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Birth cohort study on the effects of desert dust exposure on children's health: protocol of an adjunct study of the Japan Environment & Children’s Study

Introduction Desert dust is estimated to constitute about 35% of aerosol in the troposphere. Desertification, climatic variability and global warming all can contribute to increased dust formation. This study aims to examine possible health effects of desert dust exposure on pregnant women and their children. The purpose of this report was to present the study protocol. Methods and analysis This 4-year birth cohort study began in 2011 as an adjunct study of the Japan Environment & Children’s Study (JECS) involving three regions: Kyoto, Toyama and Tottori. The JECS participants of the three regions above who also agreed to participate in this adjunct study were enrolled prior to delivery. Light Detecting and Ranging (LIDAR) with a polarisation analyser, which can distinguish mineral dust particles from other particles, is used for exposure measurements. Outcomes are allergic symptoms for mothers and development of asthma and other allergic or respiratory diseases for their children. Data are acquired in a timely manner by connecting local LIDAR equipment to an online questionnaire system. Participants answer the online questionnaire using mobile phones or personal computers. Ethics and dissemination The study protocol was approved by the ethics committees of Kyoto University, University of Toyama and Tottori University. All participants provided written informed consent. The results of this study will be published in peer-reviewed journals and disseminated to the scientific community and general public. Trial Registration number UMIN000010826.

This cohort study collects data on environmental exposure during the period from pregnancy to early infancy and potential confounding sources as well. A comprehensive analysis of this information will allow us to explore the role of desert dust exposure on allergic/respiratory diseases.
Participants' mobile phones or personal computers are used for their access to web-questionnaires, and therefore those who do not use mobile phones or personal computers are not inquired, and the response inconsistency across different media is also a weakness our study, because participants' devices are not uniform. years 2 . Desert dust particles are principally composed of rock-forming minerals such as quartz, and clay minerals such as mica and kaolinite. Additional particle analysis also showed the presence of microbial agents such as bacteria, fungi, fungal spores and viruses 3,4,5,6 , as well as anthropogenic atmospheric pollutants likely absorbed during transport 7 . Recent evidence reveals several possible negative effects of these dust particles on human health. Administration of desert dust sand to murine bronchi exerted adjuvant effects in the airway 8,9 , and inhalation of desert dust in patients with mild asthma caused a significant decrease in forced expiratory volume 10 . Epidemiological studies showed that desert dust events were associated with health outcomes such as exacerbated asthma in Spain, the Caribbean, Japan, Korea, China, Taiwan and other locations [11][12][13][14][15][16][17][18][19][20] . Although there have been many reports on urban pollution that examined both the direct association and vulnerable populations, as well as possible countermeasures and their effectiveness 21,22 , only a few have quantified direct associations between desert dust and human

Objectives
The study has the following objectives: (i) examine possible effects of desert dust exposure to health outcomes such as the development of allergies or asthma for infants, outgrowing asthma for asthma infants, and worsening of respiratory and allergic symptoms for pregnant women; (ii) perform further analysis for potential associations, including the degree to which the effect is lessened by avoidance behaviors, identification of groups vulnerable to dust exposure and effect modifiers, exploration of possible local differences in effects of desert dust exposure and what in the dust exerts the effects; (iii) analysis for further understanding the benefits and limitations of a web-based questionnaire by comparing demographic Outcome: For outcome measurement of day-to-day symptoms, a self-administered questionnaire including items from a Japanese version of the Allergy Control Score TM 38 is issued to participants via mobile phones and/or personal computers. For outcome measurement of allergic disease incidence of infants, a self-administered questionnaire is sent to mothers via mobile phone every six months after childbirth. The questionnaire includes The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire 39 , lifetime wheezing/whistling and wheezing/whistling during the past six months, sleep disturbance due to wheezing, and physicians' diagnoses of asthma and other allergic diseases.
Details of measurement items are presented in Table 1. The study used a web-based survey that provides the benefits of an automatic validation check, automatic reminder and automatic random selection of questions. Subject selection, however, is generally considered a significant weak point of web-based studies, particularly those that also recruit participants online 30 . Our study tried to resolve this issue by recruiting participants through an ongoing cohort study that targets a relatively young population, where nearly universal Internet access is achieved (99%). Other concerns associated with web-based surveys include lack of participant access to computers with Internet connections, Internet privacy concerns and response inconsistency across different media. We tried to overcome these potential problems by using participants' individual mobile phones and/or personal computers, a secure server equipped with a firewall and password protection and uploading no personal data other than the e-mail address on the server. Response inconsistency across different media was a weakness our study may not have been able to overcome because participants' devices were not uniform.
Other than this limitation, generalizability of the result may become a concern, because this additional study follows about one-quarter of the newborns in the study area, those who do not use mobile phones or personal computers were not enrolled, and some attrition occurred mainly due to individuals moving outside the study area. However, background of the participants as of the end of 2012 was overall similar with that reported in Japanese government statistics 40-43 (data not shown) and the attrition were relatively     Web-based questionnaire for assessing the child's exposure level is issued on the day the dust is observed (brown) and on some randomly selected days (green).

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For peer review only -http://bmjopen.bmj.com/site/about/guidelines.xhtml 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  Adjunct study protocol after birth Web-based questionnaire for assessing the child's exposure level is issued on the day the dust is observed (brown) and on some randomly selected days (green). Web-based questionnaire for the child's outcome is sent every 6 months after the child is born until the child becomes 4 years of age.    In this cohort study, data on environmental exposure during the period from pregnancy to early infancy, as 59 well as potential confounding sources, are collected. A comprehensive analysis of this information will 60 allow us to explore the role of desert dust exposure on allergic/respiratory diseases.

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Our birth cohort examines possible effects of desert dust exposure to health outcomes, using 110 web-based questionnaires connected to an environment measurement system, allowing for the collection of 111 information within a short time frame. This report aims to inform the relevant research community of our 112 study objectives, design, and progress.

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'Effects of desert dust exposure on children's health' is our adjunct study involving three JECS Regional

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of asthma or other allergic diseases is compared between those exposed to high or low levels of desert dust.

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The intent of this cohort study is to collect data on environmental exposure during the period from 256 pregnancy to early infancy and to control for potential confounding sources.          467 Figure 4. Adjunct study protocol after birth

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A web-based questionnaire for assessing the child's exposure level is issued on the day dust is observed

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(brown) and on some randomly selected days (green).

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A web-based questionnaire for assessing child outcomes is sent every 6 months after the child is born until 471 the child reaches four years of age.

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Our birth cohort examines possible effects of desert dust exposure to health outcomes, using 110 web-based questionnaires connected to an environment measurement system, allowing for the collection of 111 information within a short time frame. This report aims to inform the relevant research community of our 112 study objectives, design, and progress.

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This study has the following objectives: (i) examine possible effects of desert dust exposure on 115 health outcomes such as the development of allergies or asthma for infants (long-term effects), and 116  paper-based answers. The primary hypothesis is that the development of asthma at the age of four in those 124 exposed to high level of desert dust is more than 1.5 times greater than those exposed to low level of desert

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Toyama, or Tottori regional centres were informed of this adjunct study. Those who agreed to participate 167  of asthma or other allergic diseases is compared between those exposed to high or low levels of desert dust.

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Time to development of asthma or other allergic diseases between the two groups is also examined.  the 5% significance level between children exposed to high and low levels of desert dust, assuming the 186 incidence of asthma in those with low exposure is 1.5%. We also evaluated the sample size needed for our 187 secondary objective, which is to assess the association between desert dust exposure and allergic symptom 188 worsening in pregnant women, and confirmed that the sample size used for the primary objective is   Table 1 and the questionnaire is shown in Appendix.    The primary analysis compares the development of asthma at the age of four between highly exposed and 218 lowly exposed (lower than the 1st quantile and higher than the 4th quantile of the cumulative value of 219 day-average dust levels from birth, respectively) infants. Time to development of asthma or other allergic 220 diseases between the two groups is also examined. For short-term effects on pregnant mothers, we will 221 compare the proportion of those with any symptom (symptom score above 0) between Asian dust days 222 (dust level ≥0.07/km ) and control days (dust level <0.07/km) for the primary analysis, and will also 223 conduct sensitivity analysis including a comparison of the log score between these days. The generalized 224 estimating equation (GEE) is used to adjust inter-individual correlations, as appropriate.

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The following factors will be examined for possible confounders and possible effect modifiers:

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lowest temperature, humidity). Data will be analysed as follows: (1) Each factor will be examined for the 236 association with the outcomes using threshold models with various cut-off values, and the best model will

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The intent of this cohort study is to collect data on environmental exposure during the period from 256 pregnancy to early infancy and to control for potential confounding sources.

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(brown) and on some randomly selected days (green).

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A web-based questionnaire for assessing child outcomes is sent every 6 months after the child is born until 465 the child reaches four years of age.  Over the course of the week, how often were you exposed to sunlight for more 565 than 15 minutes during the period from 9 am to 3 pm? Please include the time 566 spent exposed to sunlight under trees or under light clouds. 567 * Choose 'already answered' if you already answered this question within a week. 568 * Count only instances in which the exposed skin surface was equivalent to an 569 area of more than two adult palms. 570 Adjunct study protocol after birth Web-based questionnaire for assessing the child's exposure level is issued on the day the dust is observed (brown) and on some randomly selected days (green). Web-based questionnaire for the child's outcome is sent every 6 months after the child is born until the child becomes 4 years of age. 90x41mm (300 x 300 DPI)  On a typical day, how often are you exposed to sunlight for more than 15 minutes 19 from 9 am to 3 pm? Please include the time spent exposed to sunlight under 20 trees or under light clouds. 21 ◎ More than 5 days a week 23 ◎ 3-4 days a week 24 ◎ 1-2 days a week 25 ◎ rarely 26 27 How often, for leisure purposes only, are you exposed to sunlight for more than 28 15 minutes from 9 am to 3 pm? Please include the time spent exposed to sunlight 29 under trees or under light clouds. 30 ◎ almost weekly 31 ◎ 2-3 times a month 32 ◎ once a month 33 ◎ rarely 34 Over the course of the week, how often were you exposed to sunlight for more 96 than 15 minutes during the period from 9 am to 3 pm? Please include the time 97 spent exposed to sunlight under trees or under light clouds. 98 * Choose 'already answered' if you already answered this question within a week. 99 * Count only instances in which the exposed skin surface was equivalent to an 100 area of more than two adult palms. 101

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In this cohort study, data on environmental exposure during the period from pregnancy to early infancy, as 55 well as potential confounding sources, are collected. A comprehensive analysis of this information will 56 allow us to explore the role of desert dust exposure on allergic/respiratory diseases.

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Our birth cohort examines possible effects of desert dust exposure to health outcomes, using 106 web-based questionnaires connected to an environment measurement system, allowing for the collection of 107 information within a short time frame. This report aims to inform the relevant research community of our 108 study objectives, design, and progress.

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This study has the following objectives: (i) long-term effects; examine possible effects of desert 111 dust exposure on the development of allergies or asthma in infants, (ii) short-term effects; worsening of 112  paper-based answers. The primary hypothesis is that the development of asthma at the age of four in those 120 exposed to high level of desert dust is more than 1.5 times greater than those exposed to low level of desert

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'Effects of desert dust exposure on children's health' is our adjunct study involving three JECS Regional

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Toyama, or Tottori regional centres were informed of this adjunct study. Those who agreed to participate 163  of asthma or other allergic diseases is compared between those exposed to high or low levels of desert dust.

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The intent of this cohort study is to collect data on environmental exposure during the period from 256 pregnancy to early infancy and to control for potential confounding sources. Our task of collecting 257 individual data on behaviour related to dust exposure on the same day by sending an automatic e-mail to 258 participants based on LIDAR system measurements was successful, as demonstrated by the high response 259 rate of 88% as of the end of 2012. To our knowledge, this is the first study that connects an environmental 260 measurement system to a questionnaire system, thereby reducing the burden on participants by providing 261 the questionnaire only at necessary times.

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A web-based questionnaire for assessing the child's exposure level is issued on the day dust is observed

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(brown) and on some randomly selected days (green).

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'Effects of desert dust exposure on children's health' is our adjunct study involving three JECS Regional

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Toyama, or Tottori regional centres were informed of this adjunct study. Those who agreed to participate 164  of asthma or other allergic diseases is compared between those exposed to high or low levels of desert dust.

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Time to development of asthma or other allergic diseases between the two groups is also examined. the 5% significance level between children exposed to high and low levels of desert dust, assuming the 183 incidence of asthma in those with low exposure is 1.5%. We also evaluated the sample size needed for our 184 secondary objective, which is to assess the association between desert dust exposure and allergic symptom 185 worsening in pregnant women, and confirmed that the sample size used for the primary objective is  Table 1 and the questionnaire is shown in Appendix.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59

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A web-based questionnaire for assessing the child's exposure level is issued on the day dust is observed

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(brown) and on some randomly selected days (green).