2018 Fiscal Year Research-status Report
Identification of non-invasive novel biomarkers predicting future asthma exacerbations in adults and early-onset wheeze in children
| Project/Area Number |
17K15843
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Keywords | Allergic diseases / Adult asthma cohort / Birth cohort / Inflammatory biomarkers / Urine samples / Obesity |
|---|
| Outline of Annual Research Achievements |
The parallel epidemics of asthma and obesity, over the past few decades, have spurred research into obesity and asthma relationship. Therefore, we examined the bidirectional association of asthma and obesity along with urinary biomarkers in children and adults:
1)Hokkaido birth cohort: We assessed the effects of allergies on BMI at age 7 (n=5,158). Parents completed the International Study of Asthma and Allergies in Childhood questionnaires about wheeze, rhinitis, and eczema at age 1, 2, 4, and 7 years. BMI (kg/m2) was measured at age 7. We also examined three inflammatory urine biomarkers at age 7 including 8-OHdG, hexanoyl-lysin (HEL), and 4-Hydroxynonenal (HNE) (n = 568). Wheeze at age 1, 2, and 4 years of age was significantly associated with higher BMI at age 7. In contrast, rhinitis and eczema did not show significant association with BMI at age 7. HEL, as one of omega 6 fatty acid oxidation biomarkers, had higher urinary levels in children with wheeze at age 7. Other urinary biomarkers did not show any association with BMI and other allergic diseases at age 7. Also, we found that prenatal maternal BMI is associated with a higher risk of wheeze at age 7 independent of childhood BMI.
2)Adult asthma cohort: We examined urinary HEL and HNE (n= 210). We stratified patients by BMI (less or more than 25 kg/m2) and asthma severity (severe vs. non-severe) into four groups. HEL levels were the highest among overweight/obese severe asthma patients compared to the other groups. Also, we found a significant positive association of abdominal visceral adiposity and urinary HEL.
|
| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Primarily, we did an extensive literature review to find novel and promising biomarkers in urine in adults and children, predicting inflammatory condition and future adverse events such as the development of allergies, asthma exacerbation, and obesity. We determine to focus on HEL and HNE according to collaboration with some colleagues in Taiwan and the USA. First, we planned to measured lipid peroxidation biomarkers in urine samples of adult asthma cohort (n=210). We could measure HEL and HNE with 100 and 90% detection rate, respectively. Coefficient of variation (CV) was less than 10% for measurement which indicates the high quality of biomarker measurements in our study. Therefore, we could establish a reliable protocol for measurement of HEL and HNE with ELISA. We applied the same protocol for measurement of urinary biomarkers in children and we could measure them with 100% detection rate and low CV (n=568). Because of very smooth teamwork between Department of Respiratory Medicine and Center for Environmental and Health Sciences in Graduate School of Medicine, Hokkaido University, working on two prospective ongoing cohorts (birth and adult cohorts) with enough sample size, we could get significant progress smoothly. With an interdisciplinary research approach, we could get progress smoothly for biomarker measures, obesity and allergic diseases assessment using our previous experiences, optimizing the measurement protocols targeting promising biomarkers, in addition to using standard questionnaires, and clinical outcome assessment.
|
| Strategy for Future Research Activity |
1)Hokkaido birth cohort: We have assessed and published association of maternal and childhood obesity with risk of childhood allergic diseases using my grant (Goudarzi et al. STOTEN, 2018). Additionally, we examined the role of allergic diseases as one of the risk factors of childhood obesity. Furthermore, we developed urinary biomarkers with non-invasive methods for allergic diseases and obesity which is easy to detect in a routine clinical setting. It may provide practically applicable biomarkers for the inflammatory condition in allergies, asthma and obesity to predict disease development and activity in children and adults. This could eventually lead to predict and prevent the development of allergies and obesity, better monitoring/management of these diseases, and reduction of the economic burden of chronic diseases. Now, I am preparing two manuscripts about i) bidirectional association of childhood allergies and obesity; and ii) mechanistic association of urinary biomarkers with allergies and obesity. These results have been presented in several International conferences by me and colleagues.
2)Adult asthma cohort: Recently, I published a paper regarding the association of obesity indices (especially abdominal visceral adiposity) with poor asthma symptoms in a very prestigious journal which is the second top allergy journal in the world (Goudarzi et al. JACI: In Practice, 2019). As next plan, I examine effect of urinary biomarkers on the risk of asthma exacerbation in adults with a prospective approach. I have presented the results in three international conferences.
|
| Causes of Carryover |
Recently, we have finished the measurement of urinary biomarkers in both children and adults with significant sample size. We need more time to finish data analysis in both cohorts, compare our findings in children vs. adults, to share the findings with scientists in domestic and international conferences and prepare high-quality manuscripts to publish in international journals. Therefore, we needed more time to complete the project in the best shape and highest quality and outcome. We are also planning to share the findings with participants of our cohorts and Japanese citizens with simple language and we believe that dissemination of this scientific information would promote healthier society among children and adults.
|
| Remarks |
1) The Best Presentation Award in 66th Annual Meeting of Japanese Society of Allergology, 2017, Tokyo, Japan
2) I received Outstanding Reviewer Award for Environment International (ELSEVIER)in 2018
|
