Identification of non-invasive novel biomarkers predicting future asthma exacerbations in adults and early-onset wheeze in children

• Project/Area Number: 17K15843
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hygiene and public health
• Research Institution: Hokkaido University
• Principal Investigator: Goudarzi Houman 北海道大学, 医学研究院, 助教 (40713607)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: Birth cohort / childhood allergies / Overweight and obesity / Biomarkers / Early life wheeze / Urinary biomarkers / Allergies in children / Adult asthma cohort / Allergic diseases / Inflammatory biomarkers / Urine samples / Obesity / Asthma / birth cohort / adult asthma cohort

Outline of Final Research Achievements

We assessed association of early life allergic diseases with overweight/obesity risk in children at age 7. Also, we assessed the association of 3 urinary biomarkers including 8-hydroxy-2 deoxyguanosine (8-OHdG), hexanoyl-lysin (HEL), and 4-hydroxynonenal (4-HNE) with the risk of allergic diseases at age 7 (n=568) and 10 years (n=428). We found the prevalence of rhinitis (3.3 to 21.2%) and eczema (11.3% to 22.4%) increased from early life to age 10. Prevalence of wheeze peaked at 4 years of age (21.6%) with a decline at age 7 (13.3%) and 10 (9.2%). Among children aged 10, 41.5% had at least of the allergic diseases, 46.0% had FeNO >20 p.p.b, and 38.5% had blood eosinophil number >300/µl. At age 10, 70.5% and 22.3% of children were sensitized to inhaled and food allergens, respectively. Wheeze, but not other allergies, at age 0-2, 4 and 7 years of age was associated with risk of overweight/obesity at age 7. Also, HEL had higher levels among children with wheeze at age 7.

Academic Significance and Societal Importance of the Research Achievements

We found that early-life asthma may increase the risk of overweight/obesity. Thus, the prevention of overweight/obesity could be possible with early detection and treatment of asthma. We identified biomarkers associated with allergies and applicable as predictors of wheeze/asthma among children.

Research Products

• [Int'l Joint Research] University of Antwerp/Toxicological Center(ベルギー)
• [Int'l Joint Research] Center of Environmental Medicine/Kaohsiung Medical University, Taiwan/NIEHS(その他の国・地域)
• [Int'l Joint Research] Johns Hopkins University/School of Medicne(米国)
• [Int'l Joint Research] Toxicological Center/University of Antwerp/Belgium(ベルギー)
• [Int'l Joint Research] Taiwan/National Health Research Institutes/(NHRI)(その他の国・地域)
• [Journal Article] Combined exposure to phthalate esters and phosphate flame retardants and plasticizers and their associations with wheeze and allergy symptoms among school children (2020)
  • Author(s): Araki Atsuko、Ait Bamai Yu、Bastiaensen Michiel、Van den Eede Nele、Kawai Toshio、Tsuboi Tazuru、Miyashita Chihiro、Itoh Sachiko、Goudarzi Houman、Konno Satoshi、Covaci Adrian、Kishi Reiko
  • Journal Title: Environmental Research Volume: 183 Pages: 109212-109212
  • DOI: 10.1016/j.envres.2020.109212
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of Abdominal Visceral Adiposity on Adult Asthma Symptoms. (2019)
  • Author(s): Goudarzi H, Konno S, Kimura H, Makita H, Matsumoto M, Takei N, Kimura H, Shimizu K, Suzuki M, Ito YM, Nishimura M
  • Journal Title: The Journal of Allergy and Clinical Immunology: In Practice. Volume: 7 Issue: 4 Pages: 1222-1229
  • DOI: 10.1016/j.jaip.2018.11.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multiple exposures to organophosphate flame retardants alter urinary oxidative stress biomarkers among children: The Hokkaido Study (2019)
  • Author(s): Ait Bamai Yu、Bastiaensen Michiel、Araki Atsuko、Goudarzi Houman、Konno Satoshi、Ito Sachiko、Miyashita Chihiro、Yao Yiming、Covaci Adrian、Kishi Reiko
  • Journal Title: Environment International Volume: 131 Pages: 105003-105003
  • DOI: 10.1016/j.envint.2019.105003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Contrasting associations of maternal smoking and pre-pregnancy BMI with wheeze and eczema in children. (2018)
  • Author(s): Goudarzi H, Konno S, Kimura H, Araki A, Miyashita C, Itoh S, Ait Bamai Y, Kimura H, Shimizu K, Suzuki M, Ito YM, Nishimura M, Kishi R.
  • Journal Title: Science of the Total Environment Volume: 639 Pages: 1601-1609
  • DOI: 10.1016/j.scitotenv.2018.05.152
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Childhood allergies and obesity relationship: Identification of non-invasive biomarkers. (2019)
  • Author(s): 1.Houman Goudarzi, Satoshi Konno, Atsuko Araki, Sachiko Ito, Yu Ait Bamai, Chihiro Miyashita, Reiko Kishi.
  • Organizer: European Respiratory Society International Congress, Madrid, Spain
  • Int'l Joint Research
• [Presentation] Mixture Chemical Exposure in Utero and Boys Reproductive Hormone Levels at Birth: the Hokkaido study. (2019)
  • Author(s): 2.Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Takahiko Mitsui, Houman Goudarzi, Kazutoshi Cho, Kimihiko Moriya, Tamie Nakajima, Yusuke Iwasaki, Tsuguhide Hori, Junboku Kajiwara, Nobuo Shinohara, Reiko Kishi.
  • Organizer: Joint Meeting of Asian Chapters of International Society for Environmental Epidemiology and the International Society of Exposure Science (ISEE-ISES AC 2019), Daegu, Korea.
  • Int'l Joint Research
• [Presentation] Contrasting associations of maternal smoking and pre-pregnancy BMI with wheeze and eczema in children. (2019)
  • Author(s): 4.Goudarzi Houman、荒木敦子、伊藤 佐智子、アイツバマイゆふ、宮下ちひろ、木村孔一、今野 哲、岸 玲子.
  • Organizer: 第1回日本アレルギー学会北海道支部地方会.
• [Presentation] 学童の尿中リン酸トリエステル類代謝物濃度と尿中炎症関連マーカーとの関連 (Associations between urinary phosphorous frame retardant metabolites and urinary inflammation markers among school children). (2019)
  • Author(s): 5.アイツバマイ ゆふ、Bastiaensen Michiel、荒木 敦子、Goudarzi Houman 、今野哲、伊藤 佐智子、宮下 ちひろ、Covaci Adrian、岸 玲
  • Organizer: 第89回日本衛生学会学術総会. Nagoya, Japan.
  • Int'l Joint Research
• [Presentation] Differential impact of obesity indices on systemic and sputum inflammatory biomarkers among asthma patients. (2019)
  • Author(s): 7.Houman Goudarzi, Satoshi Konno, Hironi Makita, Hirokazu Kimura, Munehiro Matsumoto, Nozomu Takei, Hiroki Kimura, Kaoruko Shimizu, Masaru Suzuki, Masaharu Nishimura.
  • Organizer: The 59th Annual Meeting of the Japanese Respiratory Society, Tokyo, Japan.
  • Int'l Joint Research
• [Presentation] Differential impact of obesity indices on systemic inflammatory biomarkers among asthma patients (2019)
  • Author(s): Houman Goudarzi, Satoshi Konno, Hironi Makita, Hirokazu Kimura, Munehiro Matsumoto, Nozomu Takei, Hiroki Kimura, Kaoruko Shimizu, Masaru Suzuki, Masaharu Nishimura
  • Organizer: The 58th Annual Meeting of the Japanese Respiratory Society, 2019 April 12-14, Tokyo, Japan
  • Int'l Joint Research
• [Presentation] 学童の尿中リン酸トリエステル類代謝物濃度と尿中炎症関連マーカーとの関連 (2019)
  • Author(s): アイツバマイ ゆふ、Bastiaensen Michiel、荒木 敦子、Goudarzi Houman 、今野哲、伊藤 佐智子、宮下 ちひろ、Covaci Adria、岸 玲.
  • Organizer: 衛生学会学術総会. 2019 February 1-3, Nagoya, Japan.
  • Int'l Joint Research
• [Presentation] Distinct impact of abdominal visceral adiposity on asthma symptoms. (2018)
  • Author(s): Goudarzi H, Konno S, Kimura H, Makita H, Matsumoto M, Takei N, Kimura H, Shimizu K, Suzuki M, Nishimura M.
  • Organizer: European Respiratory Society International Congress, 2018 September 15-19, Paris, France.
  • Int'l Joint Research
• [Presentation] Contrasting associations of maternal smoking and BMI with wheeze and eczema in children. (2018)
  • Author(s): Goudarzi H, Konno S, Kimura H, Araki A, Miyashita C, Itoh S, Ait Bamai Y, Kimura H, Shimizu K, Suzuki M, Ito YM, Nishimura M, Kishi R.
  • Organizer: Japanese Society of Allergology (JSA) 67th Annual Meeting 2018 June 22-24, Chiba, Japan.
  • Int'l Joint Research
• [Presentation] Distinct impact of abdominal visceral adiposity on asthma symptoms. (2018)
  • Author(s): Goudarzi H, Konno S, Kimura H, Makita H, Matsumoto M, Takei N, Kimura H, Shimizu K, Suzuki M, Nishimura M.
  • Organizer: The 58th Annual Meeting of the Japanese Respiratory Society, 2018 April 27-29, Osaka, Japan.
  • Int'l Joint Research
• [Remarks] The Best Presentation Award in 2018
  • URL: http://fdm.med.hokudai.ac.jp/trainee/iryou/special/2017/special04-2.html
• [Remarks] Outstanding Reviewer Award in 2018
• [Funded Workshop] Scientific writing workshop (2019)
• [Funded Workshop] Human biomonitoring of emergent contaminants (workshop) (2019)