Fractional Exhaled Nitric Oxide and CRP Levels in Egyptian Patients With Obstructive Sleep Apnea Syndrome
Condition: OSA
MeSH terms: Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Interventional

Summary: 
      Obstructive sleep apnea syndrome (OSAS) was associated with upper and lower respiratory tract
      inflammation, Fractional exhaled nitric oxide (FeNO) proposed as a marker of airway
      inflammation, few studies were done on the impact of continuous positive airway pressure
      (CPAP) on FeNO.

      Aim of the work: to study the impact of continued positive airway pressure therapy on exhaled
      NO and using Hs-CRP as a marker of inflammation in obstructive sleep apnea syndrome.

      Patient and Methods: This study is a case-control study including participants were newly
      diagnosed as OSAS and control recruited from sleep outpatient clinic, full night PSG was
      done, fractional exhaled nitric oxide and Hs-CRP were measured next morning of PSG, CPAP for
      moderate to severe OSA patient was advised with measurement of FeNO and Hs-CRP after 3months
      of CPAP Keywords: FeNO; Hs-CRP; CPAP; OSA. This research did not receive any specific grant
      from funding agencies in the public, commercial, or not-for-profit sectors.
    

Detailed description: 
      This study is a prospective 3 months follow up study including only (27) participants as a
      convenient sample for the cost limitations newly diagnosed as OSA and (10) healthy control.

      inclusion characters All participants enrolled in this study

        1. were ≥ 18 years old,

        2. non-smokers and

        3. excluded from any inflammatory disorders (allergy, bronchial asthma, gastro-esophageal
           reflux disease, cardiovascular diseases, and cerebrovascular diseases) or use of any
           regular medication including (nasal/inhaled/oral corticosteroids, antihistaminic,
           cysteinyl leukotriene receptor inhibitors), or

        4. had an upper or lower respiratory tract infection 2 weeks prior to sampling. Control
           healthy subjects were also free from any sleep disorders symptoms. Cases were recruited
           from Sleep-disordered breathing unit out Patient Clinic in pulmonary medicine department
           - Mansoura University - Egypt. All participants in this study were evaluated by history
           taking with stress on OSAS questionnaires, anthropometric parameters measurement and
           spirometric pulmonary function (FEV1, FVC and FEV1/FVC ) all patients were subjected to
           laboratory, attended, full-night polysomnography using (SONMOscreenTMplus, SOMNOmedics,
           (Germany) with AASM standard montage, This included a standardized montage: two-channel
           electroencephalograms (EEG; C4/A1, C3/A2), bilateral electrooculogram (EOG), submental
           electromyogram (EMG), bilateral leg EMGs, and electrocardiography (ECG). Airflow was
           measured using a thermistor (Healthdyne Technologies), the respiratory effort was
           assessed by inductance plethysmography and oxygen saturation was recorded using a finger
           probe. The oxygen saturation signal was digitally sampled at 1 Hz and stored both on the
           PSG record and in a separate monitor for offline analysis.

      studies were interpreted according to the last manual scoring criteria. The cases were
      diagnosed as severe OSA according to the third international classification of sleep
      disorders. Then they were classified according to apnea-hypopnea index (AHI) into two main
      groups: cases (AHI ≥5) (n=) and control (AHI˂5) (n=10). Cases were classified into two
      subgroups into severe OSA (AHI ≥ 30) (n=34) and moderate OSA (AHI (15-30) mild (n=10).

      On the next morning of the study 30 min after PSG, the blood sample was collected for
      measuring of high sensitivity C- reactive protein (HS-CRP) by (The Immunospec Hs-CRP) ELISA,
      based on the principle of a solid phase enzyme-linked immunosorbent assay [15]. The assay
      system utilizes a unique monoclonal antibody directed against a distinct antigenic
      determinant on the CRP molecule.

        1. fractional exhaled nitric oxide (FeNO) measurement: was measured by (NO breath®FeNO
           monitor-Bedfont scientific Ltd) according to international recommendations [16], with a
           single breath online method at constant flow of 50 mL/s or 12 seconds of exhalation of
           adults with a sensitivity of one part per billion (ppb) Calibration of the analyzer was
           automatically performed by the software. Briefly, after inhaling to total lung capacity,
           the subjects exhaled through a mouthpiece into an exhalation circuit. All subjects were
           asked to stop eating, drinking, and strenuous exercise for two hours prior to FeNO
           measurement.

        2. CPAP therapy and follow up: 22 of 27 patients with moderate and severe OSA were advised
           to use CPAP therapy after full-night CPAP titration study in accordance with AASM
           recommendations [17]Preliminary education and adaptation for CPAP was performed 1hour
           prior to the beginning of CPAP titration.

           An optimal titration study was defined as one in which an optimal CPAP pressure was
           reached that normalizes the AHI and eliminates snoring, desaturation, and arousals, and
           restores a normal flow contour [17] adjusted prescribed CPAP pressure after titration
           was administered during sleep for at least five hours per night, for at least five days
           per week for three consecutive months.

        3. follow up sessions after CPAP therapy: were adjusted 1,2 and 3 months after starting
           CPAP therapy for evaluation of patients response and compliance to CPAP, Adherence to
           the CPAP therapy was evaluated after revision of the download information from the CPAP
           device.

           Adherence was defined as CPAP use for an average of 4 h on

           ≥ 70% of the nights.

        4. (FeNO) was also measured in the three follow up visit with CPAP follow up, however, BMI,
           spirometric pulmonary function(FEV1, FVC, and FEV1/FVC ) and high sensitivity C-
           reactive protein (HS-CRP) were measured after 3 months in last follow up visit of the
           study.

      Five patients from 27 were lost in follow up sessions because they did not use CPAP.

      Then data were analyzed using SPSS version 16 for Windows® (SPSS Inc, Chicago, IL, USA).
      Qualitative variables were presented as numbers and percentages. Chi-square test or Fisher
      exact test of significance was for comparison between groups, as appropriate. Quantitative
      variables were presented as mean ±SD. They were tested for normality distribution by the
      Kolmogorov-Smirnov test. In normally distributed variables unpaired t-test (t) was used. In
      abnormally distributed variables independent Mann-Whitney test (Z) was used. P-value ≤0.05
      was considered statistically significant. For the detection of cut off points, we use the
      receiver operating characteristic (ROC) curve. Sensitivity, Specificity values were used for
      studying the selected cut off point for validation as a screening tool.
    

Intervention name(s): Fractional exhaled nitric oxide and CRP levels
Intervention type(s): Diagnostic Test
Intervention description(s): measurement of FeNO and Hs-CRP after 3months of CPAP
Intervention MeSH terms: Nitric Oxide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: FeNO; ;;; Hs-CRP; CPAP; OSA