Adherence in Global Airways - Difference Between Structured and Systematic Nursing Supervison vs Usual Care
Phase: NA
Conditions: Chronic Rhinosinusitis Without Nasal Polyps, Asthma, Chronic Rhinosinusitis With Nasal Polyps, Chronic Rhinosinusitis (Diagnosis)
Sponsor: Christiane Haase

06.05.2022 
 
 
 
NCTXXXXXXXX 
 
Adherence in Global Airways - Difference Between Structured and Systematic  
Nursing Supervison vs Usual Care.  

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Abbreviations 
ACT - Asthma Control Test 
ACQ-7 Asthma Control Questionnaire 
Adherence - Patients adherence to their non pharmacological/pharmacological treatment 
CRS -Chronic Rhinosi Chronic sinusitis 
CRSsNP - Chronic sinusitis with no nasal polyps 
CRSwNP Chronic sinusitis with nasal polyps 
ESS - EPWORTH SLEEPINESS SCALE 
Global Airways - Lower and upper respiratory diseases (asthma, rhinitis and CRS/CRSwNP/CRSsNP) 
HADS - Hospital Anxiety and Depression Scale 
MARS-5 - Medication adherence report scale 
MARS-5-L - Medication adherence report scale - lung 
MARS-5-N - Medication adherence report scale - nose 
miniAQLQ - Mini asthma quality of life questionnaire 
miniRQLQ - Mini Rhino conjunctivitis Quality of Life Questionnaire 
RCT - Randomised Controlled Trial 
SNOT-22 - The Sino-Nasal Outcome Test 22 
STARR-15 - Standard test for asthma, rhinitis and chronic rhinosinusitis (15 questions) 
ENT - Department of Ear, Nose and Throat Surgery and Audiology, RigsHospitalet 
 
Introduction 
There is a strong case for treating diseases of both the upper and lower airways (global airways) simultane- 
ously, because they share the same inflammatory mechanisms (1,2). About 9% have chronic sinusitis (CRS) 
and 4% of the Danish population are diagnosed with (CRS) with nasal polyps (CRSwNP) and 7-10% have 
asthma. CRS has a multifactorial background, with CRSwNP characterized by Type 2 inflammation, and ap- 
proximately 50% with Type 2 CRSwNP also have co-morbid asthma (3). Well-treated CRS has an impact on 
asthma control, and well-treated asthma has an impact on CRS. 
The above can be strongly supported by daily clinical practice, where these patients experience high levels of 
morbidity, which often significantly affect their daily lives and thereby also result in a markedly reduced 
quality of life. Several studies show that patients with asthma have low adherence (4,5), but only a few if any 
of studies are available on adherence in CRS. Patients rely on seeing different specialists (otolaryngologist 
and pulmonologist) to optimize their adherence in the upper or lower airways. This provides an opportunity 

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to investigate patients' adherence with diseases of the global airways, and analyse whether patients' adher- 
ence with diseases of the global airways can be improved and whether this will contribute to increased dis- 
ease control and significantly improved quality of life. 
Purpose 
To investigate the effect of systematic and structured nursing guidance in patients with global airways dis- 
ease, CRSwNP and asthma primarily on adherence (measured on MARS-5- L/N), where the maximum score 
is 50 at 100% adherence for both diseases. As well as whether there is a change at the minimum in adherence 
in patients who receive systematic and structured guidance on disease and treatment compared to usual care 
which does not include structured guidance. 
Hypothesis and research questions 
Patients with respiratory diseases can improve their adherence to their non-medical and the medical treat- 
ment for CRSwNP/CRS and asthma by systematic and structured nursing guidance compared to patients 
who did not receive the above guidance. 
In a randomized study, we will investigate whether the level of adherence measured by the questionnaire 
MARS-5-N and MARS-5- L in patients with CRSwNP/CRS and asthma can be improved by 5 points after 
systematic and structured nursing guidance at baseline visit and controlled after four months - compared with 
those patients who have not received the above guidance. 
Outcomes 
The primary outcome is to investigate whether the adherence rate measured by the MARS-5-N/L ques- 
tionnaire in patients with CRSwNP and asthma can be improved by 4 points after systematic and struc- 
tured nursing guidance at the initial visit and controlled after four months - compared with those patients 
who have not received the above guidance. 
Secondary outcomes 
- To demonstrate whether improved adherence can improve their sleep measured on a Epworth Sleepi- 
ness Scale - messured during a 4 month follow-up visits. 
- To demonstrate whether improved adherence can improve their SNOT22 score by 9 points or more 
messured at a 4 month follow-up visits. 
- To demonstrate whether improved adherence can improve their asthma control as measured by the 
ACQ messured at a 4 month follow-up visits. 
- To demonstrate whether improved adherence can improve their asthma control as measured by ACT - 
measured at a 4 months follow-up visit. 
- To demonstrate whether improved adherence can improve their quality of life as measured by the mini 
AQLQ messured at a 4 months follow-up visit. 

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- To demonstrate whether improved adherence can improve their anxiety/depression as measured by 
HADS - messured at a 4 months follow-up visit. 
- To demonstrate whether satisfactory adherence (i.e. 80%) can improve their nasal symptoms measured 
via SNOT22 and STARR-15 - messaured at 4 a months follow-up. 
- To demonstrate whether satisfactory adherence (i.e. 80%) on lung measured via MARS-5-L and poor 
adherence on nose measured via MARS-5-N improve their respiratory symptoms measured ACQ or 
ACT - messsured at a 4 months follow-up. 
- Demonstrate differences in patients with three conditions (asthma, CRS and allergic rhinitis) measured 
via STARR-15 meassured at a 4 months follow-up visit. 
 
 
Background 
CRS is a condition of chronic inflammation of the nose and sinuses. CRS can appear in the nasal polyps 
(CRSwNP) and without polyps (CRSsNP)(2,3). 9% of the Danish population is affected by CRS, and ap- 
proximately 4% are estimated to be diagnosed with CRSwNP (4). The diagnosis is based on the patient's 
symptoms and objective signs of inflammation in the nose and sinuses. Symptoms include nasal congestion 
or nasal secretion that runs forward or backward, decreased air passage, decreased sense of smell, pain/pres- 
sure around the nose, forehead or eyes. For the diagnosis to take place, the above symptoms must have been 
present for more than 12 weeks. To diagnose CRS, there must be secretions or reduced air passage through 
the nose (6,7). Approximately 40% of CRS patients in primary care have asthma, whereas 65% referred to 
hospital have asthma (8). 
CRSwNP that is not satisfactorily controlled has a significant impact on quality of life (9,10). It is often char- 
acterized by type 2 inflammation, i.e. increased numbers of eosinophils in the mucosa of the sinuses and na- 
sal polyps - as well as comorbidities e.g. asthma, ASA/NSAID intolerance (N-ERD) and allergies (3). 
CRSwNP can be treated both surgically and medically. Basic medical treatment of CRS includes daily saline 
irrigation and application of nasal steroid. In the case of nasal polyps, systemic steroid (tbl. prednisolone/inj. 
betamethasone) may be added as a course, and never as a fixed treatment (3,6). Some patients receive 1, 2 or 
3 courses annually for several years, which is accompanied by many systemic side effects (1,2,11). If medi- 
cal treatment is not optimal, patients may be offered surgical treatment -endoscopic sinus surgery (ESS)(2,3). 
The goal is the removal of polyps in the nose and sinuses, to create better air passage. 
Comorbidity 
In patients with CRS, attention should also be paid to comorbidity due to the interplay between the upper and 
lower airways. Patients with uncontrolled CRSwNP often suffer from a high burden of disease (9). Asthma 
and CRSwNP often interact negatively. Therefore, patients should also be evaluated for asthma. Patients 
with CRSwNP and type-2 inflammation (high eosinophil cell count in the blood or mucosa of the nose) are 

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more likely to have recurrence of CRSwNP after surgery than patients with low eosinophil cell count (3). 
Patients with asthma may also experience more rapid recurrence of their polyps after surgery than patients 
who do not have asthma. 
Asthma 
Asthma is a chronic inflammatory respiratory disease. It is characterized by chronic airway inflammation, 
airway hyperactivity and variable airway obstruction (12). It is estimated that over 300 million people world- 
wide suffer from asthma, of wichic most are born and raised in the Western world, which has a major impact 
on the economy (5). Symptoms of asthma include coughing, wheezing, shortness of breath, chest tightness, 
etc., and can vary in intensity. The diagnosis is made on the basis of disease history and objective findings, 
e.g. spirometry, FeNO measurement, provocation tests, and peak flow test (12). 
 
Adherence 
The term adherence describes the patient's compliance with the treatment strategy developed in consultation 
with a practitioner. The patient is considered an active participant in his or her treatment. Adherence can be 
measured for both pharmacological and non-pharmacological treatment. The WHO classifies measures of 
adherence as subjective and objective (13,14). Objective measures include measures such as pill counts, elec- 
tronic monitoring (common medical card) or biochemical measures (e.g. blood tests) (13). Subjective meas- 
urements include those that require assessment by, for example, the doctor, nurse or patient. Self-reporting 
by the patient or assessment by the healthcare professionals are the most common methods used to assess 
patient adherence. MARS-5 is a subjective tool that can be used to measure patient adherence - developed by 
Professor Rob Horne (15,16). The MARS-5 is a generic tool. It has been validated in many different clinical 
settings, e.g. in patients with asthma (17). The MARS-5 consists of five questions describing patient adher- 
ence to their medical treatment. Question 1) "I forget to take them", question 2) "I change the dose", question 
3) "I stop taking them for a while", question 4) "I decide to skip a dose" and question 5) " I take less than in- 
structed". Patients are asked to rate their adherence to their medication on a 5-point scale ranging from "al- 
ways" to "never" (1-5 points). The total score on the scale goes from 5 (lowest compliance) to 25 points 
(macsi-mal compliance). 
Poor adherence is particularly seen in long-term treatment among chronic patients, underlining the im- 
portance of focusing on sustained adherence in these patients (18). Some patients stop their treatment when 
they have symptoms under control, after which an exacerbation occurs. They resume their treatment with the 
feeling that "it is not helping" because they get worse (19). The WHO estimates that only 50% of patients 
receiving long-term pharmacological treatment for their chronic diseases are adherent to their treatment 
(19,20). Adherence in asthma and COPD has been shown to vary between 22%-78% (5,19). Patients with 
asthma receive information, guidance, and training related to their disease in the context of "usual care" in 
many places. Patients' adherence to pharmacological treatment depends on their age, their level of education, 
their knowledge of asthma, how often they have to take medication, whether the medication is easy to take, 

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Inclusion criteria 
Exclusion criteria 
Adherence to MARS- 5 L/N ≤35 
Adherence to MARS-5- L/N >35 
at first visit 
points at first visit 
Diagnosed with asthma (with and 
Do not have smartphone 
without allergic rhinitis) at initial 
visit 
Able to use smartphone 
Does not read or speak English 
ACQ ≥1.2 or ACT≤15 (partially 
Other illness requiring regular 
uncontrolled asthma) 
medication 
Be over 18 years of age 
Pregnancy and pregnancy that 
started during the study time pe- 
riod 
SNOT-22 score ≥35 
Servere psychological comorbidi- 
ties 
Diagnosed with CRSwNP 
and how their communication is with the practitioner (19,20). Adherence to inhaled medications is lower 
than to oral tablets or injectable medications. The more complex and the more times the patient has to re- 
member to take the medication, the harder it is to establish optimal adherence (19,20). 
CRSwNP a chronic disease like asthma, where low adherence is often seen in mild to moderate cases com- 
pared to severe cases of CRSwNP (21). However, the clinical perception is that not all patients take all their 
daily doses, but few scientific studies have focused on this. The difficulty in treating CRS is that the patient 
must apply nasal steroid 1-2 times daily as well as it must be combined with nasal saline irrigation at least 
once daily. Decreased adherence is led by poor disease control. It is therefore important to support and 
strengthen patient adherence to CRS and asthma in order to achieve good disease control (21). 
Population and recruitment 
The study population consists of patients referred to the Respiratory Clinic in the Department of Ear, Nose 
and Throat Surgery and Audiology, Rigshospitalet. Patients are recruited by initial visits to the Respiratory 
Clinic, where they receive oral and written information about the project. If patients wish to participate, they 
must complete a written consent form for participation in the project. In order to be included in the study, the 
following inclusion and exclusion criteria must be met: 
 

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Material and method 
The study is a randomized trial with a control group and an intervention group. Patients will be random- 
ized via Research Electronic Data Capture (Redcap), a secure web application for building and managing 
databases and online questionnaires. The system was developed at Vanderbilt University, which released 
the first version in 2008 (22). Patients will be randomized to the control or intervention group. Random- 
ization will be stratified by gender. Patients in the intervention group will receive systematic and struc- 
tured nursing guidance regarding their adherence, which includes proper use of nasal irrigation once or 
twice daily, nasal steroid/drops, use of inhaled medications, follow-up of smoking status. The interven- 
tion group will receive guidance videos which have been prepared prior to the study and will be standard 
for the intervention group. Guidance videos will cover the correct use of nasal irrigation, inhalation 
steroid, and nasal steroid/drops. The control group and intervention group will receive twice a week text 
message reminders to take their medications and to rinse their nose. 
Their adherence will be measured via MARS-5-N and MARS-5-L f. Total MARS-5-N/L will be meas- 
ured at their initial visit and four months after teaching or usual care. The same form will be given at 
both visits. Patients in the control group will not receive systematic and structured nursing care regarding 
their adherence, but their adherence will be measured via MARS-5-N and MARS-5-L max score is 50 
when measuring a adherence in global airways. In a pilot study, mean (SD) 20.4 (6.28) is found for 
MARS-5-L, and for MARS-5-N mean 20.7 (5.57) is found. 41 points correspond to 80% of total of both 
MARS-5-L and MARS- 5-N. A satisfactory adherence should be 80%. In another pilot study, patients 
were measured twice with at least one month in between. Here, the mean of the inter-individual differ- 
ence at MARS-5-L/N first and second time is equal to 5.34(2.62). These two pilot studies will be used 
for the final power calculation. 
 
Statistics data analysis and power calculation 
The statistical analysis of data is performed using IBM SPSS Statistics. Results will be presented as 
mean, SD, range and 95% CI. The parametric data will be compared using paired and unpaired tests, 
and non-parametric data using Wilcoxon Signed-Ranks Test and Mann-Whitney Test, respectively. Cat- 
egorical variables are tested by chi-square test. A P-value <0.025 is considered significant for a pooled 
MARS-5-N and MARS-5-L For a pooled MARS5-L/N questionnaire, the total score would be 25x2= a 
total of 50 points theoretically. A safe difference is calculated from the intraindividual difference de- 
tected in the pilot study (mean 5.34 (2.62)) , but based on the pilot study an SD and mean are calculated 
on the difference between MARS-5-L/N, which corresponds to an SD 5.34 and mean 2.62. With a 
MIREDIF of 5 and the largest SD of 6.28 by single measurement with a p-value of 0.025% (0.05/2) 
because there are two schedules and a power 80%, this would require 36 patients in each group including 
a dropout of 20%. 

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In addition, ensuring that MARS-5-N/L are both above 80% (the standard requirements for good adher- 
ence); and hoping for 100% adherence in the intervention group, versus 80% in the control group, this 
would require 39 in each group. - And including the 20% dropout rate, the total population would be 47 
in each group. 
 
Project participants 
Jamina Ninel Hermann, nurse, Department of Otolaryngology and Audiology 
Ditte Gertz Mogensen, clinical nurse specialist and ph. Student, Department of Ear, Nose and Throat Surgery 
and Audiology 
Kasper Aanæs, Senior Physician, Department of Ear, Nose and Throat Surgery and Audiology 
Vibeke Backer, Professor, MD, Department of Ear, Nose and Throat Surgery and Audiology 
Risks and side effects 
There are no serious side effects associated with participation in the trial. There may be a risk that patients in 
the control group of the study may have a worse prognosis/prognosis than patients achieving good adherence 
(80%) in the intervention group. To reduce this risk, patients in the control group are offered the same guid- 
ance as those in the intervention group at the end of the trial. 
Information from patient records 
No personal data will be collected from patient records. Data included in the study are from patient question- 
naires and from results of clinical objective tests. 
Processing of personal data 
The project is carried out in compliance with the Data Protection Regulation and the Data Protection Act. 
 
Economy 
The patients are part of clinical outpatient treatment, at the Department of Ear Nose and Throat Surgery and 
Audiology, Rigshospitalet, and there is no increased financial consumption in connection with this, fund 
funding has been sought for additional work for the nurse. 
Conflicts of interest 
There are no financial conflicts of interest to report related to this project. 
 
Publication of results 
It will be made public in various journals and congresses. 
 
Scientific ethical considerations 
The study will be conducted according to the Helsinki Declaration. The project has been notified to the re- 
search directory of the Capital Region, Pactius, as the Capital Region is the data controller. 

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Referencer 
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0303-6 
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Reddel HK, Bacharier LB, Bateman ED, Boulet L-P, Brightling C, Brusselle G, et al. GINA-Main- 
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Informed consent for participation in a health science research project 
 
Research project title: Adherence in global airways – difference between structured and sys- 
tematic nursing supervison vs usual care - a randomized controlled trial 
 
Trial participant declaration of consent: 
I have received written and oral information and I know enough about the purpose, the method, the ad- 
vantages, and the disadvantages of the trial to give my consent to participate in the trial. 
 
I know that it is voluntary to participate and that I can withdraw my consent at any time without losing 
my present and future rights to receive treatment. 
 
I give my consent to participate in the research project and have received a copy of the declaration of 
consent, as well as a copy of the written information about the project. 
 
Name of the trial participant:  
 
 
Date:  
 
Signature:  
 
 
 
You will be informed if significant new information regarding your health is disclosed during the re- 
search project. If you request to not be informed about significant new information regarding your 
health that is being disclosed during the research project, please tick here:  
(x) 
 
Would you like to be informed about the results of the research project and any consequences it might 
have for you? 
Yes  
(x) No  
(x) 
 
Would you like to receive text messages from Department of Otorhinolaryngology, Head and Neck Sur- 
gery & Audiology with reminders to take your medication and fill out and complete the diary? 
 
Yes  
(x) No  
(x) 
 
 
Declaration from the person providing information: 
I declare that the trial participant has received oral and written information about the trial. 
I believe that sufficient information has been provided in order to make a decision regarding participa- 
tion in this trial. 
 
Name of the person providing information:  
 
 
Date:  
 
Signature:  
 

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