Vascular Implications of a Naturally Occurring Asthma Exacerbation
Conditions: Asthma, Inflammation, Cardiovascular Risk Factor
Sponsor: University of Alberta

Adapted from the Grand Rapids Medical Education and Research Center 
 
Vascular Implications of a Naturally Occurring Asthma Exacerbation 
 
 
 
 
Authors: 
Dr. Michael Stickland, PhD1; Shelby Henry, BKin2.  
 
 
Institutions: 
1Department of Medicine, Faculty of Medicine and Dentistry 
2Faculty of Rehabilitation Medicine 
 
Corresponding 
Author: 
Dr. Michael Stickland, PhD 
Department of Medicine 
3-135 Clinical Sciences Building 
University of Alberta 
Edmonton, Alberta 
Canada 
T6G 2J3 
Ph. 780-492-3995 
Fax. 780-492-4483 
Email: michael.stickland@ualberta.ca 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL 
This document is confidential and the property of individual.  No part of it may be transmitted, reproduced, 
published, or used by other persons without prior written authorization from the author. 
Protocol/version #:  Pro00083372 
Current Version Date: October 12, 2018 
 
Previous IRB Approved Version Dates: 
n/a 
 

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List of Abbreviations 
 
ANOVA 
Analysis of Variance  
 
ACQ  
Asthma Control Questionnaire 
 
AQLQ  
Asthma Quality of Life Questionnaire 
 
CRP 
 
C - reactive protein 
 
CV 
 
Cardiovascular 
 
ED 
 
Emergency Department 
 
EMeRG 
Emergency Medicine Research Group 
 
EQ-5D  
EuroQol 5 Dimensions 
 
FEV1  
Forced Expiratory Volume in the first second 
 
FMD  
Flow-mediated dilation (% baseline) 
 
FVC  
Forced Vital Capacity 
 
HR 
 
Heart Rate 
 
HREB  
Health Research Ethics Board 
 
IL-17  
Interleukin-17 
 
PFT 
 
Pulmonary Function Test 
 
PWV  
Pulse wave velocity (m/s) 
 
SSRH  
Shear Stress during Reactive Hyperemia 
 
VRH  
Velocity during Reactive Hyperemia 
 
VTI 
 
Velocity Time Integral 
 
 

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Table of Contents 
 
1 
INTRODUCTION/SIGNIFICANCE ............................................................................................................... 4 
2 
STUDY OBJECTIVES ...................................................................................................................................... 4 
3 
PATIENTS AND METHODS ........................................................................................................................... 5 
3.1 
STUDY DESIGN ............................................................................................................................................. 5 
3.1.1 
General Design.................................................................................................................................... 5 
3.1.2 
Primary Outcome Variable ................................................................................................................. 6 
3.1.3 
Secondary Outcome Variables ............................................................................................................ 6 
3.2 
SUBJECT SELECTION AND WITHDRAWAL ...................................................................................................... 6 
3.2.1 
Inclusion Criteria ................................................................................................................................ 6 
3.2.2 
Exclusion Criteria ............................................................................................................................... 6 
3.3 
STUDY PROCEDURES ..................................................................................................................................... 6 
3.4 
STATISTICAL PLAN ....................................................................................................................................... 9 
3.4.1 
Sample Size Determination .................................................................................................................. 9 
3.4.2 
Statistical Methods .............................................................................................................................. 9 
4 
DATA HANDLING AND RECORD KEEPING .......................................................................................... 10 
4.1 
CONFIDENTIALITY ...................................................................................................................................... 12 
4.2 
RECORDS RETENTION ................................................................................................................................. 12 
5 
STUDY AUDITING AND INSPECTING ..................................................................................................... 12 
6 
BUDGET ........................................................................................................................................................... 12 
7 
PUBLICATION PLAN .................................................................................................................................... 12 
8 
REFERENCES ................................................................................................................................................. 12 
9 
ATTACHMENTS ............................................................................................................................................ 15 
 

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1  Introduction/Significance 
This document is a clinical research protocol and the described study will be conducted in 
compliance with the protocol, Good Clinical Practices standards and associated Federal 
regulations (i.e. Health Canada), and all applicable institutional research requirements. 
 
Asthma is a chronic inflammatory disease characterized by pulmonary inflammation and 
bronchoconstriction, with the prevalence of asthma is steadily rising worldwide1. Asthma and 
Cardiovascular Disease:  While asthma is generally considered to be a disease of the airways, 
there are important systemic consequences which have predisposed people with asthma to 
become more likely to die from cardiovascular (CV) disease compared to non-asthmatics2. 
Additional CV risks have been reported in people with severe asthma3, and there is a relationship 
between reductions in lung function and cardiac death4. To date, little is known in regards to the 
interaction between asthma exacerbations and CV risk. Asthma and vascular dysfunction: 
Brachial flow-mediated dilation (FMD) is used as a non-invasive tool to evaluate endothelial 
function5. Brachial FMD is impaired in people with coronary dysfunction6, and can predict 
future CV events better than traditional CV risk factors7. People with asthma have previously 
been shown to have impaired endothelial function compared to non-asthmatics8, but the 
underlying mechanism(s) are unclear. Asthma, systemic inflammation, and CV risk: Chronic 
systemic inflammation is an established risk factor and predictor of future CV events9, and levels 
of systemic inflammation are increased in asthma10,11. Furthermore, while people with high 
levels of inflammation are more likely to suffer both first time and recurrent cardiac events12,13, 
levels of systemic inflammation in asthma are related to disease severity and are the highest 
during asthma exacerbations10,11. Previous studies have shown that systemic inflammation 
directly impairs vascular function14, and rodent work has shown that pulmonary inflammation 
can impair vascular function15. To-date, no study has examined how an asthma attack may affect 
vascular function and CV risk. Thus, to gain better understanding of the increased CV risks 
associated with asthma exacerbations, the aim of this study is to evaluate vascular function and 
systemic inflammation during a naturally occurring asthma exacerbation.  
 
If this study finds a large systemic inflammatory insult as well as significant vascular 
dysfunction, as a result of an asthma exacerbation, this could have strong clinical implications. 
This research would highlight the importance of preventing an asthma exacerbation based on the 
significant negative impact that an acute exacerbation may have on the cardiovascular system. 
Future research on pulmonary rehabilitation for asthma could target reducing systemic 
inflammation and improving vascular function, as well as changes to current guidelines and 
recommendations for people with asthma to reflect the necessity of reducing systemic 
inflammation and improving vascular function to reduce CV risk. 
 
2 Study Objectives 
 
Primary Objective 
To examine the endothelial function of an individual experiencing a naturally occurring asthma 
exacerbation. 
 

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Secondary Objective 
To examine the arterial stiffness and systemic inflammation of an individual experiencing a 
naturally occurring asthma exacerbation. 
3 Patients and Methods 
3.1 Study Design 
3.1.1 General Design 
This study is a cohort study utilizing a repeated measure design. Asthmatic patients will be tested 
at 3 different time points: 
 At the emergency department 
 48 hours following discharge 
 14 days following discharge 
 
Stable asthmatic and non-asthmatic controls will be tested at two time points: 
 Day 1 
 48 hours following Day 1 
 
Vascular parameters such as flow mediated dilation (FMD; endothelial function) and pulse wave 
velocity (PWV; arterial stiffness) will be evaluated at each time point to assess vascular function. 
Blood samples will be obtained for analysis of systemic inflammatory response and immune 
response at each time point. 
 
Participants will also be given Fitbit activity monitors for 7 days of monitoring, perform a full 
pulmonary function test (PFT) and complete 3 questionnaires; Asthma Control Questionnaire 
(ACQ), Asthma Quality of Life Questionnaire (AQLQ), and EQ-5D. 
 
(A) Cohort studies  
 
Definition of study groups:  
Individuals experiencing an asthma exacerbation will be identified at the University of 
Alberta Emergency Department (ED). They will be recruited based on asthma being the 
primary physician diagnosis in the ED, with asthma being confirmed at a follow up visit 
using spirometry. 
 
Stable asthmatic controls will be recruited from the general populations, as well as two local 
pulmonary clinics: The Lung Health Clinic, Edmonton, AB; and the University Lung Clinic, 
Edmonton, AB. These participants will be recruited if they have indicated they have been 
diagnosed with asthma. Both confirmed and unconfirmed asthmatics will be eligible.  
 
Healthy controls will be recruited from the general population. They will be age-, sex, and 
BMI matched to the exacerbation group. 
 
Blinding and avoiding bias:  
Due to the nature of the study, blinding will not be applicable.  

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3.1.2 Primary Outcome Variable 
Flow-mediated dilation (FMD) of the brachial artery following 5 minutes of forearm occlusion 
will be measured using our ultrasound machine (8L-RS 4.0-13.0 MHz probe, Vivid q, GE 
Healthcare, Mississauga, ON) and FMD data will be analyzed using FDA approved software 
available from Medical Imaging Applications (Coralville, IA, USA). FMD will be calculated as: 
(peak hyperemic diameter-baseline diameter)/baseline diameter x 100.  Peak hyperemic brachial 
arterial velocity (and subsequently shear stress) will be determined using Doppler ultrasound, 
and used for normalization of FMD.  
3.1.3 Secondary Outcome Variables 
Arterial stiffness will be assessed using tonometry (Complior, Alam Medical, Saint Quentin 
Fallavier, France) and reported as PWV in m/s. Arterial stiffness will be determined using 
carotid – radial pulse wave velocity (PWV), and PWV will be calculated from measurements of 
pulse transit time and the distance traveled by the pulse between recording sites. Systemic 
inflammation and immune response will be assessed via antecubital venipuncture and analyzed 
at the University of Alberta. Based on prior research, important biomarkers have been identified 
as being involved in the inflammatory process of asthma, and are useful in identifying specific 
atopic phenotypes.16 The biomarkers being analyzed will include C-reactive protein (CRP), 
eosinophils, neutrophils, periostin, interleukin-17 (IL‐17), YKL‐40, and specific 
immunoglobulin E (IgE). 
3.2 Subject Selection and Withdrawal 
3.2.1 Inclusion Criteria 
To be eligible for this study, the participants have to be between the ages of 18 and 55. 
Asthmatics will have to present at the ED with an apparent asthma exacerbation. Stable asthma 
controls may have confirmed or unconfirmed asthma. Healthy control participants must be free 
of asthma.  
3.2.2 Exclusion Criteria 
Participants who at the time of the study have known heart failure or unstable cardiac disease, 
lung diseases other than asthma, current infections, smoking history > 10 pack years, or known 
metabolic conditions will be excluded from this study.  
3.3 Study Procedures 
 
Asthmatic patients will be tested at three different times:  
 Day 1) ED visit 
 Day 2) 48 hours post discharge 
  Day 3) 14 days’ post discharge  
 
Day 1, participants will be recruited by the Emergency Medicine Research Group (EMeRG). 
They will receive standard emergency care for their asthma and once stabilized, informed 
consent will be obtained. A venous blood draw will be done prior to discharge. Once stabilized, 
the participant will be taken to a private area either within the ED department or Dr. Stickland’s 

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lab in Clinical Sciences Building to ensure no interference with ED procedures. Applanation 
tonometry will be done to measure PWV, followed by FMD to determine endothelial function. 
Day 2 the participant will return and the same assessments as Day 1 will be performed with the 
addition of spirometry according to standardized guidelines.18 Medication will not be withheld 
prior to this assessment. A Fitbit will be given along with instructions to wear the device for 7 
days.  
Day 3 will consist of the same measurements done in the ED for Day 1, with the addition of 2 
quality of life questionnaires, the standardized Asthma Quality of Life Questionnaire (AQLQs) 
and the EQ-5D (5L), and the Asthma Control Questionnaire (ACQ), finishing with a full 
pulmonary function test including post-bronchodilator spirometry to evaluate for airway 
reversibility (i.e. asthma)19.  
 
The participants are being tested 48 hours following the exacerbation to determine if systemic 
inflammation is further increased following an exacerbation, or if the exacerbation is when 
inflammation is at its peak. This will inform us on whether the exacerbation itself is the stimulus 
for increased systemic inflammation, or if it is a consequence of a stimulus in the days prior. The 
14 day follow up was chosen based on the information that CRP is generally recovered to normal 
values after 14 days following stimulus,20 as well, it is expected that lung function will have 
recovered 14 days following an exacerbation, as seen in other pulmonary disease 
exacerbations.21 Day 3 will tell us what average values for the participant would most likely be 
and allow us to compare the values obtained from the exacerbation against a personal reference 
value. 
 
Stable asthmatics and healthy control participants will be tested at two different times: 
 Day 1) date that participant is available for testing 
 Day 2) 48 hours after Day 1 
 
Controls are being tested at two times to determine the degree of natural fluctuations in 
endothelial function, arterial stiffness, and systemic inflammation in healthy adults.  
 
Measurements 
 
Waist Circumference – Using a fabric tape measure, waist circumference will be measured at the 
level of the last rib to the nearest 0.1 cm after a normal expiration.17 This will be used as a 
measure of adiposity and will potentially be used as a covariate during statistical analysis. 
   
Arterial stiffness - Arterial stiffness will be evaluated using pulse wave velocity (PWV) between 
the carotid and femoral arteries. After 10 minutes of resting in a dark, quiet room in the supine 
position, cPWV and pPWV will be recorded using applanation tonometry (Complior, Alam 
Medical, Saint Quentin Fallavier, France). A series of 10 consecutive beats will be taken with a 
minimum quality of 85%. The distance between the carotid and femoral artery, as well as the 
carotid and radial artery will be recorded in mm. PWV will be measured prior to FMD and blood 
collection, and will be taken on all 3 days of assessments. PWV is expressed as m/s and is 
calculated as PWV= L/∆t, with L being the distance between the two points and ∆t being the 
time it takes for the pulse to get from site 1 to site 2.22 
 

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Endothelial function - The endothelial function of the brachial artery will be evaluated after 10 
minutes of rest in the supine position using ultrasound imaging (8L-RS 4.0-13.0MHz probe, 
Vivid q, GE Healthcare, Mississauga, ON). Baseline diameter of the brachial artery will be 
established, whereby the blood flow of the forearm will be occluded distal to the measuring site 
for the duration of 5 minutes. Upon release of the occlusion, the blood velocity and the brachial 
diameter will be monitored for 3 minutes, and later analyzed (Medical Imaging Applications, 
LLC, Coralville, IA, USA; EchoPAC PC software, version 110.x.x, GE Healthcare, Horten, 
Norway). Microvascular function will be evaluated as the velocity time integral-envelope of the 
first heartbeat of reactive hyperemia (VTI; m/s) and the velocity during reactive hyperemia 
(VRH) calculated as VTI x 60/HR.23 Shear stress during reactive hyperemia (SSRH) will 
subsequently then be calculated as SSRH = 8 x flow / diameter and as cumulative SSRH until the 
time of peak FMD%.24,25 FMD corrected for SSRH will be considered the main outcome for 
endothelial function in this study, and VRH and SSRH as indicators of microvascular function. 
Follow up tests will be conducted after a 12 hour fasting period when possible. Where 
applicable, the subjects will be asked to withhold any long-acting asthma medication for a 
minimum on 48 hours prior to the test, and short-acting asthma medications for 12 hours prior to 
the test. 
 
 
Systemic inflammation and immune response – Serum CRP, IgE, periostin, YKL-40 and whole 
blood eosinophils, neutrophils, and IL-17 will be analyzed from venous blood collected at each 
assessment day at the end of the visit via antecubital venipuncture by a certified phlebotomist 
following specified guidelines.26 With the participant sitting in a relaxed position, the upper arm 
will be occluded to increase the accessibility of the blood vessels. Once a vein is chosen (based 
on proximity to the surface, size, position and absence of scar tissue and/or pulsation), a sterile 
25-gauge needle will be inserted at a 30-degree angle or less to initiate blood draw. Blood will be 
collected in anti-coagulant-free polypropylene tubes pre labeled with the participant’s 
identification number, date and time, and visit number. After two tubes are collected, the 
tourniquet will be removed followed by the needle and pressure will be applied to the 
venipuncture site and held until the bleeding stops. Once collected, the blood will be left to clot 
for a minimum of 30 minutes followed by centrifuging at 1000g for 10 minutes at 4 degrees 
Celsius. The serum will be separated into aliquots of 75 µg immediately after centrifuging and 
then stored at -80 degrees Celsius until analysis. Analysis of inflammatory and immune markers 
will be completed at the University of Alberta. 
 
 
Physical activity - Physical activity will be evaluated by step count using a Fitbit activity monitor 
(Fitbit Inc., San Francisco, CA). Participants will be instructed to wear the monitor on their wrist 
for 7 days, beginning the morning after Day 2 testing. It will only be removed to shower/bathe 
and to sleep. Total steps in each 24-hour period will be averaged and used to determine activity 
levels during the first week of recovery. Low active will be defined as <7,500 steps/day. 
Somewhat active will be defined as 7,500-9,999 steps/day. Active will be defined as > 10,000 
steps/day.27 
 
Pulmonary function – all participants will undergo a full pulmonary function test, according to 
established clinical guidelines.19,20 The expiratory volume in 1 second (FEV1) responses to 

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4x100 mg Salbutamol will be evaluated, and an increase in FEV1 of ≥ 12% and 200 ml will be 
considered positive for significantly reversible airway constriction.28  
 
Questionnaires – The participant will be asked to complete the Asthma Control Questionnaire 
(ACQ) to assess asthma control. The ACQ is a validated, simple 7 item questionnaire that asks 
questions regarding symptoms and rescue inhaler use in the last week.29 The minimally 
important difference for the ACQ is 0.5 with scores ranging from 0 (totally controlled) to 
6(severely uncontrolled).30 Next the participant will be asked to fill out the standardized Asthma 
Quality of Life Questionnaire, which is a validated, disease specific health-related quality of life 
assessment that encompasses both physical and emotional impacts of asthma.31 This 
questionnaire contains 32 items across 4 domains, with a minimally important difference of 0.5 
with scores ranging from 1-7 with higher scores representing better quality of life.32 Lastly, the 
EQ-5D (5L) will be completed by the participant to assess their generic health status and all 
related aspects in their quality of life.33 The EQ-5D (5L) is a validated and reliable questionnaire 
consisting 5 domains, along with a visual scale to measure the participants own judgement on 
current health status.34 Together, these questionnaires will give us a representations of the 
individuals experience with asthma, along with the physical 
 
3.4 Statistical Plan 
3.4.1 Sample Size Determination 
While the impact of asthma exacerbations on vascular function is currently unknown, we based 
our sample size calculation on our preliminary VTI data from 11 confirmed asthmatics who 
underwent a mannitol airway challenge to induce airway inflammation and bronchoconstriction. 
Based on these data, a total of 36 asthmatics and 36 controls in each group (stable asthma, 
healthy) would be sufficient to detect a 13% difference between these groups in VTI. Our 
preliminary data show a large increase in CRP in asthmatics experiencing an exacerbation vs. 
stable patients (7.3 vs. 0.5 mg/L, p<0.05), which would correspond to a substantial increase in 
CV risk35, and be detectable with this sample size. An additional 8 participants per group will be 
recruited (i.e. 44 asthmatics, 44 stable asthmatics, and 44 controls) to compensate for potential 
dropouts. Sub-analyses evaluating potential sex-based differences will be exploratory and results 
will be considered hypothesis-generating. 
3.4.2 Statistical Methods 
The mean differences in FMD, systemic inflammation, and arterial stiffness for ED visit 
compared to the control group will be evaluated using an unpaired t-test. A within-factors 
repeated measures analysis of variance (ANOVA) will evaluate the mean differences between 
each assessment day for the exacerbation group to assess change in endothelial function during 
exacerbation as well as the recovery period. A similar evaluation will be used for arterial 
stiffness and systemic inflammation/immune response. A one-way analysis of covariance 
(ANCOVA) will be used to correct for shear rate in FMD for all groups, with both values being 
reported. An α-level of 0.05 will be used as the significance level for all statistical analysis, and 
all results will be reported as mean ± standard deviation unless indicated otherwise. 

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4 Data Handling and Record Keeping 
 
Data to be collected:  
 
Outcome variables:  
 
Endothelial function 
Source of the data: Flow-mediated dilation test (see measurement, endothelial function above).  
Time point for collection: Collected as the last assessment during the ED visit. For the 2 follow 
up visits, FMD will be done after arterial stiffness and prior to blood draw.   
Who will collect the data: All data will be collected by trained research staff associated with the 
study.  
Why the data is being collected: To evaluate the influence of acute asthma exacerbation on 
vascular health. 
Is the data from a standardized tool: Yes.  
What form will the data will take (e.g. binary, continuous (numeric), time to event): Continuous.  
 
Arterial stiffness 
Source of the data: pulse wave velocity test (see measurements, arterial stiffness above). 
Time point for collection: At the ED, arterial stiffness will be collected after blood draw and 
prior to endothelial function. At the follow up visits, it will be collects as the primary assessment. 
Who will collect the data: All data will be collected by trained research staff associated with the 
study.  
Why the data is being collected: To evaluate the influence of acute asthma exacerbation on 
vascular health. 
Is the data from a standardized tool: Yes.  
What form will the data will take (e.g. binary, continuous (numeric), time to event): Continuous.  
 
Systemic inflammation and immune response 
Source of the data: Venous blood samples (see measurements, systemic inflammation and 
immune response above). 
Time point for collection: At ED, blood will be collected as the primary assessment. At follow up 
visits, it will be collected as the final assessment.   
Who will collect the data: All data will be collected by trained research staff associated with the 
study.  
Why the data is being collected: To evaluate changes in systemic inflammatory levels and 
immune response throughout the study.  
Is the data from a standardized tool: Yes.  
What form will the data will take (e.g. binary, continuous (numeric), time to event): Continuous.  
 
Explanatory variables and potential cofounding variables:  
 
Participant demographics, health history, and current status 
Source of the data: interview with the participant as well as medical chart and ED physician. (see 
appendix 5) 

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Time point for collection: in the ED once hemodynamically stable and while receiving treatment. 
At follow up visits, additional information will be collected prior to assessments.  
Who will collect the data: All data will be collected by trained research staff associated with the 
study.  
Why the data is being collected: To ensure subject meet the inclusion/exclusion requirements, to 
obtain information on potential confounding variables, and to obtain general sample 
characteristics.  
Is the data from a standardized tool: No, demographics will be collected according to the data 
collection document provided.  
What form will the data will take (e.g. binary, continuous (numeric), time to event): Nominal, 
continuous or ordinal.  
 
Perceived level of control and quality of life 
Source of the data: The asthma control questionnaire (see appendix 1), asthma quality of life 
questionnaire (see appendix 2), and EQ-5D (see appendix 3). 
Time point for collection: at 14 day post-discharge follow up.  
Who will collect the data: All data will be collected by trained research staff associated with the 
study.  
Why the data is being collected: To evaluate the current levels of perceived asthma control, 
disease specific quality of life and generalized quality of life. 
Is the data from a standardized tool: Yes.    
What form will the data will take (e.g. binary, continuous (numeric), time to event): Continuous.  
 
Lung function 
Source of the data: Pulmonary function test (see measurements, pulmonary function above) 
Time point for collection: during a pre-test session, and at each baseline time-point.  
Who will collect the data: All data will be collected by trained research staff associated with the 
study.  
Why the data is being collected: To evaluate baseline lung function at each study day.  
Is the data from a standardized tool: Yes.    
What form will the data will take (e.g. binary, continuous (numeric), time to event): Continuous.  
 
Physical Activity 
Source of the data: Fitbit activity monitor  
Time point for collection: monitor given at end of 48 hour follow up and retrieved from 
participant at 14 day follow up.  
Who will collect the data: All data will be collected by trained research staff associated with the 
study.  
Why the data is being collected: To evaluate average physical activity levels.  
Is the data from a standardized tool: Yes.    
What form will the data will take (e.g. binary, continuous (numeric), time to event): Ordinal. 
 
Data collection forms and questionnaires are included as appendices. 

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4.1 Confidentiality 
Each research participant will be assigned a study ID which will not be associated with any 
personal identifiable information. All collected study data will be stored either on password 
protected computer hard drives or in locked filing cabinets.     
4.2 Records Retention 
All data will be stored for 5 years following the completion of the study, whereby it will be 
destroyed.  
5 Study Auditing and Inspecting 
Not applicable.  
6 Budget  
For complete budget, please see appendix 4.  
Budget summary: 
Salaries and Benefits 
$14,985  
Materials and Supplies 
$15,098  
Payment to Subjects 
$10,780  
Publications 
$1,000  
TOTAL BUDGET  
$41,863  
7 Publication Plan 
Upon completion, this study is expected to be published as a peer-reviewed research article. A 
portion of the data from this study will be used for a MSc Thesis.   
 
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Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. 
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9 Attachments 
 
Appendix 1. Asthma Control Questionnaire (used with permission from creator).  
 
 
 
 

Adapted from the Grand Rapids Medical Education and Research Center 
Appendix 2. Asthma Quality of Life Questionnaire (used with permission from creator). 
 

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Appendix 3. EQ-5D (used with permission from creator).
 
 

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Appendix 4. Budget 
1. Salaries and Benefits 
Research Assistant: Funds are requested for the salary one research assistant (0.25 full-time 
equivalents, FTE). This person will assist with data collection for all aims and ensure quality 
control of all data collection and data analysis.  
FTE  
1.0 
0.25 
Salary (Grade 6, Step 5): 
$46,155 
$11,539 
Benefits (23%):  
$13,786 
$3,447 
Total Salaries and Benefits 
 
$14,985 
 
2. Material and Supply 
Systemic Inflammatory Markers: Venous blood will be collected and processed for whole 
blood and serum analysis at each assessment for asthmatics and controls (3 assessments (asthma) 
X 44 participants + 2 assessments(controls) X 44 participants= 220 samples) for analysis of 
serum CRP, IgE, periostin, YKL-40 and whole blood eosinophils, neutrophils, and IL-17 
Blood collection supplies (vacutainers, alcohol wipes, needles) 
$500 
Blood analysis  
$9,698 
Total Systemic Inflammatory Markers 
$10,198 
 
 
 
Other Supplies: A PFT will be performed on all participants to determine lung function and 
confirm asthma. Each PFT will cost 50$ and will be performed in all participants (n=88). 
Including ultrasound jelly, mouthpieces, and nose clips. 
$4,900 
 
Total Other Supplies 
$4,900 
 
Total Material and Supplies 
$15,098 
 
3. Payment to Study Subjects 
Parking and Honoraria: All research participants will be reimbursed for parking at the 
University of Alberta East Parkade (3 assessments (asthma) X 44 participants + 2 assessments 
(control) X 44 participants= 220 visits). Participants who complete all parts of the study will 
receive a $200 gift card (on average - $25/visit) at their choice. Honoraria for controls will be a 
20$ gift card after completion of the study, and for asthma participants they will be able to keep 
the Fitbit used during the study valued at 125$ (20$ X 44 participants + 125$ X 44 participants). 
Parking ($20/day)  
$4,400 
Honoraria ($200/subject) 
$6,380 
Total Payment to Subjects 
$10,780 
 
4. Publication Cost 
Publications:  
Paper 1  
$1,000 
 
 

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Total Publications 
$1,000 
 
5. Summary 
Salaries and Benefits 
$14,985 
Materials and Supplies 
$15,098 
Payment to Subjects 
$10,780 
Publications 
$1,000 
TOTAL BUDGET  
$41,863 
 

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Appendix 5. Data collection sheet 
 

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