NO Measurements in Screening for Asthma and OSA, in Patients With Severe Snoring
NO Measurements in Screening for Asthma and OSA, in Patients With Severe Snoring
In Denmark an estimated 200.000 patients suffer from obstructive sleep apnoea (OSA). The
 breathing pauses during sleep result in varying degrees of symptoms ranging from none over
 disturbed sleep to severe daytime sleepiness and cognitive deficits such as reduced
 short-term memory and difficulty concentrating. In addition, it increases the risk of
 hypertension, cardiovascular thromboembolic disease and type-2 diabetes as well as causing a
 3-6 times increased risk of being involved in traffic accidents.

 Recent studies suggest that measurement of fractioned exhaled nitrogen oxide (FeNO) from the
 upper airway may be used as marker for airway inflammation. Studies have demonstrated that
 inflammation of the airway is present in OSA.

 In this study the investigators want to see whether FeNO measurements from the upper airway
 can be used to screen severe snorers for OSA.

 OSA is rarely diagnosed in patients with chronic rhinosinusitis (CRSwNP) or asthma. The
 connection between these three inflammatory conditions and the level of FeNO has not
 previously been investigated but might be clarified in our study.

 Patients suffering from severe snoring will be offered inclusion. The patients will undergo
 an ENT examination as well as FeNO testing and testing of lung function. A sleep study will
 be made as well as they will be asked to fill out questionnaires on sleep quality, nasal
 symptoms, lung function and their health in general.
Hypothesis FeNO can be used as screening tool for concurrent OSA and asthma in severe
 snorers.

 Design The study is a prospective, observational multicenter trial. Patients are recruited
 from three different private specialist ENT-clinics where they will be offered inclusion
 according to guidelines. They will not be randomized and there will not be a group of patient
 controls.

 The patients will undergo a full ENT-examination including a fiberoptic examination of both
 nasal cavities and the upper airway. NO-measurements as well as tests of lung function and
 sleep studies (Cardio-Respiratory-Monitoring = CRM) will also be performed. Furthermore,
 patients will be asked to fill out three questionnaires (see below). Patients with severe
 snoring and mild OSA will be offered an evaluation and a DISE (Drug Induced Sedation
 Endoscopy) at the ENT department Rigshospitalet, Gentofte.

 NO-measurements:

 FeNO-measurements will be carried out using a handheld NO-device (NIOX VERO, Aerocrine AB,
 Solna, Sweden). The patients will be asked to blow into a mouthpiece on the device which will
 then calculate the level of FeNO.

 Lung function:

 Tests of lung function will be carried out using EasyOne Pulmonary Function Device where the
 patients will blow into a mouthpiece.

 Sleep studies:

 Sleep studies (Cardio-Respiratory Monitoring = CRM) will be done as overnight home-studies
 using SOMNOtouch RESP that will measure heartrate, oxygen saturation, movement of chest and
 abdomen. All measurements are non-invasive.

 Questionnaires:

 Patients will be asked to fill out questionnaires regarding nasal symptoms (Sino-Nasal
 Outcome Test = SNOT-22) along with questionnaires on sleep quality (Epworth Sleepiness Scale
 = ESS), lung function (ACQ) and general health (The Danish version of Short Form (SF-36)
 Health Survey) developed at RAND as part of the Medical Outcomes Study (MOS). Danish
 validated version by Bjørner JB et al.

 Statistics Data will be processed using IBM SPSS (Chicago, USA). For categorical data
 Pearson's Chi2-test or Fischer's exact tests will be used. Students T-test for normally
 distributed data, while data that are not normally distributed will be analyzed using Mann
 Whitney U-test. Shapiro-Wilks test or graphic plots will be used in the evaluation of data
 distribution.

 Calculation of Power:

 FeNO levels in simple snorers compared to snorers with concurrent asthma or OSA.

 Expected incidence of a severe snorer also having OSA: 25% Expected incidence of OSA in the
 general adult population: 10% Power: 0.8 Significance: 0.5 Sample size: 40 severe snorers

 Risks, disadvantages and advantages:

 There are no known risks associated with the tests of lung function or FeNO measurements. A
 bit of discomfort with blowing forcefully into the mouthpieces during the tests might occur.
 The fiberoptic examination of the upper airway might also result in a bit of discomfort. It
 is expected that paracetamol is sufficient treatment. In the unlikely case that paracetamol
 is not enough patients will be instructed to contact their physician.

 Inclusion in the study will provide the patients with a very thorough examination
 illuminating any concurrent diseases that might explain their symptoms and discomfort. If any
 concurrent disease is found, they will be referred for further specialist treatment.

 Safety precautions The patients will all be examined by specialists in ENT, who are used to
 performing these examinations. All will be thoroughly informed about the tests and the
 motivation for performing them.

 In the unlikely event of pronounced discomfort during a test, it will be stopped.

 Biobank No tissue samples will be collected.

 Data from patient files The investigators have requested access to the patient files in the
 local IT-systems in the three private ENT clinics as well as via Sundhedsplatformen and FMK
 (Fælles Medicin Kort) to verify any medical treatment that might interfere with the study as
 stated in the inclusion and exclusion criteria.

 Prior to inclusion, and consent to participate in the study, data on age, previous illness,
 current medication, and results from the ear-nose-and throat examination will be requested,
 in order to verify that the participants are eligible for inclusion. The information will be
 passed on to the investigators.

 After inclusion and consent is given to participate in the study, data on allergies, weight,
 height, age, gender, concurrent illness, and current medication, will be requested.

 Consent to participate in the study allows the investigators, sponsors, representatives of
 sponsors, as well as the supervisory, direct access to collection of data from patient files,
 including the electronic files, to get information on health-related issues necessary to
 conduct the research project, self-monitoring, and quality-monitoring, as obligated.

 Handling of personal data:

 The rules of Databeskyttelsesordningen / persondataforordning will be followed. Data will be
 stored in accordance with guidelines and only after approval from the local Data Protection
 Agency (Datatilsynet).

 Responsibility for data:

 A: Key investigator Eva Kirkegaard Kiær M.D., ENT-specialist Department of
 otorhinolaryngology, Head and Neck Surgery and Audiology Rigshospitalet, Copenhagen
 University Hospital Blegdamsvej 9, 2100 København Ø

 + 45 35 45 66 35 / 26 70 17 10 eva.kirkegaard.kiaer.01@regionh.dk

 B: Investigator Christian von Buchwald M.D., D.M.Sci Department of otorhinolaryngology, Head
 and Neck Surgery and Audiology Rigshospitalet, Copenhagen University Hospital Blegdamsvej 9,
 2100 København Ø

 + 45 35 45 20 70 christian.von.buchwald@regionh.dk

 C: Investigator Nina Vibeke Backer M.D., D.M.Sci Department of Respiratory Medicine
 Bispebjerg Hospital Ebba Lunds Vej 48, 2400 København NV + 45 38 63 51 22 backer@dadlnet.dk

 D: Investigator Andreas Tomaas Ravn M.D., ENT-specialist Frederiksberg øre-næse-halsklinik
 Falkoner Allé 15, 1. tv., 2000 Frederiksberg + 45 38 87 84 98 atravn@hotmail.com

 E: Investigator Steffen Ørntoft M.D., ENT-specialist Øre Næse Hals Klinikken Gammel Køge
 Landevej 263 1. th., 2650 Hvidovre

 + 45 36 78 88 03 orntoft@dadlnet.dk

 F: Investigator Christian Prætorius and Roland Welinder M.D., ENT-specialists
 Øre-næse-halsklinikken i Hørsholm Kongevejscentret 6, 1. Sal, 2970 Hørsholm

 + 45 45 86 46 00 chr.praetorius@dadlnet.dk

 Key investigator is responsible for the safe storage of data in accordance with the
 guidelines from the local Data Protection Agency (Datatilsynet). Patient data will be stored
 in a locked cabinet in a locked office.

 In accordance with the Danish Law on Health §46, 1+3, the same group of physicians will
 collect data, process data and publish data. Only investigators A, B and C will process data.

 Initiative The initiative for the study is a collaboration between investigator A, B, C and
 D. All the aforementioned investigators have contributed to the outlines of the study.

 Funding The study is partially funded by Fonden for Faglig Udvikling i Speciallægepraksis
 (FAPS) and Øre-næse-halskirurgisk og Audiologisk Klinik, Rigshospitalet.

 All the funding is managed by a research account at Rigshospitalet. The key investigator is
 employed by the Øre-næse-halskirurgisk and Audiologisk Klinik, Rigshospitalet, but does not
 have a financial association to FAPS.

 Remuneration The patients will not be offered remuneration.

 Recruitment Patients will be recruited from three private ENT clinics (investigators D-F).
 Patients will make appointments for consultation in the clinics as usual, based on their
 symptoms, and will be offered inclusion in the study if they fall under the inclusion
 criteria and not the exclusion criteria. All will have the opportunity to consider inclusion
 in the study and will be offered a new consultation if needed.

 Information In accordance with guidelines from the Ethics Committee, participating patients
 will be given both written and oral information about the study, purpose, and consequences.
 Patients will receive the folder "Forsøgspersoners rettigheder i et sundhedsvidenskabeligt
 Forskningsprojekt" published by National Videnskabsetisk Komité (the Central Ethics
 Committee).

 When considering inclusion in the study patients will be offered a new consultation where
 they can bring an assessor. There will be time and opportunity for any questions they might
 have. It will take place in an undisturbed location as to ensure a comfortable environment
 for conversation. Patients will be informed that participation is optional, and their
 treatment will not be affected should they choose not to accept inclusion.

 Patients will be informed of their right to decline information on essential health related
 issues. The informing physician is responsible for ensuring that the information is
 understood. The patient has the right to a minimum of one week to consider inclusion.

 Informed consent On the day of inclusion, or no later than 14 days after, a written consent
 will be obtained. The investigator signs the informed consent stating that the patient has
 received both written and oral information about the project.

 Patients will be informed that they can withdraw their informed consent at any given time,
 and that it will not affect any current or future treatment or consultation.

 Should any essential information about a patient's health appear during the study they will
 be informed accordingly, unless they have clearly stated that they decline such information.

 Publication When the results of the study are available, one of the physicians (A-F) will, as
 far as possible, inform the patients in the study. Information regarding patients is
 protected by "Lov om behandling af personoplysninger" and "Lov om patienters retstilling
 (sundhedsloven afsnit III)".

 Results, both positive, negative or inconclusive, will be published after the completion of
 the study. If publication in a peer review journal is not possible, results will be published
 through other media channels. The study will be registered at www.clinicaltrials.gov

 Ethical considerations The study is approved by the local Ethics Committee as well as the
 Data Protection Agency The purpose of the study is to improve treatment of patients with
 CRSwNP by diagnosing other conditions that might affect their treatment and quality of life
 if undiagnosed. The conditions of interest (OSA and asthma) have symptoms that mimic CRSwNP
 and can therefore be difficult to diagnose if one is not careful to look for them. With this
 study the investigators hope to find a simple test, associated with minimal discomfort, that
 might help screen these patients for OSA and asthma.

 OSA and asthma are conditions associated with severe consequences on both quality of life and
 comorbidity. Hopefully a quick diagnosis will help the patients to relevant treatment thus
 reducing their risk of long-term sequelae.

 Any discomfort during the study seems minimal in contrast to the health benefits it will
 grant patients that are diagnosed with comorbidity as OSA and asthma.

 Insurance Patients are covered by "patienterstatningen" during the study period.
Inclusion Criteria:

 • Severe snorers that seek help based on their personal health and/or social limitations
 due to their snoring.

 Exclusion Criteria:

 -  Patients with known OSA

 -  Patients with nasal polyps

 -  Other inflammatory diseases of the upper airways (i.e. cystic fibrosis, primary
 ciliary dyskinesis) or immune deficiencies, sarcoidosis or systemic vasculitis

 -  Infections in the upper airway during the past two weeks

 -  Smokers

 -  Treatment with antidepressant or sedative drugs

 -  Age below 18

 -  Patients unable to give an informed consent

 -  Patients that do not speak or read Danish