Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches: Assessment of Health Outcomes in Children With Asthma and in Adults With Atrial Fibrillation During Desert Dust Storms (With vs Without Interventions)
Phase: NA
Conditions: Asthma in Children, Atrial Fibrillation
Sponsor: University of Cyprus

Life+ MEDEA Action C7 Protocol, Version 1.0 
                                
April 2018 
Mitigating the Health Effects of Desert Dust 
Storms Using Exposure-Reduction 
Approaches    
(MEDEA) project 
 
 
ACTION C.7: Assessment of health outcomes 
in children with asthma during desert dust 
storm (DDS) events (with vs without 
intervention measures) 
 
Public Health Interventional Study 
Protocol Template 
(April 2018) 
 
 

Life+ MEDEA Action C7 Protocol, Version 1.0 
                                
April 2018 
MITIGATING THE HEALTH EFFECTS OF DESERT DUST STORMS 
USING EXPOSURE-REDUCTION APPROACHES    
(MEDEA) PROJECT 
 
 
ACTION C.7: ASSESSMENT OF HEALTH OUTCOMES IN CHILDREN 
WITH ASTHMA DURING DESERT DUST STORM (DDS) EVENTS 
(WITH VS WITHOUT INTERVENTION MEASURES) 
Principal Investigator and Action Leader: 
 
Name: Dr. Panayiotis Yiallouros 
Position: Professor of Paediatrics 
Department: Medical School 
University: University of Cyprus  
Supported by: 
LIFE+ 2016 
The MEDEA project is funded by the European LIFE+ 2016 Climate Change Adaptation 
programme 
 (LIFE16 CCA/CY/000041) 
 Version 1  
April, 2018

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TABLE OF CONTENTS 
Page 
TABLE OF CONTENTS ............................................................................................................. 2 
STUDY TEAM ROSTER............................................................................................................. 4 
Local Study Coordinator: Dr. Panayiotis Yiallouros ............................................................... 4 
Summary ........................................................................................................................................ 5 
Study Title ................................................................................................................................... 5 
Objectives ................................................................................................................................... 5 
Design, Interventions and Outcomes .......................................................................................... 5 
Duration ...................................................................................................................................... 6 
Study Population ......................................................................................................................... 7 
1 
STUDY OBJECTIVES ......................................................................................................... 8 
1.1 
Primary Objective ........................................................................................................... 8 
1.2 
Secondary Objectives...................................................................................................... 8 
2 
BACKGROUND AND RATIONALE ................................................................................ 8 
2.1 
Background on Condition, Disease, or Other Primary Study Focus .............................. 8 
2.2 
Study Rationale ............................................................................................................... 9 
3 
STUDY DESIGN ................................................................................................................. 10 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS .......................................... 11 
4.1 
Inclusion Criteria .......................................................................................................... 11 
4.2 
Exclusion Criteria ......................................................................................................... 12 
4.3 
Study Enrollment Procedures ....................................................................................... 12 
5 
STUDY INTERVENTIONS .............................................................................................. 12 
5.1 
Interventions, Administration, and Duration ................................................................ 12 
5.2 
Handling of Study Interventions ................................................................................... 14 
5.3 
Adherence Assessment ................................................................................................. 15 
6 
STUDY PROCEDURES .................................................................................................... 16 
6.1 
Schedule of Evaluations ................................................................................................ 16 

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6.2 
Description of Evaluations ............................................................................................ 17 
6.2.1 Screening and Enrollment Evaluation ...................................................................... 17 
6.2.2 Baseline, and/or Randomization ............................................................................... 17 
6.2.3 Follow-up Assessments ............................................................................................ 18 
6.2.4 Completion/Final Evaluation .................................................................................... 19 
7 
ASSESSMENTS OF ADVERSE EVENTS ...................................................................... 19 
8 
INTERVENTION DISCONTINUATION........................................................................ 19 
9 
DATA COLLECTION ....................................................................................................... 20 
9.1 
Data Collection Forms .................................................................................................. 20 
9.2 
Data Management ......................................................................................................... 20 
10 PARTICIPANT RIGHTS AND CONFIDENTIALITY ................................................. 21 
10.1 
Informed Consent Forms .............................................................................................. 21 
10.2 
Participant Confidentiality ............................................................................................ 21 
11 ETHICAL CONSIDERATIONS ....................................................................................... 22 
12 COMMITTEES................................................................................................................... 23 
13 REFERENCES .................................................................................................................... 23 
14 SUPPLEMENTS/APPENDICES ...................................................................................... 24 
I. Informed Consent Form Templates 
  
 
 

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STUDY TEAM ROSTER  
   
 
Cyprus 
Local Study Coordinator: Dr. Panayiotis Yiallouros 
Address: Medical School 
University of Cyprus 
215/6 Palaios dromos, Nicosia-Limassol 
2029 Aglantzia 
Nicosia, Cyprus 
Telephone: 22895212 
Fax: 22895396 
e-mail address: yiallouros.panayiotis@ucy.ac.cy  
 
Cyprus team members: 
Panayiotis Kouis, PhD 
Maria Kakkoura, PhD 
Paraskevi Kinni 
Margarita Kaliva 
 
 
Greece 
 
Local Study Coordinator: Dr. Emmanouel Galanakis 
 
  
Address: School of Medicine,  
University of Crete, 
Voutes Campus, 
Heraklion, Crete, 
GR-71003, Greece 
 
Greece team members 
Dr Eleni Michailidi 
Dr Chrysoula Perdikogianni 
Dr Lena Dimitriou 
Julieta Pérez 
 
 

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SUMMARY 
Study Title  
Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches 
(LIFE+ MEDEA) 
Objectives  
The primary objective of this panel study will be to quantify the vulnerability of children with 
asthma during desert dust storm (DDS) outbreaks and provide evidence-based estimates 
demonstrating which interventions/recommendations work best in mitigating adverse health 
effects in this group of patients (primary outcome: difference of 3 points in the Asthma Control 
Test (ACT) questionnaire score) after randomization to three parallel intervention groups:  
a) No intervention for DDS 
b) Intervention for outdoor exposure reduction, and  
c) Interventions for both outdoor and indoor exposure reduction 
 
The secondary objectives of the study are to: 
1. Demonstrate which of the recommendations are effective in reducing outdoor and indoor 
exposures to DDS in a panel of children with asthma. 
2. Assess secondary health outcomes, such as the presence or absence of asthma symptoms 
in the prior 4 week period and unscheduled visits for asthma. 
 
Design, Interventions and Outcomes   
Type of study: Public Health Intervention Study  
 
Intervention: Children with asthma will be recruited and will be randomized during the high DDS 
outbreaks season (Spring 2019 and 2020) with 1:1:1 ratio into three parallel groups to receive: 
a) No intervention for DDS. 
b) Intervention for outdoor exposure reduction, by reducing the time spend outdoors and by 
avoiding physical activity. 
c) Interventions for outdoor (as above) and indoor exposure reduction (by minimizing home 
ventilation and filtering indoor air). 
 
Disease-related adverse health outcomes will be assessed in the three parallel arms of the study.  
 
Approaches for delivering the intervention:  
 A bidirectional, patient-centered e-Platform will be developed in order to facilitate prompt 
communication with the participants and provide early warnings regarding forecasted 
upcoming DDS events through text messaging and smartphone applications. Furthermore, 
the same IT platform and mobile application will be utilised for the dissemination of the 

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exposure reduction guidelines that the participants will follow. 
 
Assessment of adherence to intervention:  
 Monitor compliance to exposure-reduction guidelines using remote sensors. The 
intervention for outdoor exposure reduction, entailing reduction of the time spend 
outdoors and avoidance of physical activity, will be assessed with the use of smart 
wristwatches that will be equipped with Global Positioning System (GPS) and an 
accelerometer. 
 The intervention for indoor exposure reduction, entailing minimization of home 
ventilation and filtering of indoor air, will be assessed with the use of particle samplers 
that will be placed outside and inside of houses and school classrooms. 
 
Assessment of health outcomes: 
 Phone interviews at baseline and then at every 1 month throughout the high DDS period 
recording information on asthma medication use and unscheduled visits to health 
professional for asthma.  
 Frequency of respiratory symptoms will be assessed via caregiver and child’s responses to 
questions on daytime and night-time symptoms in the past 4 weeks, with the help of a 
validated Greek version of the ACT. 
 Specific aeroallergen sensitivities will be assessed at baseline and Lung function, FeNO at 
baseline, middle and end of high DDS season. 
 
Primary health outcome will be a change of 3 points in the ACT questionnaire score. For the 
primary analysis we will compare the combined effect in the two intervention groups versus the 
control group. Next, we will compare between each of the intervention groups and control group 
and between the intervention groups. 
Secondary health outcomes will be the presence or absence of asthma symptoms in the prior 4-
week period, asthma medication use, unscheduled visits for asthma, forced expiratory volume in 
1 second, peak expiratory flow, and FeNO. 
Duration  
Duration of the study: A feasibility (pilot) trial aiming to the refinement of protocols and tools will 
be performed during the high DDS outbreaks season of 2018. During the fall 2018 and 2019, with 
the onset of academic year, screening survey questionnaires (International Study of Asthma and 
Allergies in Children, ISAAC) will be addressed to the parents of all children in 18-20 primary 
schools in Nicosia by the MEDEA personnel to detect and enrol eligible asthmatic children 
(recruitment procedure) for the two main study periods (high DDS outbreaks season of February 
to May 2019 and 2020). Data collection, data cleaning and statistical analysis will take place in 
2020. 

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Study Population  
Study population, sample size and location: Children with mild to moderate persistent asthma, 
aged 6-11 years, will be recruited from primary schools in Nicosia-Cyprus (n=150) in academic 
years 2018-2019 and 2019-2020. In order to facilitate recruitment, schools principals will be 
contacted individually at the beginning of each academic year and details of the study will be 
explained. Relations with the Administrative and Nursing staff of the Schools and Parents 
Associations will be established with the aim to facilitate field work. During fall 2018 and 2019, 
MEDEA personnel will start recruitment efforts to detect eligible children with asthma for 
participation in the study in the high DDS periods of February-May 2019 and 2020. The same 
number of children will be recruited at the second study site of Heraklion-Crete.  
With an average number of 250 students per school, a childhood asthma prevalence of 9-10% and 
an estimated response of 60%, in 18-20 primary schools we expect to detect 300 students with 
reported asthma. We expect that 50% of the children with reported asthma will meet eligibility 
criteria giving us for randomization 150 subjects in Nicosia. We estimate a dropout rate of 30%, 
which will eventually give us 105 asthmatic children in total to analyze. 
The feasibility of protocols to assess health outcomes with and without implementation of 
exposure reduction guidelines will be tested in a pilot study during the high DDS period of 2018 
at both study sites in a small number of patients (6 children with asthma per study site). 
 
 
 
 
 

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1 
STUDY OBJECTIVES 
1.1 Primary Objective 
 
The primary objective of this panel study will be to quantify the vulnerability of children with 
asthma during DDS outbreaks and provide evidence-based estimates demonstrating which 
interventions/recommendations work best in mitigating adverse health effects in this group of 
patients after randomization to three parallel intervention groups:  
a) No intervention for DDS 
b) Intervention for outdoor exposure reduction, and  
c) Interventions for both outdoor and indoor exposure reduction 
 
The primary health outcome will be a change of 3 points in the Asthma Control Test (ACT) 
questionnaire score. For the primary analysis we will compare the combined effect in the two 
intervention groups versus the control group. Next, we will compare between each of the 
intervention groups and control group and between the intervention groups. 
 
1.2 Secondary Objectives 
 
The secondary objectives of the study are to: 
1. Demonstrate which of the recommendations are effective in reducing outdoor and indoor 
exposures to DD in a panel of asthmatic children. 
2. Assess secondary health outcomes including the presence or absence of asthma symptoms 
in the prior 4-week period, asthma medication use, unscheduled visits for asthma, forced 
expiratory volume in 1 second, peak expiratory flow, and FeNO. 
 
 
2 
BACKGROUND AND RATIONALE  
2.1 Background on Condition, Disease, or Other Primary Study Focus 
 
The MEDEA project is envisioned to provide the field-based evidence for the adoption of a 
strategic plan for mitigating the health effects of DDS events in South-Eastern Europe. Over 
the past decade, several studies have demonstrated that DDS in Mediterranean countries, 
originating mostly from the Sahara and Arabian Peninsula deserts, have been increasing in 
number and magnitude and linked it to desertification, climatic variability and global 
warming. EU legislation considers DDS impossible to prevent, implicitly harmless and 
discounts their contribution to daily and annual air quality standards of particulate matter up 
to 10 microns (PM10). 

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However, there is increasing evidence from epidemiological studies which correlates 
exposure to PM10 during DDS with a significant increase in mortality and hospital 
admissions from cardiovascular and respiratory causes. Therefore, there is a pressing need 
for EU policies to reduce population exposures and increase individual, population and 
institutional resilience to the growing frequency and intensity of DDS. 
MEDEA ultimate goal is to demonstrate the feasibility and effectiveness of an adaptation 
strategy to DDS and better inform EU policy making. 
 
2.2 Study Rationale 
 Desert dust storm events across Southern Europe 
A dust storm is a phenomenon common to arid and semi-arid regions. In the EU, the term 
“Desert Dust Storms (DDS)” is used in the context of sandstorms originating primarily from 
the Sahara desert but also from the Arabian–Negev desert. The term DDS refers to the 
condition created when finer sand particulate matter (PM) from the desert surface is 
transported over a long distance. DDS pose a major risk to populations residing in affected 
areas, such as in Mediterranean countries belonging to the global dust belt, extending from 
West Africa to the Arabian Peninsula (Querol et al., 2009). During DDS events, which can 
last for several days, PM10 levels are considerably higher than the 2005 EU daily limit value 
of 50 μg/m3 (Achilleos et al, 2014). Dust PM is mostly composed of rock-forming and clay 
minerals and they may carry microbial agents, such as bacteria, fungi and viruses (Griffin et 
al, 2007), and mix with anthropogenic atmospheric pollutants during transport. 
 
Associations of DDS with mortality and hospital admissions 
Historically, DDS were not considered harmful to humans due to their natural origin and 
crustal composition; however, in recent years, a large number of studies worldwide and in 
particular from Cyprus (Middleton et al., 2008; Neophytou et al., 2013), Greece (Samoli et 
al., 2011), Italy (Mallone et al., 2011) and Israel (Vodonos et al., 2014) have reported 
associations of PM10 during DDS outbreaks with increased hospital admissions for asthma, 
chronic obstructive pulmonary disease, cardiovascular disease and increased mortality. The 
pathogenic effect of PM inhalation has been attributed to direct physical and toxic action of 
particles on human airway epithelium and systemic inflammatory responses triggering 
endothelial dysfunction or dysfunction of the autonomic nervous system (Leski et al., 2011). 
Increased hospital admissions and mortality are only two of a much larger number of adverse 
outcomes of exposure to DDS PM. Beyond these serious complications, patients suffer 
symptomatic exacerbations of pre-existing conditions, require unscheduled hospital visits, use 
excessive medications, and lose their sense of well-being, often with days off work or school. 
These relatively less studied consequences are more common, but largely unquantified and 
un-investigated. Finally, DDS PM exposure is associated with sub clinical effects on the 
general population, from mild discomfort, eye and skin irritation to substantial effects on 
biological processes and quality of life. 
 

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Framework for designing, implementing and testing an adaptability strategy 
Our knowledge of the health risks associated with exposures to DDS PM in southern Europe 
comes mostly from small-scale local or national studies. Despite their limited scope, these 
investigations have provided sufficient evidence of a real human health risk affecting a large 
proportion of the EU population. Reversing the unfavourable climate trends that are 
exacerbating the effect of DDS in the region is a daunting task, and the benefits of global 
climate change policies will take decades to realize. 
 
At the moment, the EU national competent authorities and mass media in the DDS-exposed 
regions, during some of the events, issue not-standardised recommendations to the 
public/vulnerable groups, most commonly advising them to stay indoors, and reduce outdoor 
activities. To date, no scientific evidence exists on the effectiveness of any of these 
recommendations in either reducing the exposure to DDS PM or mitigating related health 
effects. The EU needs to develop evidence-based policies that increase individual, population, 
and institutional resilience to the growing frequency and intensity of DDS. We propose in 
three of the most heavily DDS-affected Mediterranean regions (Cyprus, Crete, and Israel) to 
apply, test and demonstrate the efficacy of patient-specific and population-wide public health 
interventions to reduce personal exposures to DDS as a means of adaptation. 
 
This study will address a significant knowledge gap in the health effects of personal exposures 
to desert dust particles, and establish vulnerability assessments in groups such as adults with 
AF and children with asthma, driven by our findings on the impact of the interventions on 
exposure, measures of health, and morbidity, thus enabling participant countries to build 
adaptation strategies and evidence-based policies. During and after the end of the project, this 
information and knowledge will be used to fine-tune tools for informed decision-making and 
strategic planning both at national (individual country stakeholders) and cross national levels 
and will be disseminated to facilitate an exchange of best practices and raise awareness within 
the population on their vulnerability to DDS pollutants as set out in EU policy priorities. 
 
 
3 
STUDY DESIGN 
 
Type of study: Public Health Intervention Study  
 
Children with asthma will be recruited during DDS outbreaks and will be randomized into 
three parallel groups to receive: 
a) No intervention for DDS, 
b) Intervention for outdoor exposure reduction, and  
c) Interventions for both outdoor and indoor exposure reduction. 
 
Disease-related adverse health outcomes will be assessed in all the parallel arms of the study. 

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Previous publications of the MEDEA partners (Achilleos et al, 2014; Gerasopoulos et al, 
2006; Krasnov et al, 2014), indicated that 2/3 of each year’s DDS events in the Eastern 
Mediterranean region appear during February-May, with 10-15% of the days during this 
period being “DDS days”. Thus, we will perform this panel study during February–May of 
2019 and 2020. 
 
Study population and location: Children with mild to moderate persistent asthma, aged 6-11 
years, will be recruited from primary schools in Nicosia-Cyprus (n=200), in academic years 
2018-2019 and 2019-2020. Each child will have assessment of health outcomes during only 
one high DDS period. 
 
Duration of the study: A feasibility trial and refinement of protocols and tools will be 
performed in the high DDS period of 2018. In fall 2018 and 2019, with the onset of academic 
year, screening survey questionnaires (International Study of Asthma and Allergies in 
Children, ISAAC) will be addressed to the parents of all children in 18-20 primary schools in 
Nicosia by the MEDEA personnel to detect eligible asthmatic children for participation in the 
study during the upcoming high DDS periods of February-May 2019 and 2020. 
 
Assessment of health outcomes: 
 Phone interviews at baseline and then at every 1 month throughout the high DDS 
period will be carried out, recording information on asthma medication use and 
unscheduled visits to health professionals for asthma.  
 Frequency of respiratory symptoms will be assessed via caregiver and child’s 
responses to questions on daytime and night-time symptoms in the past 4 weeks, with 
the help of a validated Greek version of the ACT. 
 Lung function, FeNO and specific aeroallergen sensitivities will be assessed at 
baseline, middle and end of high DDS season 
 
 
 
 
 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
 
4.1 Inclusion Criteria  
 
The inclusion criteria for this panel study will be children with physician-diagnosed asthma 
for at least one year and with at least one of the following: 
 Anti-asthma medication in the past year, 
 Wheezing in the past year, or 

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 An unscheduled medical visit for asthma in the past year. 
 
4.2 Exclusion Criteria  
 
Exclusion criteria will be:  
 Lung disease other than asthma 
 Cardiovascular disease 
 Not living at least 5 days per week in the household 
 
4.3 Study Enrollment Procedures  
 
Children with mild to moderate persistent asthma, aged 6-11 years, will be recruited at primary 
schools in Nicosia-Cyprus (n=150) in academic years 2018-2019 and 2019-2020. In order to 
facilitate recruitment, schools’ principals will be contacted individually at the beginning of 
each academic year and details of the study will be explained. Relations with the 
Administrative and Nursing staff of the Schools and Parents Associations will be established 
with the aim to facilitate field work. With the use of screening questionnaires (ISAAC 
questionnaires, see Appendices), parents will, after giving written consent (EKBK03, consent 
form 1, see Appendices), report their child's respiratory health information. Then the parents 
of children with asthmatic symptoms will be invited to participate in the MEDEA program 
after they give their written consent (EKBK03, consent form 2, see Appendices). For children 
participating in the program, consent to their participation will be given by their 
parents/guardians. Parents will be asked by the study personnel to read the respective consent 
forms for the survey and the study, and will be given the opportunity to ask any clarification 
questions for their child’s participation. 
. 
 
5 
STUDY INTERVENTIONS  
5.1 Interventions, Administration, and Duration  
 
Following the eligibility assessment, we will randomize participating schools (and their 
students with asthma) with a 1:1:1 ratio to three parallel groups to receive:  
a) no intervention for DDS 
b) intervention for outdoor exposure reduction, by reducing the time spend outdoors and 
by avoiding physical activity 
c) interventions for outdoor (as above) and indoor exposure reduction (by minimizing 
home ventilation and filtering indoor air). 
 

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In the indoor intervention arm of the study, exposure reduction measures will be applied in 
the asthmatic child’s classroom/school and bedroom/household settings. 
  
After randomization, the children, their parents and schoolteachers will be trained in the tools 
and procedures to be followed. 
 
Prior to the high DDS season, each eligible child will have at the school: 
 baseline demographic, medical, and symptom survey, and  
 assessments of lung function (Spirometry), fractional exhaled nitric oxide (FeNO), and 
specific aero-allergen sensitivities.  
 
The study design offers also the opportunity to assess: 
 outdoor exposures to PM,  
 indoor exposures to PM and  
 related health outcomes in three parallel groups during the same DDS events with and 
without intervention measures (Figure C7.1). 
 
 

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5.2 Handling of Study Interventions  
  
A bidirectional, patient-centered e-Platform will be created to: 
 Communicate promptly forecast alerts to individuals about upcoming DDS events 
through smartphone applications and text messaging 
 Disseminate exposure reduction guidelines 
 
In particular, in the group where there will be intervention for outdoor exposure reduction, the 
intervention will be carried out by: 
 
 Informing the participant and the parent for upcoming desert dust storm episodes. 
 Simultaneous transmission of instructions to a smartphone to reduce outdoor 

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exposure during the episode (stay indoors, avoid intense physical activity outdoors, 
avoid competitive sports, avoid unnecessary walks). 
 
In the group where there will be interventions for outdoor and indoor exposure reduction, the 
intervention will be carried out by:  
 
 Informing the participant and the parent for upcoming desert dust storm episodes. 
 Simultaneous transmission of instructions to a smartphone to reduce:  
a) Outdoor exposure during the episode (stay indoors, avoid intense physical 
activity outdoors, avoid competitive sports, avoid unnecessary walks) and 
b) Indoor, home and classroom exposure (closed windows and doors, sealing 
possible cracks around windows and doors in order to minimize home 
ventilation, and using an air cleaner in order to filter indoor air). 
 
 
5.3 Adherence Assessment  
 
The compliance to exposure-reduction guidelines will be monitored with the use of remote 
sensors. The intervention for outdoor exposure reduction, (by reducing the time spend 
outdoors and by avoiding physical activity) will be assessed with the use of smart 
wristwatches that will be equipped with Global Positioning System (GPS) and accelerometer. 
The intervention for indoor exposure reduction (by minimizing home ventilation and by 
filtering indoor air) will be assessed with the use of particle samplers that will be placed 
outside and inside of houses and school classrooms. 
 
 
 

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6 
STUDY PROCEDURES 
6.1 
Schedule of Evaluations 
 
 
Assessment 
Screening and 
Enrollment 
Baseline 
Assessment, and 
Randomization 
March 2019/2020 
Intervention 
mid-point 
assessment 
April 
2019/2020  
Intervention 
end-point 
assessment 
May 
2019/2020  
Informed Consent Form   
X 
 
  
  
Demographics 
X 
X 
  
  
Medical History  
X 
X 
  
  
House Assessment 
 
X 
 
 
Current Medications 
X 
X 
X  
X 
Intervention Discontinuation 
 
X 
X 
X 
Tel ACT Questionnaire 
 
X 
X 
X 
Lung function assessment 
 
X 
X 
X 
FeNO assessment 
 
X 
X 
X 
Specific aero-allergen 
sensitivities assessment 
 
X 
 
 
Adverse Events  
  
X 
X 
X 

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6.2 Description of Evaluations  
6.2.1 Screening and Enrollment Evaluation 
 
These evaluations will be performed to determine if the candidate is eligible for the study. 
 
Consenting Procedure 
 
Before any screening procedure is performed, informed consent must be obtained. There 
will be two consenting processes, one regarding the participation to the screening process 
and the final one which will regard full study enrollment.  
 
The survey consent form that describes the screening procedure will be given by 
classroom’s teachers to the children to take to their parents at home, whereas the second 
consent form for enrollment to the study will be handed by the study personnel to children’s 
parents directly.  
 
With the use of screening questionnaires (ISAAC questionnaires, see Appendices), parents 
upon written consent (EKBK03, consent form 1, see Appendices) will report their child's 
respiratory health data. Then parents of children with asthmatic symptoms will be invited 
to participate in the MEDEA program after they have given their written consent 
(EKBK03, consent form 2, see Appendices). Parents will be asked by the study personnel 
to read the consent form carefully and will be given the opportunity to ask clarification 
questions regarding the study and their child’s participation. Following a discussion with 
the parents, they will be asked to give their signed approval. The explanations given to the 
children will be in comprehensible non-technical terminology. 
 
Screening and Enrollment 
The screening procedure with the use of ISSAC questionnaires, will take place during fall 
2018 and 2019. The ISSAC questionnaire will allow for the collection of demographic, 
medical, medication and symptom data. The enrollment date is day the child participant 
has met all the screening criteria (both inclusion and exclusion criteria) and the parent signs 
the second informed consent form. 
 
6.2.2 Baseline, and/or Randomization 
 
Baseline Assessments 

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Participants who have been successfully screened for eligibility and are enrolled into the 
study, baseline assessments will be performed during January-February of each study 
year. Prior to the high DDS season, each eligible child at school will:  
a) Answer a questionnaire regarding socio-demographic characteristics 
b) Provide detailed medical and medication history (frequency of respiratory symptoms 
will be assessed via caregiver and child’s responses to questions on daytime and 
nighttime symptoms in the past 4 weeks, with the help of a validated Greek version 
of ACT, asthma medication use, unscheduled visits to health professionals for 
asthma) 
c) Have household characteristics assessments  
d) Have assessments of lung function (Spirometry), fractional exhaled nitric oxide 
(FeNO), and specific aero-allergen sensitivities. 
 
 
Randomization 
 
Following the eligibility assessment and prior to the baseline visit, participating schools 
(and their students with asthma) will be randomized using standard computer software 
(Microsoft Excel) that allows for random number generation. Randomization will be 
carried out with a 1:1:1 ratio to three parallel groups: 
a) Control group A: No intervention for DDS,  
b) Intervention group B: Intervention for outdoor exposure reduction, and  
c) Intervention group C: Interventions for outdoor and indoor exposure reduction 
(asthmatic child’s classroom/school and household/bedroom settings). 
 
 
6.2.3 Follow-up Assessments 
 
  Intervention mid-point assessment April 2019/2020: 
o Current medications 
o Intervention discontinuation 
o Telephone ACT questionnaire (monthly) 
o Lung function assessment 
o FeNO assessment 
o Specific aero-allergen sensitivities 
o Adverse events 
 
 

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6.2.4 Completion/Final Evaluation 
 
 Intervention end-point assessment May 2019/2020: 
o Current medications 
o Intervention discontinuation 
o Telephone ACT questionnaire (monthly) 
o Lung function assessment 
o FeNO assessment 
o Specific aero-allergen sensitivities 
o Adverse events 
 
7 
ASSESSMENTS OF ADVERSE EVENTS  
 
Since, the intervention under study is behavioral/lifestyle intervention, it does not involve 
any specific drug administration nor any change in ongoing medication regimen. 
Furthermore, it does not include any invasive procedure and all the health outcomes are 
assessed using non-invasive methods (smart-watches, phone interviews) and questionnaires. 
Hence, there are no specific safety parameters to quantify adverse health events related to 
interventions. 
 
At any point during the study, patients will have the opportunity to bring any information or 
issue (e.g. health issue) that concerns them to the attention of the primary investigator, Dr 
Panayiotis Yiallouros, whose contact information will be given to all participants during the 
enrollment phase, and will also be available on the program's website. 
 
 
8 
INTERVENTION DISCONTINUATION  
 
Subjects may withdraw voluntarily from the study at any time and for any reason. 
 
Parents or guardians of asthmatic children can make oral complaints to members of the 
research team as well as to the principal investigators of each site. 
 
The criteria for discontinuation of intervention will be: 
 Non-adherence to the intervention 
 Moving to a different house than the reported initial one 
 Moving to a different school 

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 Significant change in health status 
 
 
9 
DATA COLLECTION  
9.1 Data Collection Forms 
 
Health assessment data: 
 The baseline demographic (gender, age, city), medical, medication and symptom data 
will be obtained using surveys/questionnaires (ISAAC). 
 The lung function will be assessed using portable spirometers. 
 The fractional exhaled nitric oxide (FeNO) will be assessed using handheld fractional 
exhaled nitric oxide analyzers (NIOX VERO). 
 Specific aero-allergen sensitivities will be assessed with skin prick testing. 
 Frequency of respiratory symptoms will be assessed via caregiver and child’s 
responses to questions on daytime and nighttime symptoms in the past 4 weeks, with 
the help of a validated Greek version of the ACT. 
 Information will also be obtained on asthma medication use and unscheduled visits 
to health professionals for asthma via phone interviews. 
 
Exposure data:  
 Household characteristics will be assessed with the help of a questionnaire at the 
onset of the study. 
 Real time location data will be assessed using personal smartphones application for 
The Global Positioning System (GPS), satellite-based navigation system installed 
in every smartphone.  
 Real time location data from the GPS will be coupled with accelerometer data from 
smart wristwatches.  
 Hourly central data on air pollutants, including; ambient concentrations of PM10, 
PM2.5, as well as meteorological factors (temperature and relative humidity). 
 Outdoor and indoor PM and chemicals at participants’ households and school will 
be assessed with outdoor and indoor samplers. 
 
9.2 Data Management  
The study will be overseen and managed by the Medical School, University of Cyprus, under 
the supervision of the LIFE+ MEDEA principal investigator, Professor Panayiotis 
Yiallouros.  

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All collected data, will be analyzed and discussed between LIFE+ MEDEA partners only by 
using codes to ensure that the anonymity of the participants is fully preserved. 
 
 
 
10 PARTICIPANT RIGHTS AND CONFIDENTIALITY  
 
Patients and their parents/guardians will be informed about the program and the data to be 
acquired through the information material that will be provided with the consent form. 
 
During the study, patients will have the opportunity to get any additional information on any 
subject that concerns them from the study personnel and/or the principal investigator (project 
coordinator) Prof. Panayiotis Yiallouros whose contact information will be given to all 
participants during the recruitment process and will also be available on the program's 
website. 
 
Also, relevant conclusions resulting from the collected data analysis will be communicated 
to patients at the end of the program. This information will concern the better monitoring and 
forecasting of dust storms and the results of the interventions in order to reduce exposure of 
the population to DDS events. 
 
10.1 Informed Consent Forms 
A signed consent form will be obtained from each participant. The consent form will describe 
the purpose of the study, the procedures to be followed, and the risks and benefits of 
participation. A copy will be given to each participant or legal guardian and this fact will be 
documented in the participant’s record.  
 
10.2 Participant Confidentiality  
Administrative safeguards: 
Data will be completely anonymized and encrypted prior to sending to the central database. 
The full record of Cypriot asthmatic children with names, addresses, and other personal 
information will be kept by the principal investigator Prof. Panayiotis Yiallouros at the 
Medical School of the University of Cyprus and only authorized personnel will have access 
to this data (Panayiotis Kouis). All data to be collected, will be analyzed and discussed 
between program partners only by using codes (a participant identification number 
(Participant ID, PID) to ensure that the anonymity of the participants is fully preserved and 
to maintain confidentiality. 

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Technical safeguards: 
Electronic access to Cypriot patient data will require a user name and password that will only 
be held by authorized personnel. All computer entry and networking programs will be done 
using PIDs only. In addition, the Microsoft Azure storage platform that will be used for the 
purpose of data storage and backup, is Health Insurance Portability and Accountability Act 
(HIPAA) compliant, that establishes requirements for the use, disclosure, and safeguarding 
of individually identifiable health information. 
The University of Cyprus has a policy that requires computer users not to leave computers 
unattended and not to exchange entry codes between them. Still, it is worth mentioning that 
after a few hours of non-use, the computer automatically turns off and locks again, requiring 
the use of the input code again. 
In the event that a computer containing personal data is no longer used, the University of 
Cyprus will ensure that the data will either be transferred or destroyed. 
 
Physical safeguards: 
The Medical School of the University of Cyprus is housed in the Shakolio Educational 
Center, a safe building on Nicosia-Limassol Old Road, in Aglantzia, Nicosia. 
The building is protected internally and with the supervision of the surrounding area, on a 
daily basis with a 24-hour security guard. The guard checks all incoming people in the 
building. 
Data that may be in print will be kept in a closet in the office of the Project Coordinator so 
that no unauthorized person has access to them. 
All records will be kept in a locked file cabinet.   
 
11 ETHICAL CONSIDERATIONS 
 
The study has already obtained permission from the Cyprus National Bioethics Committee. 
The intervention under study meets the criteria of the Helsinki declaration and follows the 
ICH/GCP and EC rules of good clinical practice. Data from individual countries will be 
completely anonymized and encrypted prior to sending to the central database. 
 
There are no significant ethical considerations, since all necessary safeguards will be taken so 
that all participants do not face any risk and their personal data are protected. Participation 
will be on a voluntary basis and all participants will be able to withdraw at any point in the 
program. 
 
 

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12 COMMITTEES 
 
Steering Committee: 
The Steering Committee will scrutinize the quality of the project performance and will act 
as a supervisory body to ensure that the work described in individual actions is carried out. 
The members of the steering committee will include the Project Coordinator, Project 
Manager, and the Leaders of all other project partners (Soroca Clinical Research Center, 
University of Crete, Cyprus University of Technology, E.n.A. Consulting, Department of 
Labor Inspection, Cyprus Broadcasting Corporation, Cyprus Department of Meteorology). 
The Steering Committees will be responsible for the: 
 Decisions on technical roadmaps for the project and monitoring 
implementation; 
 Provision of data for preparation of reports and deliverables to the 
Commission. 
 
External Advisory Committee: 
The external advisory committee will be responsible to counsel the project and to help 
transform our results to policies. The advisory committee will consist of relevant regulatory 
authorities and interested social stakeholders. There will be in total 30 members from all 
participating sites, i.e. ~10 members from each site. 
 
13 REFERENCES 
 
 
Achilleos S, et al. PM10 concentration levels at an urban and background site in Cyprus: the impact 
of urban sources and dust storms. J Air Waste Manag Assoc 2014; 64:1352-60. 
 
Gerasopoulos E, et al. Origin and variability of particulate matter (PM10) mass concentrations over 
the Eastern Mediterranean. Atmos Environ 2006; 40:4679-4690.  
 
Griffin D. Atmospheric movement of microorganisms in clouds of desert dust and implications for 
human health. Clin Microbiol Rev. 2007; 20:459-77. 
 
Krasnov H, et al. Contribution of dust storms to PM10 levels in an urban arid environment. J Air 
Waste Manag Assoc 2014; 64:89-94. 
 
Leski T, et al. Application of a broad-range resequencing array for detection of pathogens in desert 
dust samples from Kuwait and Iraq. Appl Environ Microbiol 2011;77:4285-92. 
 
Mallone S, et al. Saharan dust and associations between particulate matter and daily mortality in 
Rome, Italy. Environ Health Persp 2011; 119:1409–1414. 
 
Middleton N, et al. A 10-year time-series analysis of respiratory and cardiovascular morbidity in 
Nicosia, Cyprus: the effect of short-term changes in air pollution and dust storms. Environ Health 
2008; 22;7:39. 
 
Neophytou A, et al. Particulate matter concentrations during desert dust outbreaks and daily 
mortality in Nicosia, Cyprus. J Expo Sci Environ Epidemiol. 2013; 23:275-80. 
 
Querol X, et al. African dust contributions to mean ambient PM10 mass-levels across the 
Mediterranean, Basin. Atmos Environ 2009; 43:4266-4277. 

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 
Samoli E, et al. Acute effects of air pollution on pediatric asthma exacerbation: evidence of 
association and effect modification. Environ Res 2011;111:418-24. 
 
Vodonos A, et al. The impact of desert dust exposures on hospitalizations due to exacerbation of 
chronic obstructive pulmonary disease. Air Qual Atmos Health 2014; 7:433–439. 
 
14 SUPPLEMENTS/APPENDICES 
 
I. Informed Consent Form Templates  
A. Informed Consent Form Templates – Consent Form 1(screening) 
B. Informed Consent Form Templates – Consent Form 2 (enrolment) 
 
 
 
 
 
 
 
 
 
 
 
 

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