Breathing Counts: Evaluating Adherence in the Presence of Asthma Navigation Support
Phase: NA
Conditions: Asthma
Sponsor: University of Colorado, Denver

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Breathing Counts 
NCT03065205 
Protocol version date 12.18.17 

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1w 
COMIRB Protocol 
COLORADO MULTIPLE INSTITUTIONAL REVIEW BOARD 
CAMPUS BOX F-490    TELEPHONE:  303-724-1055  Fax:  303-724-0990 
 
 
 
Protocol #: 16-1845 
Project Title: Breathing Counts 
 
 
 
Principal Investigator:  Heather Hoch, MD 
Version Date: 12-18-17 
 
 
 
 
 
  
 
I. Hypotheses and Specific Aims:   
 Adherence to asthma medications has been associated with good asthma control in children1, 
however adherence to asthma medications is poor.2 Children who are hospitalized due to their 
asthma are at a significantly high risk of re-hospitalization3, and represent a particularly high risk 
group. Successful control of asthma in a high-risk population requires a network of care providers 
who communicate relevant up-to-date information and support asthma control. Additionally, lay 
health worker interventions have been shown in some cases to decrease missed school days 
and parental work days.4 We propose to evaluate the efficacy of an asthma navigator program in 
a high-risk population of patients at Children’s Hospital Colorado. We will evaluate the ability of 
the program to improve health outcomes of children who have asthma and who are at high-risk 
of re-hospitalization.  The project will also evaluate the ability of the navigator program to 
increase the number of stakeholder communications amongst school nurses, program 
navigators, physicians, caregivers and children. 
Specific Aim 1: Evaluate whether or not the addition of an asthma navigator to the current clinical 
standard of care will lead to sustainably increased levels of adherence compared to historical 
rates.     
Hypothesis: By providing up to date adherence rates to the patient’s medical care team 
and by addressing patient identified barriers, we hypothesize that the addition of an asthma 
navigator to the standard of care at Children’s Hospital will increase asthma medication 
adherence rates, and that these adherences rates will be sustained over the 3-6 month 
monitoring period.    
Specific Aim 2 Evaluate whether or not the addition of an asthma navigator results in increased 
levels of communication between PCPs, specialty providers and school nurses. 
Hypothesis: The addition of an asthma navigator will result in increased emails and general 
communication between various providers in a patient’s care team. 
Specific Aim 3 Evaluate whether or not other asthma related outcomes (measures of asthma 
control, asthma related quality of life, presence of a school asthma action plan, among others) are 
altered with the addition of an asthma navigator to a patient’s care team. 
Hypothesis: The addition of an asthma navigator will improve other markers of asthma 
control and quality of life. We anticipate an increase in asthma control and increase in the 
number of patients with a school asthma action plan. 
 
II. Background and Significance:  
Adherence to asthma medications is poor 
Adherence to asthma medications is poor, especially in high-risk populations,5 and even with 
monitoring studies show adherence worsens over time.6 The large Childhood Asthma Management 
Program study found that 75% of children studied had adherence levels of less than 80% when 
measured objectively.7 In fact, one review of previous attempts to measure adherence to asthma 
medications utilizing electronic monitoring devices showed adherence rates between 28-73%, with 
only one study showing an adherence rate above 90%.8 
Asthma morbidity is a significant public health problem.   

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Over eight percent of children in the US carried a diagnosis of asthma in 2013, and 58% of those 
children had an asthma exacerbation in that year.9 Asthma exacerbations/hospitalizations remain a 
significant source of healthcare expenditures10 
Inhaled corticosteroids have been shown to significantly improve asthma control 
The use of low-dose ICS in asthmatic children and adults has been shown to significantly decrease 
the rate of asthma-related hospitalization11 and asthma related death.12 Additionally, chronic use of 
inhaled corticosteroids has been shown to improve asthma control.13  
Adherence has been correlated with some improved asthma outcomes.  
Previous evaluations of adherence using electronic monitoring devices have shown lower 
adherence rates to be correlated with higher levels of healthcare utilization,14 and worsened levels 
of asthma control15,16 A small study of Australian children showed a trend toward improvements in 
lung function with greater adherence, however this failed to reach statistical significance.17 The 
correlation of adherence to other asthma outcomes including exacerbations and various markers of 
lung function/inflammation in high risk children has not yet been studied.   
Non-adherence disproportionately affects a high-risk population of children with asthma.  
High-risk children are disproportionately of color, have low household levels of education and 
income, attend poorer performing schools, come from lower socio-economic background.18 
Poorly controlled asthma contributes to poor school performance by disrupting sleep and causing 
missed days of school19,20, and associations between poor asthma control and missed school are 
higher among minority children.21 Researchers have suggested possible determinants of non-
adherence including concerns about medication adverse effects, belief that asthma is not a serious 
problem, belief that medications are not helping, and preference for a non-pharmacological 
approach, among others.22 In order to address both the persistent high levels of morbidity 
associated with asthma and increasing disparities, new approaches to asthma management are 
needed to more effectively deliver evidence-based preventive treatments and identify children who 
need a more intensive, stepped up treatment plan.  While some interventions based in schools, in 
the home, or in the community have shown promise,23-25 important limitations have included lack of 
coordination with community health care providers (HCPs), lack of involvement of schools and the 
community, inability to monitor medication adherence and lack of sustainability. In short, we aim to 
reduce health disparities with this program by targeting the highest risk asthma patients, those 
admitted to the hospital inpatient or emergency department with an asthma exacerbation, which 
tend to be disproportionately minority patients, and utilize new and innovative technology to 
improve care for these patients.   
 
 
III. Preliminary Studies/Progress Report:   
We have been conducting a pilot study evaluating the use of electronic adherence 
monitoring devices in the pediatric asthma population.  We have collected preliminary 
data on the usability of these devices in our population of children aged 6-17.  
Preliminary evaluation of this data has shown that the devices are largely well 
tolerated, and data from the devices is accessed often by providers.  Most patients 
feel comfortable utilizing smartphone applications, and the majority of patients found 
the devices easy to use.  
 
IV. Research Methods 
 
A. Outcome Measure(s):   
 
A table of outcomes to be collected during the study time period is give below (table 1).  A detailed 
description of the outcome follows.  
 
 
 
Outcome Measure 
Visit 1 
(admission 
visit) 
Visit 2 (2 
months) 
Visit 3 (4 
months or end 
of study) 
Visit 
4 (6 months 
or end of 

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study) 
 
 
 
 
 
 
 
Aim 
1 
Adherence  (continually 
monitored during trial) 
 
X 
X 
X 
Aim 
2 
Communication among 
providers 
X 
 
 
X 
Aim 
3 
Asthma Related Health 
outcomes 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
a. Adherence- measured on adherence monitoring devices. The rate of daily 
prescribed controller medication use will be monitored.  For example, if an 
individual is prescribed two doses per day and the monitoring device records one 
doses, then the daily adherence measure will be 1/2 or 50%.  The outcome 
measure will be continuously gathered via the Propeller Health monitoring device 
® (Madison, WI).  Rate of monthly adherence will be calculated between study 
visits,  
b. Communication between providers.  Communication between providers will be 
measured in a number of ways.  Providers include nurses, parents, physicians and 
patients.  In order to measure any change in communication the following 
communication metrics will be monitored. 
i. Number of emails sent between providers will be assessed if email is used 
as the primary means of communication. 
ii. A subset of provider teams will possibly be enrolled in asynchronous 
communication monitoring.  This is a method of HIPAA compliant 
messaging, which involves providers utilizing an application or website, 
and communicating securely within that platform.  We plan to utilize the 
Stich platform, which is marketed as HIPAA compliant 
(https://www.teamstitch.com).  We are currently on a waiting list to 
possibly test the technology.   
iii. Providers will be surveyed before and after the intervention to determine if 
they felt that the navigators adequately improved communication regarding 
specific patient related issues.   
c. Other asthma related outcomes including asthma control test, symptom 
assessments, asthma related readmissions or revisits, missed school days, and 
provider satisfaction. 
i. Asthma Control Test, a self (or in the case of this study, phone 
administered)-administered questionnaire with 5 questions which 
summarizes asthma control, will be used to record asthma control in 
children 12 or older.   
ii. Childhood Asthma Control Test (or in the case of this study, phone 
administered), a parent and child administered questionnaire, will be used 
to record asthma control for children 6-11 years of age. 
iii. Pediatric Inhaler Adherence Questionnaire, a self (or in the case of this 
study, phone administered) survey of barriers to medication adherence 
iv. Parent attitudes towards medications and barriers to adherence.   
v. Changes in adherence barriers and behaviors to improve adherence over 
time 
vi. The number of asthma related readmissions or revisits between study 
visits will be self-reported.  

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vii. The number of missed school days between visits will be self-reported.  
viii. Provider satisfaction will be recorded using the pre-post surveys 
 
B. Description of Population to be Enrolled:   
a. Children admitted to Children’s Hospital Colorado inpatient or emergency 
department with a primary diagnosis of asthma exacerbation.   
i. Inclusion criteria-patients 
1. Age 6-17 years 
2. On a controller medication at baseline 
ii. Inclusion criteria-providers 
1. Aged 18-70 
2. Caring for a patient that is enrolled in the study 
iii. Exclusion criteria 
1. Primary language other than English or Spanish (smartphone 
application only available in these languages) 
2. Homeschooled or not in school 
3. Significant developmental delay, cystic fibrosis, interstitial lung 
disease, tracheostomy/ventilator dependence 
4. Following up with a pulmonary or allergy provider outside of the 
CHCO system 
 
C. Study Design and Research Methods 
 
The proposed study is a single center trial at Children’s Hospital of Colorado, designed to evaluate 
the effects of a navigator program on medication adherence, provider communication and other 
asthma related health outcomes.  Participants will be recruited from the population of patients 
between the age of 6 and 17 years admitted to Children’s Hospital Colorado inpatient or 
emergency department with a primary diagnosis of asthma exacerbation.  Investigators plan on a 
one-year enrollment period and will follow each study participant for 3-6 months.  
 
Recruitment 
 
Upon admission hospital staff will identify potential participants based on the admission medical 
record.  Patients will be approached by research staff and asked if they would like to participant in 
the study.  A member of the research team (principally, the research coordinator) will do the 
recruiting.  The research coordinator will explain the study and enroll subjects. Estimated duration 
is 45-60 minutes depending upon the patient.  
 
Consent/Assent 
 
We will obtain a signed parental permission form and an age-appropriate assent form for 
participants younger than 18 years.  Consent will be obtained by a member of the research team 
(principally, the research coordinator or a research assistant). It will be made clear to patients that 
the research team is not part of the treatment team. 
 
  
Study Design 
 
 
We plan to enroll a total of 100 patients. and up to 400 providers. Patients enrolled will be provided 
and trained on using the adherence monitoring prior to discharge (sensors will be placed on 
discharge controller and quick-relief medication).  Participants will also be enrolled in the 
smartphone application that will give them feedback about their medication usage.  Once enrolled 
in the application, patients will receive push notification reminders to use their medications, as well 
as be able to access their adherence information in real time.  Caretakers will also be given the 

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option to have access to their child’s adherence information.  The smartphone application also has 
portions dedicated to education about asthma triggers. Patients will be set up with a pulmonary or 
allergy follow up within 2-4 weeks of discharge.   Patient’s pulmonary or allergy providers will also 
be enrolled in the propeller health system, with access to the propeller health dashboard.  Once 
providers receive access, they will be able to log-in and view all of their patients in list format.  They 
will be able to see up to the minute data on patient adherence at any time that they choose to log-in 
to the dashboard.  Providers will also receive email notifications if their patient has not used their 
controller medications for 7 days, or if their patient has had a significant increase in quick-relief 
medication use, indicating a worsening of asthma status (see figure 1 below).  Patients will be 
monitored for a total of 3-6 months.  The asthma navigator will contact the families at 2, 4 and 6 
months post-enrollment, and discuss the patient’s recorded adherence with the families. If a patient 
is enrolled for 4-5 months, we will discuss adherence at 2 and 4/5 months. If  a patient is only 
enrolled for 3 months, we will discuss adherence at 2 and 3 months.  Additionally, they will discuss 
any barriers to adherence that the family may be experiencing, and make referrals to social work 
as necessary, as well as attempt to brainstorm ways to improve adherence with the families.  
Additionally, the asthma navigator will collect each patients’ adherence data and create an 
adherence report, which will be distributed on a monthly basis to the patient’s primary care 
provider, pulmonary/allergy provider, and school nurse via email. The asthma navigator will be 
monitoring communications between the providers and marking the numbers of communications. 
 
At the time of enrollment, patients will be asked for permission to contact the child’s primary care 
provider and school nurse.  If these providers agree to participate in the study, surveys will be sent 
to all providers of patients (PCPs, school nurses and specialists) to determine if they found the 
navigator to be helpful, and to see if communication increased due to the intervention. Additionally, 
the research coordinator will be monitoring the provider portal to ensure that patients’ devices are 
regularly syncing with their phone’s Bluetooth, and contact any patients whose devices are not 
syncing normally. At the study’s conclusion, we will plan to have the families return the devices to 
the research coordinator via US mail. After the conclusion of the study, families will be contacted by 
the research coordinator to ask if they would be willing to evaluate the navigator via the PSN-I 
navigator assessment tool.  The navigator assessment tool will be used to evaluate utility of the 
navigator themselves.  This is a tool that has been utilized previously in this context to evaluate 
efficacy of navigator programs.  This will only be evaluated at the end of the study.  There will be 
no reimbursement for time for this last survey.      
 
If a patient is having difficulties with syncing their sensors to their phone, we will provide them 
with a hub to collect the sensor data.   
 
 
 
  
D. Description, Risks and Justification of Procedures and Data Collection Tools: 
There will be no medical procedures done during this study.  The data collection will occur 
via surveys, and data collected from the adherence devices.  Risks of data collection 
include accidental disclosure of information, though steps will be taken to prevent this.  
Also, there is a GPS capability of the devices, so there is a risk of disclosure of patient’s 
location patterns.   
 
 
    
E. Potential Scientific Problems:   
We are aware that we are underpowered to fully evaluate some of the outcomes that we 
are interested in obtaining.  Additionally, we are limited to single group analysis by request 
of the funding agency (rather than also having a control group), so we are limited in our 
ability to make full comparisons.  However we would like to undertake this study as a pilot 
evaluation for the use of the asthma navigator in this population, utilizing adherence 
monitoring technology to better understand the influence of these evaluations.     

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F.   Data Analysis Plan:   
 
Analysis plan 
 
Demographic information including age, sex, race, and other baseline clinical 
information upon recruitment including duration of asthma, C-ACT score, ACT score, 
asthma symptoms, lung function, prescribed medication, and asthma related health 
care use in the previous year will be obtained at enrollment.  The distributions of 
outcomes will be examined for normality using the Anderson-Darling Test.  
Dependent upon the distribution we will use the Wilcoxon rank-sum test, Mann-
Whitney U test or paired T-test to test for significant changes in outcomes during the 
study period. Longitudinal patterns of adherence will be examined graphically.   
 
Monthly rates of adherence, asthma symptoms, asthma control scores and monthly 
missed number of school days and number of hospitalizations will be calculated by 
study arm.  Survey information from patients, caregivers, physicians and navigators 
on the navigator intervention will be reviewed by study staff and summarized 
qualitatively. Number of rehospitalizations will be obtained via chart review at 1 
month, 6 months and 12 months post hospitalization.   
 
The cost-effectiveness of the navigator intervention will be summarized based on 
medical resource utilization (direct) and loss of productivity (indirect). Medical 
resources utilization will include medical care resource utilization, asthma medication 
variables, navigator time and salary, while loss of productivity will be measured using 
the number of hours caretaker missed work due to participant’s asthma, number of 
hours dependent participant missed school due to his/her asthma, and number of 
hours independent participant missed work due to his/her asthma. Unit costs will be 
applied to healthcare resources and loss of productivity and summed to obtain total 
costs for each subject.  Average costs for the study group will be presented. 
 
Power and Sample Size 
 
The study is limited by time frame and funding for a one year recruitment period.  The 
primary goal of the study is to provide preliminary information on the effect of a 
navigator program on the patient and caregiver response to asthma disease control.  
As a pilot and feasibility study, investigators have chosen to enroll a total of 100 
patients and up to 400 providers.  Through past clinical experience, we know that 
some months of the year are higher risk for asthma exacerbations, so we expect to 
screen more patients during the fall and winter than summer or spring.  Considering 
the variable clinical case load Investigators plan on enrolling an average of 10 
participants per month. Anticipating an enrollment rate of approximately 20% (in 
2015, there were >600 asthma related admissions at Children’s Hospital Colorado), 
investigators state they should be able to enroll up to 100 patients within one year.  
We plan to enroll up to 4 providers per patient with a simple pre-post survey as well. 
 
The primary hypothesis of interest is to test whether change in adherence rates are 
different from zero.  The smallest detectible difference was based on a paired sample 
t-test between pre and post adherence scores with a Type I error rate of 0.05 and 
90% power.  Based on previous studies8, investigators assumed a mean adherence 
rate of 50% with a standard deviation of 22%.   

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Table X lists the smallest detectable 
difference (Δ) for by sample size.  For 
the primary aim investigators will be 
able to detect a change of 8% or more 
in percent adherence during the study 
period with the available 100 patients. 
 
   
 
 
F. Summarize Knowledge to be Gained:   
a. Utility of an asthma navigator in addition to electronic 
adherence monitoring in improving adherence to asthma 
medications 
b. Utility of an asthma navigator in improving communication 
amongst all of a patient’s medical providers 
c. Utility of an asthma navigator in improving other asthma control 
related outcomes.  
Table X: 
 
N 
Δ 
100 
8% 
65 
10% 
30 
15% 

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Figure 1 
 
 H. References: 
1. 
Klok T, Kaptein AA, Duiverman EJ, Brand PL. It's the adherence, stupid (that determines 
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Engelkes M, Janssens HM, de Jongste JC, Sturkenboom MC, Verhamme KM. Prescription 
patterns, adherence and characteristics of non-adherence in children with asthma in 
primary care. Pediatric allergy and immunology : official publication of the European 
Society of Pediatric Allergy and Immunology. 2016;27(2):201-208. 
Asthma Control Classification 
 
Control is computed based on taking the entry with the worst outcome in the following 
age­based tables: 
 
Asthma Control Classification (Age 5­10) 
 
Asthma Control Classification (Age 12 or older and adults) 
 

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