Abstract
Background: A multicenter study conducted in Southeast Asia to derive reference intervals (RIs) for 72 commonly measured analytes (general chemistry, inflammatory markers, hormones, etc.) featured centralized measurement to clearly detect regionality in test results. The results of 31 standardized analytes are reported, with the remaining analytes presented in the next report.
Method: The study included 63 clinical laboratories from South Korea, China, Vietnam, Malaysia, Indonesia, and seven areas in Japan. A total of 3541 healthy individuals aged 20–65 years (Japan 2082, others 1459) were recruited mostly from hospital workers using a well-defined common protocol. All serum specimens were transported to Tokyo at –80°C and collectively measured using reagents from four manufacturers. Three-level nested ANOVA was used to quantitate variation (SD) of test results due to region, sex, and age. A ratio of SD for a given factor over residual SD (representing net between-individual variations) (SDR) exceeding 0.3 was considered significant. Traceability of RIs was ensured by recalibration using value-assigned reference materials. RIs were derived parametrically.
Results: SDRs for sex and age were significant for 19 and 16 analytes, respectively. Regional difference was significant for 11 analytes, including high density lipoprotein (HDL)-cholesterol and inflammatory markers. However, when the data were limited to those from Japan, regionality was not observed in any of the analytes. Accordingly, RIs were derived with or without partition by sex and region.
Conclusions: RIs applicable to a wide area in Asia were established for the majority of analytes with traceability to reference measuring systems, whereas regional partitioning was required for RIs of the other analytes.
This research has been planned collaboratively by the: 1) C-PP and C-RIDL of the IFCC; 2) the Scientific Committee of the APFCB; 3) the Working Group on the Guideline for Common Reference Interval of the JSLM (Japan Society of Laboratory Medicine); and 4) the C-PP of the JSCC. This study was supported by the C-RIDL of the IFCC.
Research funds used included a Scientific Research Fund (No. 21406015: 2009-2011) provided by Japan Society for the Promotion of Science; a Research Promotion Project Fund of the JSLM (2008–2009); and a Scientific Research Fund of the APFCB.
Most of the reagents and labor required for testing such a large number of analytes were generously offered by BC. Additional reagents were provided by Nittobo Co. The sampling equipment (vacuum sample tubes, needles, and holders) were supplied by BD. Other expenses, such as serum container tubes, boxes, and ID labels, were purchased with the Scientific Research Funds offered by the APFCB.
The value-assigned specimens for the four steroid hormones were provided by L. Siekmann. A set of three fresh-frozen (−80°C) pooled sera for each of five enzymes (AST, ALT, LDH, GGT, and CK) were assigned values by the laboratories of F. Ceriotti and M. Panteghini based on the reference measurement procedures.
We are grateful to the participating laboratories and their staffs for their contributions to this study. The collaborating laboratories outside Japan were: 1) Gangnam Severance Hospital, Yonsei University, Seoul; 2) Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul; 3) Myongji Hospital, Kwandong University College of Medicine, Gyeonggi-do; 4) Peking University First Hospital, Beijing; 5) Mackay Memorial Hospital, Taipei; 6) Cathay General Hospital, Taipei; 7) Yuan Ching Clin Laboratory, Taipei; 8) National Cheng Kung University, Tainan; 9) Chi-Mei Medical Center, Tainan; 10) Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong; 11) Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau; 12) Medic-Lab, Ho Chi Minh City, 13) National Heart Institute, Kuala Lumpur; 14) Gleneagles Intan Medical Centre, Kuala Lumpur; and 15) Prodia Clinical Laboratory, Jakarta.
The collaborating laboratories within Japan included: 16) Keiyu Corp. Yoshida Hospital, Asahikawa; 17) Hokkaido University, Sapporo; 18) Kishimoto Clinical Laboratory, Tomakomai; 19) Iwate Medical School, Morioka; 20) Hirosaki University, Hirosaki; 21) Hachinohe Red-Cross Hospital, Hachinohe; 22) Hachinohe City Hospital, Hachinohe; 23) Chiba Cardiovascular Center, Ichihara; 24) Chiba University, Chiba; 25) Funabashi Municipal Medical Center, Funabashi; 26) Tokyo Medical and Dental University Chiba Hospital, Chiba; 27) Tokyo University, Tokyo; 28) Toho University, Tokyo; 29) Shinshu University, Matsumoto; 30) Matsumoto JAM Medical Center, Matsumoto; 31) Ohmachi Municipal Hospital, Omachi; 32) Yamanashi University, Kofu; 33) Fukui University, Fukui; 34) Kanazawa Medical School, Kanazawa; 35) SRL-Kanazawa, Kanazawa; 36) Mie University, Tsu; 37) Nagoya University, Nagoya; 38) Anjo Kosei Hospital, Anjo; 39) Fujita Health University, Toyoake; 40) Osaka University, Suita; 41) Tenri Hospital, Tenri; 42) Osaka Municipal University, Osaka; 43) National Cardiovascular Center, Suita; 44) Kawasaki Medical School, Kurashiki; 45) Kurashiki Central Hospital, Kurashiki; 46) Okayama University, Okayama; 47) Okayama Medical Laboratory, Kurashiki; 48) Matsuda Hospital, Kurashiki; 49) Hiroshima University, Hiroshima; 50) Yamaguchi University, Ube; 51) Tokuyama Central Hospital, Shunan; 52) Yamaguchi Prefectural Medical Center, Hofu; 53) Saiseikai Yamaguchi Hospital, Yamaguchi; 54) Saint Hill Hospital, Ube; 55) Kochi Medical School Hospital, Nangoku; 56) Kochi Red-Cross Hospital, Kochi; 57) Kochi National Hospital, Kochi; 58) Kumamoto University, Kumamoto; 59) CIS Hitoyoshi Laboratories, Hitoyoshi; 60) Tsuruta Memorial Clinic and Cancer Diagnostic Center, Miyazaki; 61) Eiwa Corp. Terada Hospital, Isa; 62) Ryukyu University, Naha; and 63) Adventist Medical Center, Naha.
This study is also indebted to Professor Giampaolo Merlini (University Hospital San Matteo), Professor Yoshihisa Itoh (Asahikawa Medical University), Emeritus Professor Takeshi Kanno (Hamamatsu University School of Medicine), Emeritus Professor Tadashi Kawai (Jichi University School of Medicine), Dr. Katsuhiko Kuwa (National Metrology Institute of Japan), Professor Susumu Osawa (Kyushu University School of Medicine), and Professor Shigemi Hosogaya (Kagawa Prefectural College of Health Sciences), who gave invaluable advice and encouragement to promote and carry out this study. Lastly, we are very grateful to Dr. Joseph Henny, Dr. Jose M. Queralto, and Dr. James C. Boyd as members of C-RIDL who gave us invaluable comments during a series of discussions on the scientific implications of this study.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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