age and significant variables in the univariate model, sex (men vs. women, odds ratio [OR]: 2.50, p < 0.05), BMI (2nd and 3rd tertile vs. 1st tertile, OR: 2.33 [p < 0.01] and 3.96 [p < 0.001], respectively), and hypertension (present vs. absent, OR: 1.54, p < 0.05) were identified as factors independently associated with SDB.

This study demonstrates that SDB is prevalent in the Korean general population, as it is in other countries (1, 2, 1116). Our study is the first report on the prevalence of SDB and OSAS in the Korean population, based on a full PSG documentation, which is proposed as the gold standard for the diagnosis of SDB. Although the ideal design of the study should include PSG with respect to all the participants in the assessment of SDB and OSAS, this was extremely difficult to do, because the diagnostic test itself is time-consuming for the subjects and expensive for the investigators. In many epidemiologic studies on the prevalence of SDB (1, 15, 16, 19), at least a two-stage sampling method was performed, in which a portion of the population was screened with questionnaires or portable diagnostic devices, and then these results were extrapolated on the basis of the general population. As in previous studies, the two-stage method was also applied to estimate the prevalence of SDB and OSAS in this study. As a result, our study showed that the prevalence of SDB was 27% and 16% in both men and women aged 40 to 69 years, respectively. The prevalence of OSAS (AHI ⩾ 5 plus EDS) was found to be 4.5% in men and 3.2% in women.

This study had a limitation in estimating the prevalence of SDB and OSA. The sampling method may have a potential selection bias, which is common in a large-scale epidemiologic study when subjects are selected from a large population. In this study, 1,474 subjects (24.7%) of nonparticipants (n = 5,955) did complete five simple health-related questions. The participants, compared with the nonparticipants, were marginally less likely to be smokers and more likely to have hypertension (p < 0.05), although this information was limited. Unfortunately, we did not acquire the additional information (body habits and sleep problems, etc.). Our estimated prevalence of SDB and OSAS may have been affected by this bias. However, whether this prevalence was overestimated or underestimated could not be fully assessed. Moreover, the mean BMI, which has been known to be a reliable predictor of SDB, was 24.6 ± 2.7 and 24.7 ± 3.1 kg/m2 in men and women, respectively. These values were similar to those of the Korean adult population (20, 21). Thus, the prevalence rate of our study would be representative of the general population in Korea.

In the Wisconsin study (1), Young and coworkers have reported that the prevalence of SDB, using similar criteria to ours, is estimated to be 24 and 9% in 30- to 60-year-old men and women, respectively, and OSAS defined by AHI ⩾ 5 plus daytime sleepiness occurred in 4 and 2% of men and women, respectively. In the Busselton Health Survey (2), Bearpark and colleagues have described that 26 and 3% of men aged 40 to 65 years had SDB and OSAS, respectively, using a similar definition as our study. Duran and coworkers (19) found that the prevalence of SDB using a definition of AHI ⩾ 5 was 26 and 28% in Spanish men and women, respectively. Our results are consistent with those of previous Western studies, in spite of the difference in the prevalence of obesity, a strong risk factor for SDB, being relatively uncommon in Asian countries.

Recently, several studies on the prevalence of SDB have been conducted in Asian countries. However, the documentation of the prevalence of SDB using the full PSG for the diagnostic test, taking into account the fact that it is also too expensive for the investigators in developing Asian countries, is inadequate and fragmentary. Most of these studies are based on the symptoms addressed by the questionnaire (14), portable monitoring device (22), or noted in cohorts consisting of subjects with medical problems (23). Recently, two studies on the prevalence of SDB and OSAS have been reported in Asian countries. Ip and coworkers (15, 24) were the first to estimate that the prevalence of SDB and OSAS using full PSG was 8.1 and 4.1% in Chinese men aged 30 to 60 years, and 3.7 and 2.7% in women of the same age group, respectively. Moreover, Udwadia and colleagues (16) have reported that the prevalence of SDB and OSAS employing a limited PSG in urban Indian men aged 35 to 65 years were 19.5 and 7.5%, respectively. When our results are compared with those of the previous two studies, the prevalence of SDB in our study shows the highest rate. On the other hand, the prevalence of OSAS (AHI ⩾ 5 with EDS) was similar to that of the Chinese study. Although it is not explicitly stated, a possible reason for a higher prevalence of SDB in our study compared with the Chinese and Indian studies may be partially due to the difference in the methodology applied. In several early studies, the study subjects were selected among the inpatient population (25, 26) where a higher prevalence of SDB can be expected. On the other hand, because others have used working population and volunteers (1, 27, 28), from which results probably reflect the inclusion of more healthy individuals, lower prevalence may have been obtained than can be expected in a random selection of subjects from the general population. Therefore, it is likely that our results from a random sample of the general population show a higher prevalence rate compared with that of the Chinese and Indian studies using volunteers and normal subjects visiting hospital for routine health check or insurance reasons.

In our study, EDS assessed by subjective answers to three questions was found in 16.2% of men and 26.7% of women with AHI ⩾ 5, and in 14.0% of men and 23.7% of women with AHI < 5. Although subjects with SDB showed a higher rate of EDS than those without SDB in both men and women, it was of no statistical significance. The assessment concerning the symptoms of sleepiness is not an objective measurement, being based on the questionnaire to identify subjective feeling of sleepiness, and it may fail to reflect the physiologic state of sleepiness (29, 30). Although the American Academy of Sleep Medicine Task Force (31) proposed a consensus definition for OSAS based on an AHI ⩾ 5 plus presence of symptoms, it seems difficult to precisely define OSAS, according to a low AHI score and EDS in the general population.

We applied full PSG in two different places: the participants' homes and sleep laboratory, with the same device to increase convenience and cooperation of the participants, because the preselected subjects had refused to perform the laboratory PSG for reasons of the inconvenience associated with visiting the laboratory. Moreover, we compared the data from the home PSG with those from the laboratory PSG, without significant differences noted in respect of the respiratory events. Therefore, this variation between the home PSG and laboratory PSG data may be insufficient to interfere with identification of the presence of SDB in our study. In a previous study, Portier and colleagues (32) reported that there was no evidence of a better quality of the sleep and recording tolerance at home. Fry and coworkers (33) have also demonstrated that the polysomnographic data obtained in the home and laboratory settings showed no significant difference with respect to mean values of AHI. We have performed only a single-night PSG within this study. Several studies suggest that the night-to-night variability, such as difference in the posture and body position, medication, and nasal congestion, might have affected the detection of respiratory abnormalities (34, 35). However, there is little agreement about this difference. Some studies have shown that the initial and second laboratory studies fail to significantly differ (36, 37).

We have analyzed the factors with an independent relationship with SDB using the logistic regression models. After adjustment for the confounding factors, the sex, BMI, and presence of hypertension were found to be closely associated with SDB in our study (Table 4). Although alcohol consumption and smoking status were found to be directly related to SDB in the univariate model, this close association disappeared in the multivariate analysis. There is an increasingly convincing evidence that the sex difference in the prevalence of SDB is not so great as it has generally been believed. In most population-based studies that have estimated the gender-specific prevalence, a two- or threefold larger risk in men, compared with women, has been reported (9). Our results have also shown that males are more likely to have SDB (OR: 2.5, 95% CI: 1.4–4.3, p < 0.01) than females after adjustment for the related factors. The exact reason for the lower prevalence of SDB in women than in men has not been in full identified. Most hypotheses, to account for this disparity, focus on a role of the sex hormone (38) and difference in the structure of the upper airways (39) involved in the pathogenesis of SDB.

A close association between BMI and SDB in adults has also been noted in previous studies (1, 2, 1116). In our study, the top tertile of BMI (BMI ⩾ 27 kg/m2), which was over the cutoff point in respect of obesity in Asians (40), had a 3.9-fold excess with respect to the risk of SDB, as compared with the bottom tertile of BMI (BMI < 24 kg/m2). However, the prevalence of obesity, defined as Western cutoff (BMI ⩾ 30 kg/m2), is only 4.6% in our population. This percentage is lower than those of previous studies of Western countries (2, 41, 42). In addition, 35.2% of subjects with SDB had a BMI of more than 27 kg/m2, which is cutoff point in Asian for obesity. These finding suggest that a significant percentage of our subjects were not obese defined by Western or Asian criteria, but still had SDB. This led us to speculate that other risk factors, such as contents of body fat and anatomical structure of upper airway, may be responsible for our higher prevalence. Recently, obesity has become one of the social problems in Korea, and the major cause of the increasing obesity is known to be the change of lifestyle and nutrition associated with rapid economic growth and globalization processes (43). Consequently, the number of cases of SDB will increase over the next few decades in Korea. In previous studies, Bloom and colleagues (44) suggest that SDB may be related to reduction of the diameter of the pharyngeal airways due to deposits of the adipose tissue in obese individuals. Grunstein and coworkers (45) propose that the waist circumference could be a better predictor of sleep apnea than the neck circumference or BMI. In Asian studies (15, 16), Ip and coworkers and Udwadia and colleagues also have reported that higher BMI is a risk factor for SDB in Chinese and Indian subjects. These researchers, however, suggest that other strong risk factors rather than BMI are more prevalent in Asian countries as opposed to Western populations, such as craniofacial features that compromise the upper airways. Some, but not all, of the clinical observations concerning Asian patients with OSA support this suggestion (4648). However, more information about the etiologic factors of SDB in various ethnical groups is undeniably needed to understand the weight of SDB.

Although some studies show an independent association between snoring and hypertension (49, 50), others point out that this relationship may be explained by the confounding effects of age, obesity, and other potential factors (51, 52). In epidemiologic studies, however, there is a growing consensus that SDB is an important risk factor for hypertension regardless of the excessive weight and other potentially confounding factors. Carlson and coworkers (53) studied the relative influence of BMI and sleep apnea on the blood pressure and the prevalence of hypertension in 377 consecutive subjects referred to the sleep laboratory. Age, BMI, and sleep apnea were all found to be independent predictors of hypertension. Obesity combined with sleep apnea turned out to result in a 3.9-fold increase in the prevalence of hypertension. Nieto and colleagues (4) found a close association between AHI and hypertension in a cross-sectional sample of 6,132 men and women participated in the Sleep Heart Health Study. Moreover, in prospective analysis of the Wisconsin Sleep Cohort (3), even minimally elevated AHI at the baseline of the study was associated with a 42% increase in the odds of the developing hypertension over the 4-year follow-up period. A dose–response relationship was observed in more clearly expressed categories of AHI, with the odds ratio of 2.9 for AHI ⩾ 15 versus AHI of zero. In our study, SDB is independently associated with the presence of hypertension (OR: 1.54, 95%CI: 1.12–2.41, p < 0.05) after adjustment for confounding factors. Therefore, our results have confirmed a relationship between SDB and hypertension.

In summary, we have found out that the prevalence of SDB in the Korean population is a common problem, as it is in Western countries, in spite of a lower prevalence of obesity. Recently, due to changes in nutrition and dietary traditions associated with the economic growth in Korea (43), obesity has been a continuously increasing medical and dietary problem for the last few decades. In addition, obesity-related diseases, such as coronary heart disease and stroke, are major causes of death in Korea (54). Therefore, early detection and treatment of SDB may be essential in terms of intervention to reduce risk of associated medical problems. In this study, sex, higher BMI, and presence of hypertension were found to be predictive factors for presence of SDB.

The authors thank Dr. Lee and Dr. Joo for helping us with constructive advice.

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Correspondence and requests for reprints should be addressed to Chol Shin, M.D., Ph.D., Director, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, #516, Gojan-1-dong, Danwon-gu, Ansan-si, Gyeonggi-do, 425-707, South Korea. E-mail:

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