Nasal and Oronasal Mask in Severe OSA Patients With Nasal Free Airflow of Obstruction

Nasal and Oronasal Mask During CPAP Titration on CPAP Level, Apnoea-hypopnoea Index, Airway Defense Biomarkers and Systemic Expression of mi RNA in Patients With Severe Obstructive Sleep Apnea and no History of Nasal Obstruction

The obstructive sleep apnea (OSA) affects between 10% to 25% of the adults. Continuous positive airway pressure (CPAP) is the first choice of treatment in severe OSA. However, the adherence to CPAP varies, and the interface between patient and the CPAP may interfere with adherence, comfort and efficiency as well as in sleep variables. Objectives: (1) to determine if self-reported airflow route (nasal or oronasal airflow) is the same as the route determined in a laboratory analysis in controls (healthy subjects) and severe OSA patients with nasal free airflow of obstruction during asleep and awake, (2) to compare the effects of nasal and oronasal CPAP titration (randomized order of masks, 14 days apart) on apnoea-hypopnoea index, CPAP level, PSG variables - including analysis for body positioning, the airway defense mechanisms (nasal mucociliary clearance, mucus properties, citology and inflammation in nasal lavage fluid) and systemic effects (serum miRNA expression and cytokines), (3) CPAP adherence after 1 month and 12 months.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea of Newborn
• Intervention / Treatment: Device: Nasal CPAP; Device: Oronasal CPAP

Detailed Description

After agreement with the written informed consent, 30 volunteers (10 healthy volunteers and 20 patients with severe OSA), male and female, aged > 21 years were recruited in the Sleep Laboratory of Hospital das Clínicas da Faculdade de Medicina (FMUSP). The volunteers were evaluated at the Sleep Laboratory (Incor) in two phases. First Phase: volunteers were assessed for breathing route awake and asleep (including respiratory events in OSA patients) and were indicated as nasal breathing and oronasal breathing. Second phase for OSA patients: two manual full-night CPAP titration with nasal and oronasal masks in a randomized order, 14 days apart. Data and fluids were analyzed before and after both titration studies comparing both masks including supine and lateral position during asleep and CPAP titration. Third phase for OSA patiens: patients were treated with the best interface found in CPAP titration study during 30 days and patients were assessed for sleep quality, excessive sonolence during the day, airway symptoms, airway defense mechanisms biomarkers (mucociliary clearance, mucus properties, citology, inflammation cytokines and adhesion molecules and others) and serum cytokines and miRNA.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-900
    • Instituto do Coração - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 01246-903
      • Faculdade de Medicina da Universidade de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• >21 years
• moderate or severe obstructive sleep apnea
• nonsmokers
• ex smokers (cessation >12 months)

Exclusion Criteria:

• infection / acute respiratory inflammation (30 days after to study entry)
• history of fixed nasal obstruction
• nasal or upper airways surgery
• chronic diseases without optimized treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nasal CPAP during titration; Group nasal mask: use of CPAP for one night whit wash out of two weeks	Device: Nasal CPAP; use of nasal mask to titrate CPAP during a manual full night: if nasal mask is the best interface during titration compared with oronasal mask - patients will go 30-day period of treatment; Other Names: Nasal mask
Experimental: Oronasal CPAP during titration; Group oronasal mask: use of CPAP for one night with wash out of two weeks.	Device: Oronasal CPAP; use of oronasal mask to titrate CPAP during a manual full night: if oronasal mask is the best interface during titration compared with nasal mask - patients will go 30-day period of treatment; Other Names: Oronasal mask

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Apnea-Hypopnea Index	A full-night diagnostic polysomnography (PSG) was performed in each subject to determine the stages of sleep, an electroencephalogram, electro-oculogram and electromyogram of the submentalis muscle were obtained. Peripheric blood oxygenation was recorded with the use of a finger pulse oximeter. Thoracoabdominal excursions were measured qualitatively using respiratory effort sensors placed over the ribcage and abdomen. Snoring was detected with a vibration snore sensor and body posture with a body position sensor. Subjects used a molded single-piece translucent silicone rubber mask. During titration, a mask with CPAP was added and the procedure was performed according to AASM guidelines.	Baseline (Time 0), after CPAP titration with nasal and oronasal mask (one night with wash out of two weeks) and after 30-day period of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway inflammation by exhaled breath condensate pH	The EBC sample was collected over 15 min of quiet and normal breathings (regular tidal volumes and respiratory rate) through a mouthpiece that was connected to a collector device. Participants were asked to avoid to eat green vegetables and canned or embebbed food the 24 hours before measurements. Ph measurements were performed after dearation with ultrapure argon gas (99.9%).	Participants will be assessed at baseline (Time 0), nasal CPAP, oronasal CPAP and after 30-day CPAP treatment (30 days)
Nasal mucociliary clearance by saccharine transit time	We evaluate the nasal MCC by measuring nasal saccharine transport time (STT). The subject was asked to avoid alcohol, tea and coffee for 6 hours and to eat or drink nothing for 2 hours before the measurements. The STT assessment is performed in a quiet room at a temperature of 21-22ºC and relative humidity of 63-71%. Subjects sat in a chair and are asked to maintain regular breathing, to avoid deep breathing, coughing, sneezing, sniffing or talking during STT measurements. Twenty-five µg saccharin particles are deposited 2 cm from the anterior end of the non-obstructed nostril and the timer is stopped at the first perception of sweet taste. The maximum delay between the deposition and perception is set at 60 minutes for non-detection.	Participants were assessed at at baseline (Time 0), nasal CPAP, oronasal CPAP and after 30-day CPAP treatment (30 days)
Nasal inflammation by pH, citology and cytokines and adhesion molecules in nasal lavage	TNF-α, IL-1beta, IL-6, IL-8, IL-10, IL-13, IL-17, MPO, MIPs, MMPs and cardiovascular panels (multiplex bead assay, Millipore, USA) using ELISA in nasal lavage.	Participants were assessed at baseline (Time 0) and after nasal titration, oronasal titration and CPAP treatment (30 days)
Sleep quality by Pittsburg Questionnaire	It is a questionnaire to assess the quality of sleep (basically 7 components) - cut off >5: the worst quality	Participants will be assessed at at baseline (Time 0) and after CPAP treatment (30 days)
Upper airways symptoms by SNOT20 questionnaire	This is a questionnaire that aims to assess quality of life of patients with chronic upper airways symptoms	Participants will be assessed at at baseline (Time 0) and CPAP treatment (30 days)
Excessive sonolence during daytime by Epworth Sleepiness Scale	This is a questionnaire about daytime sleepiness with 8 questions. Cut-off >10: yes	Participants will be assessed at at baseline (Time 0) and CPAP treatment (30 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokines, adhesion molecules and miRNAs in serum	TNF-α, IL-1beta, IL-6, IL-8, IL-10, IL-13, IL-17, MPO, MIPs, MMPs and cardiovascular panels (multiplex bead assay, Millipore, USA) using ELISA in nasal lavage. For miRNA PCR analysis, RNA was extracted from the blood sample, quantified and analysed.	Participants will be assessed at at baseline (Time 0) and CPAP treatment (30 days)
adherence to CPAP	we assessed the time use by CPAP device card	1 and 12 months
CPAP level	Using two full-nights polysomnography for CPAP titration. To determine the appropriate CPAP level with nasal and oronasal masks	CPAP titration with nasal and oronasal mask (one full night for each mask )
PSG variables	All variables were provided by the study with PSG according to AASM guidelines	At baseline and after CPAP titration with nasal and oronasal mask (one full night for each)

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo; Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Investigators: Principal Investigator: Juliana A Nascimento, PhD, Faculdade de Medicina da Universidade de Sao Paulo; Study Director: Naomi K Nakagawa, PhD, Faculdade de Medicina da Universidade de Sao Paulo; Study Chair: Geraldo Lorenzi-Filho, PhD, Heart Institute - Hospital Das Clinicas Da Faculdade de Medicina Da Universidade de São Paulo

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (Estimate): October 24, 2014

Study Record Updates

• Last Update Posted (Actual): April 19, 2018
• Last Update Submitted That Met QC Criteria: April 17, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: CPAP; obstructive sleep apnoea; nasal mask; oronasal mask; breathing route
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: CEP 102/13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO