Markers in Exhaled Breath Condensate in Obstructive Sleep Apnoea (OSA) Patients

January 21, 2010 updated by: Chinese University of Hong Kong

To Assess the Differences in Chemokines and Oxidative Stress Markers in Exhaled Breath Condensate of Obstructive Sleep Apnoea Patients

Patients with obstructive sleep apnoea (OSA) have repetitive episodes of partial or complete upper airway obstruction during sleep. This leads to sleep fragmentation and symptoms like excessive daytime sleepiness and impaired psychosocial well-being. More evidence now suggested OSA is associated with cardiovascular diseases like hypertension, myocardial infarction, pulmonary hypertension and stroke.

The upper airway structure and function are altered in OSA. Some studies suggested that an increase in the levels of systemic biomarkers of inflammation and oxidative stress in patients with OSA. So far, there is only very limited data on non-invasive monitoring of inflammation involved in the upper airway of OSA patients. The inflammatory mechanisms involved in the upper airway may give some insights to the systemic effect, like cardiovascular complications, of OSA.

Measurement of the constituents of exhaled breath and exhaled breath condensate (EBC) is a non-invasive method to assess the degree of inflammation of the airway. Exhaled nitric oxide (eNO) can be measured with the subject exhaling to a mouthpiece connected to a machine measuring real-time eNO level. With the subject exhaling to a cooling unit, EBC can be collected as liquid is formed as a result of condensation.

This study will assess the eNO in exhaled breath, oxidative stress marker (8-isoprostane) and cellular inflammatory markers (eotaxin, monocyted derived chemokine, growth related oncogene- alpha, monocyte chemoattractant protein-1) in the EBC and blood of OSA patients before and after 1 night and 3 months of continuous positive airway pressure treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Measurement of exhaled Nitric Oxide and collection of exhaled breath condensate and peripheral blood. This will be done 2 to 4 times(on admission,the morning after sleep study,immediately after CPAP titration, after CPAP use for 3 months). Each time eNO will be measured first, followed by EBC collection.

For the tests in the morning, patients will be asked to postpone his/her breakfast until after the test which will take less than half an hour.

OSA is defined as patients having a respiratory disturbance index of ≥5/hr.

Measurement of Exhaled Nitric Oxide:

eNO will be measured using a Sievers 280i chemiluminescence analyser (Sievers Instruments, Boulder, CO, USA) sensitive to NO from 1 ppb to 200 ppm and with a resolution of 1 ppb and accuracy of 1 ppb designed for online recording. The eNO measurement will be performed according to ATS standards. Briefly, subjects should remain seated without nose clip during the procedure, with 2-minute rest between eNO measurements. The eNO will be measured online at an expiratory flow rate of 50 ml/sec, a dead space of 10 ml and 2-second plateau duration. Repeated exhalations are performed until three NO plateau values agree at the 10% level or two agree at the 5% level. The mean NO value will then be recorded.

Collection of Exhaled Breath Condensate:

EBC will be collected using the ECoscreen (Jaeger, Germany) according to manufacturer instructions. After rinsing their mouth, the recruited subjects will breathe tidally through a mouthpiece that is connected through a unique one-way valve into a cooled collection tube where vapours, aerosols and moisture in the breath condense along the walls of the tube. The one-way valve is then used as a plunger that collects droplets stuck to the inside wall and holds the sample near the top of the tube. The device inherently prevents salivary contamination as shown by the absence of salivary amylase in EBC. On average, this device will be able to collect 300 microL per minute of EBC for an adult. Each subject will be asked to breathe through the collection kit for 5 minutes, which should be sufficiently long to yield 1 ml of condensate for inflammatory marker analysis. EBC will be stored immediately at -70oC until analysis for inflammatory markers.

Measurement of 8 isoprostane, GRO alpha, MCP1, eotaxin and MDC levels in exhaled breath condensate:

EBC stored at -70oC will be analysed for 8-isoprostane, GROalpha, MCP1, eotaxin and MDC levels concentrations in batches. We will use 96-well polystyrene microplates coated with murine monoclonal antibodies against human 8 isoprostane, GRO alpha, MCP1, eotaxin and MDC levels. The levels of these markers in EBC will be measured in duplicates by sandwich enzyme immunoassay (R & D Systems, Minneapolis, MN, USA) according to instructions provided by the manufacturer.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
    • N.t.
      • Shatin, N.t., Hong Kong, 000
        • Prince of Wales Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients will be recruited upon admission for sleep study under the Division of Respiratory Medicine, Prince of Wales Hospital.
  • Patients who are aged 18 to 60 will be recruited.

Exclusion Criteria:

  • Known history of respiratory disease that will affect inflammatory markers in EBC like asthma, chronic obstructive pulmonary disease and bronchiectasis.
  • Upper or lower respiratory tract infection within 6 weeks from the study.
  • Current smokers, or ex-smoker who quitted for less than a year.
  • Pregnant subjects.
  • Any form of malignancies or serious medical illness that will affect the survival of the subject significantly in 1 year period.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
CPAP
Device: CPAP
Continuous positive pressure device with a time clock
Placebo Comparator: 2
no CPAP
Device: placebo
no CPAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes in the biomarkers in breath over a period of time in subjects with CPAP and no CPAP treatment for the OSA
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Investigators

  • Principal Investigator: Fanny WS Ko, MBChB, CUHK

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

February 6, 2006

First Submitted That Met QC Criteria

February 6, 2006

First Posted (Estimate)

February 7, 2006

Study Record Updates

Last Update Posted (Estimate)

January 22, 2010

Last Update Submitted That Met QC Criteria

January 21, 2010

Last Verified

January 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Resp/ko/2006/002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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