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Epidemiological survey of chronic obstructive pulmonary disease and alpha‐1 antitrypsin deficiency in Korea

2001; Wiley; Volume: 6; Issue: s2 Linguagem: Inglês

10.1046/j.1440-1843.2001.00305.x

1440-1843

Young‐Soo Shim,

Pediatric health and respiratory diseases

Chronic obstructive pulmonary disease (COPD) is not familiar to the layperson nor even physicians in Korea. Instead, ‘haeso cheonsik’, which means ‘cough and dyspnoea’, is more familiar to Koreans and a relatively large proportion of the aged population suffers from haeso cheonsik. Haeso cheonsik could mean COPD, bronchial asthma or even heart failure, and therefore this frequent occurrence in the elderly, although not automatically meaning COPD, would suggest that a significant proportion of the elderly would have COPD. Chronic obstructive pulmonary disease is an important lung disease in Korea because Korea's population has a high rate of smoking and Korea became industrialized rapidly over the past 30 years. The rate of smoking is very high in Korea; 62.5% of men are smokers according to the 1999 report from Korean Tobacco and Ginseng Corporation. The rate of smoking increases sharply up to 72% of people aged in their 20s (when they graduate from high school and enter college), and then decreases slowly; but is always above 50% (Fig. 1). Percentage of men and women smoking in Korea. (Source: Korea Tobacco and Ginseng Corporation, 1999.) Because haeso cheonsik in the elderly is considered to be part of the ageing process, these patients frequently do not consult medical facilities. The occurrence of COPD, therefore, is underestimated in Korea. Also, because no epidemiological survey has been conducted in Korea there is no reliable data about the frequency of COPD in Korea. According to the information from the World Health Organization epidemiological data, the death rate from COPD for both sexes varies substantially between countries.1 The death rate from COPD in Japan is relatively low compared with Western countries. Korea and Japan are very close geographically and racially. Also, the Korean smoking population is similar to that of Japan (i.e. 62.5%vs 53%; Fig. 2). Percentage of men and women smoking in Asia. (Source: WHO, ACS, CDCDP.) The number of deaths from COPD as provided by Korea National Statistical Office has been available from 1983 and is published annually. The death rate in both sexes increased progressively from 1983 to 1999. The death rate more than doubled during this period, which is higher than the natural population growth (Fig. 3). Trend of COPD mortality in Korea (1983–1999). The importance of COPD is also suggested by a government report which stated that lower respiratory disorder is the tenth leading cause of death in Korean men. Lower respiratory disorders include bronchiectasis and tuberculosis sequelae and, therefore, does not automatically mean that COPD is the tenth leading cause of death. However, it does imply that COPD is an important disease in Korea. The economic burden of COPD on medical expenditure in Korea is not clear. Because dyspnoea is considered a normal ageing process, people with COPD frequently do not consult medical facilities until it is advanced. Also, when they are told that COPD cannot be cured by medication, a significant proportion of patients discontinue medical therapy. Even the Korean National Health Insurance Corporation does not have information on medical expenditure resulting from COPD because of inadequate software support. However, the cost of acute care for COPD is increasing because the number of admissions with COPD has increased steadily at Seoul National University Hospital during the last 10 years (Fig. 4). Number of admissions with chronic obstructive pulmonary disease in Seoul National University Hospital In conclusion, although COPD is not seen as frequently in Korea as it is in Western countries, it is steadily increasing and is becoming an important disease in the elderly people of Korea. The search for the susceptibility factor for COPD is being studied because only 10–15% of smokers develop chronic airway obstruction. Alpha-1 antitrypsin (α1AT) deficiency or abnormality is well known as a susceptibility factor in Western countries, but the importance of α1AT deficiency in Korea is not clear. Initial study of the relation between COPD and α1AT deficiency was conducted in 1980 by examining the serum level of α1AT in a normal population. To examine the normal level of α1AT in Korea, a total of 177 samples from the normal healthy population were examined by radial immunodiffusion. The range of α1AT was 258–489 mg/dL and no abnormal levels of α1AT were found (Table 1). Since 1980, COPD patients in the adult population and paediatric liver disease patients have been examined for the possibility of α1AT deficiency. Until now, no definite case of α1AT deficiency has been reported in Korea. At Seoul National University Hospital, about 90–100 samples are examined annually for α1AT by radial immunodiffusion. The normal range is 190– 350 mg/dL and even a patient with severe panlobular emphysema had normal serum levels. From October 1999 to October 2000, 93 samples were tested at Seoul National University Hospital. Among these, only one patient showed an abnormal result of 125 mg/dL. The patient was a 1-month-old baby who was admitted with acute gastroenteritis and milk allergy. There has been no evidence of liver disease to date. This patient could be the first patient with α1AT deficiency in Korea and further follow up examination is definitely needed (Table 2). For this workshop, I collected serum samples from 56 emphysema patients who visited Seoul National University Hospital. The subjects were all male and were above 50 years old. Their serum α1AT level, phenotype and genotype of α1AT gene were examined. The serum level of α1AT was measured in 56 patients by immunoassay using Boehring Nephelometers (Dade Boehring Marburg Gmbh, Germany). The normal range of Boehring Nephelometers was 90– 200 mg/dL. Patients data ranged from 99 to 212.6 mg/ dL (mean ± SD, 144.4 ± 26.5) (Table 3). No abnormality of serum α1AT level was found even though these patients had relatively severe emphysema. Phenotype of α1AT was examined in 36 patients by the isoelectric points of α1AT isoforms using PhastGel® DryIEF (Pharmacia, Sweden). No S or Z phenotype was found. Due to the lack of experience, subtype M is not clear at this stage (Fig. 5). Until the present study, there has been no report about the phenotypic abnormality of α1AT by isoelectric focusing in Korea. Phenotype analysis of alpha-1 antitrypsin. Genotype analysis was performed in 56 patients by multiplex polymerase chain reaction restriction fragment length polymorphism, according to the method reported by Rieger et al.2 and the result was compared with those of normal controls. No S or Z phenotype was found. The distribution of subtype M is similar between normal controls and emphysema patients. This result also showed that for M1 subtype, only M1 valine is found (Table 4). Even though this study is not a large scale study, it appears that α1AT Z or S gene is not an important cause of emphysema in Korea. However, there is still a possibility that another gene defect, such as the Siiyama variant which was found in Japan, could be a contributing factor in Korea. Further research is needed to find the prevalent type of genetic defect for emphysema through mass screening in Korea.