Respiratory and Endothelial Dysfunctions in Case of Obstructive Sleep Apnea-Hypopnea Syndrome

Abstract

Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) is commonly associated to cardiovascular involvements by an endothelial dysfunction mechanism. Objective: Confirm respiratory dysfunction and analyze the central and peripheral vascular dysfunction in cases of OSAHS. Methods: It is a cross-sectional study on 49 adult subjects: 23 suffering from OSAHS and 26 obese controls. All subjects underwent polysomnography or sleep polygraphy, lung function tests (total body plethysmography, measure of transfer factor of the lung for carbon monoxide (DLCO) and Fraction of Exhaled Nitric Oxide (FeNO)), Laboratory tests, and measurement of endothelial function by evaluating endothelium dependent vasodilatation (VDED) upon the combination of acetylcholine iontophoresis and blood flowmeter by Laser Doppler. Results: A significant decrease in lung function is noted in patients with OSAHS compared to controls. Indeed the OSAHS group has a tendency to pulmonary restriction with an abnormal DLCO and to bronchial inflammation (increased FENO) when compared to control group. A greater impairment of VDED in all patients with OSAHS than in healthy is also confirmed. Conclusion: The abnormality of alveolar-capillary diffusion in apneic patients can be explained in part by bronchial inflammation and endothelial dysfunction.

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The General Surgeon
2019 | Volume 1 | Article 1014
051
© 2019 - Medtext Publications. All Rights Reserved.
ISSN 2687-7007
Respiratory and Endothelial Dysfunctions in Case of
Obstructive Sleep Apnea-Hypopnea Syndrome
Sonia Rouatbi1,2, Ines Ghannouchi1, Rim Kammoun1, Ridha Bechikh3 and Helmi Ben Saad1,2
1Laboratory of Physiology and Explorations, Faculty of Medicine Sousse, University of Sousse, Tunisia
2Heart Failure (LR12SP09) Research Laboratory, Farhat Hached Hospital, Sousse, Tunisia
3Laboatory of Physiology, Faculty of Medicine Monastir, University of Monastir, Tunisia
Citation: Rouatbi S, Ghannouchi I, Kammoun R, Bechikh R, Saad HB.
Respiratory and Endothelial Dysfunctions in Case of Obstructive Sleep
Apnea-Hypopnea Syndrome. Gen Surg. 2019; 1(3): 1014.
Copyright: © 2019 Sonia Rouatbi
Publisher Name: Medtext Publications LLC
Manuscript compiled: Dec 06th, 2019
*Corresponding author: Sonia Rouatbi, Laboratory of Physiology and
Explorations, Faculty of Medicine Sousse, University of Sousse, Mohamed
Karoui Street, 4000 Sousse, Tunisia, E-mail: sonia.rouatbi@gmail.com
Abstract
Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) is commonly associated to cardiovascular involvements by an endothelial dysfunction mechanism.
Objective: Conrm respiratory dysfunction and analyze the central and peripheral vascular dysfunction in cases of OSAHS.
Methods: It is a cross-sectional study on 49 adult subjects: 23 suering from OSAHS and 26 obese controls. All subjects underwent polysomnography or sleep
polygraphy, lung function tests (total body plethysmography, measure of transfer factor of the lung for carbon monoxide (DLCO) and Fraction of Exhaled Nitric
Oxide (FeNO)), Laboratory tests, and measurement of endothelial function by evaluating endothelium dependent vasodilatation (VDED) upon the combination
of acetylcholine iontophoresis and blood owmeter by Laser Doppler.
Results: A signicant decrease in lung function is noted in patients with OSAHS compared to controls. Indeed the OSAHS group has a tendency to pulmonary
restriction with an abnormal DLCO and to bronchial inammation (increased FENO) when compared to control group. A greater impairment of VDED in all
patients with OSAHS than in healthy is also conrmed.
Conclusion: e abnormality of alveolar-capillary diusion in apneic patients can be explained in part by bronchial inammation and endothelial dysfunction.
Keywords: DLCO; Endothelial function; Lung function; Exhaled nitric oxide; OSAHS
Research Article
Introduction
Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS), dened
as Apnea-Hypopnea Index (AHI)>10/h [1-4], currently represents a
real public health problem, with an adult prevalence of 2% to 4% [5].
e origin of sleep apnea may be central (stopping central control
of breathing) or constitutional device, due to an abnormality of the
upper airways or dilator muscles of the pharynx. Obstructive apnea
corresponds to a stop of the naso-oral ventilation with persistence
of thoraco-abdominal movements [6]. Severe snoring and daytime
somnolence clinically evoke the diagnosis of OSAHS, but there are
no specic symptoms [7]. Polysomnography in the sleep laboratory
remains the main tool for diagnosis of OSAHS [8,9].
Although the prevalence of dierent ventilatory defects in OSAHS
is poorly known and the studies analyzing their plethysmographic
prole are contradictory [10], ventilatory variables remain considered
as predictive factors of mortality and morbidity for patients having
OSAHS [11,12]. It is true that the realization of a plethysmography
is not systematic in OSAHS since it is recommended only in certain
situations: obesity, smoking and presence of respiratory symptoms
[8,9,13]. However international respiratory societies recommend
their use for the diagnosis of any ventilatory dysfunction. is is why
we think it is interesting to establish the plethysmographic prole of
patients with OSAHS as well as that of the controls according to the
recent international recommendations [10,11,14].
e OSAHS can have many serious consequences: metabolic,
behavioral or cardiovascular (coronary insuciency, hypertension)
[6,7,13,15-17]. ese latter consequences are common in patients with
OSAHS, but the underlying mechanisms of this association are largely
unknown. Several hypotheses evoke an alteration of endothelial tissue
as a mechanism of these vascular complications in case of SAHOS
[18]. us, the evaluation of the endothelium-dependent response of
the peripheral vessels seemed important to us to study the SAHOS-
vascular endothelial relationship. us, the objectives of this work are
• To compare the respiratory function of patients with OSAHS
compared with obese non-apneic patients.
• Evaluate pulmonary and peripheral vascular dysfunction case
of OSAHS by measuring carbon monoxide transfer capacity
(DLCO) and peripheral vascular reactivity respectively.
Materials and Methods
Study design
is is a cross-sectional study conducted in the physiology and
functional exploration laboratory. e studied sample is composed of
two groups of adults aged 20 years to 65 years. A control group G1
that is composed of 25 subjects obese and free from any respiratory
disease. A group of apneic subjects (G2, N=23) who consulted for
excessive daytime sleepiness and snoring at the Sleep Pathology Unit
and an OSAHS was diagnosed by polysomnography. Subjects from
G2 have the following characteristics: an age between 20 years and 65

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The General Surgeon
2019 | Volume 1 | Article 1014
years old, obesity and a conrmed OSAHS with an AHI greater than
or equal to 10.
Subjects with one or more of the following criteria were excluded
from the study [18]: An intercurrent respiratory infection of the
upper or lower respiratory tract, an asthmatic disease or Chronic
Obstructive Pulmonary Disease (COPD), a known neuromuscular
pathology, an upper airway abnormality, imperfect performance of
required breathing maneuvers, and smoking >10 pack year [19].
Survey
All subjects responded to a standardized questionnaire seeking
inclusion and non-inclusion criteria, respiratory function signs
(cough, dyspnea, expectoration, snoring, daytime sleepiness) and
anthropometric characteristics: Sex, Age (years), Weight (Kg), Height
(m) and Body Mass Index (BMI, kg/m2) calculated according to
the BMI formula = Weight/Height2. Based on BMI value, 3 classes
of obesity have been dened according to WHO are Obesity class 1:
BMI between 30 kg/m2 and 34.9 kg/m2, Obesity class 2: BMI between
35 kg/m2 and 39.9 kg/m2 and Obesity class 3: BMI greater than 40 kg/
m2 [20,21].
Functional respiratory explorations: Total body
plethysmography
All patients and subjects of the study performed a total body
plethysmography using "ZAN 500" equipment (Messgeraete
GmbH2000, Germany).
As recommended by recent international guidelines, ventilatory
variables are interpreted according to local reference values [11]. e
total body plethysmography allows the measurement of ventilatory
ows (forced expiratory volume at the rst second (FEV1, l/s and %),
median maximum expiratory ow (MEF25-75, l/s and %), maximum
expiratory ow at x% of FVC (MEF25 and MEF50, l/s and %)). e
measured pulmonary volumes are: slow vital capacity (VC; l and %),
forced vital capacity (FVC; l and %), FEV1/VC ratio (%),total lung
capacity (TLC, l and %) and residual volume (RV, l and %).
Measured parameters by plethysmography are considered
diminished when they are below the Lower Limit of Normal (LLN).
e LLN is determined from the specic reference values of the
Tunisian population [22].
In this study, we dened dierent ventilatory defects: proximal
obstructive ventilatory defect is when the ratio FEV1/VC or FEV1/
FVC is lower than the LLN [11]. Distal obstructive ventilatory decit
is dened when the FEV1/FVC ratio is normal, the FVC is normal
and MEF25 or MEF50 or MEF25-75 is less than the LLN. A restrictive
ventilatory defect is dened by the TLC which is lower than LLN.
Static pulmonary distension is dened as an increase in RV that is
greater than the Upper Limit of Normal (ULN) [11].
Measure of carbon monoxide transfer capacity (DLCO)
DLCO (mmol/KPa/min) is measured by the inspiratory apnea
method. is parameter is considered diminished when it is lower
than the LLN [11].
Polysomnography
Overnight PSG is performed using DeltaMed (France, Coherence
4 NT) and Nihon Kohden (Japan, 2011) for PSG performed
aer 2012. Sleep states were assessed by recording biopotentials
(electroencephalogram, electromyogram, electrooculogram),
qualitative recordings of respiratory eort (piezo sensors), airow
(thermal sensors), and oxygen saturation (pulse oxymetry). e
sampling frequency for the equipment DeltaMed is 256Hz and 500Hz
for Nihon Kohden. Respiratory events are apneas and hypopneas.
Obstructive apnea is dened as naso-oral airow arrest for at least 10
seconds with persistent ventilatory eorts during apnea [1,3,6].
Hypopneas are dened as a reduction of more than 50% of the oro-
nasal ow amplitude during 10 sec, accompanied by 3% desaturation
and/or arousal. e AHI is the number of apneas and hypopneas per
hour of sleep [23,24]. e severity of OSAHS is dened according to the
value of AHI: light OSAHS AHI<15, moderate OSAHS: 15<AHI<30,
severe OSAHS: AHI>30 [25]. Polysomnographic scoring and staging
are based on Rechtschaen and Kales study, and episodes of arousals
are assessed according to the guidelines in the previous studies [26].
Measurement of exhaled nitric oxide
Exhaled Fraction of Nitric Oxide (FeNO) is measured by
the Mediso HypAir method using an electrochemical analyzer
(Mediso, Sorinnes, Belgium). It is based on the chemiluminescence
method [27]. e instrument has been calibrated and used according
to the manufacturer's instructions. e measurement of FeNO is
made following the international recommendations. ree acceptable
measurements are taken at a ow rate of 50 ml/s at 15 minutes as
recommended by the ATS/ERS. e average of the three valuesis used.
FeNO is expressed in parts per billion (ppb), which is the equivalent
of nanoliter per liter [27].
Endothelial function study: Laser Doppler
A technique studies the microcirculation and can therefore
visualize the subcutaneous blood ow variation (qualitative and local
measurement) by noninvasive probe. Before starting the recording
certain conditions are respected: no major eort before the test, the
examination room is air-conditioned at a temperature around 30°C
and ensure that the patient does not wear clothing or jewelry that may
interfere with the recording [13,28-30]. e principle of this technique
is to measure the spectral variations of a light reected by red blood
cells and emitted by a helium-neon laser with a wavelength of 632 nm.
ese variations depend on the speed and number of red blood cells,
hematocrit, tissue optic properties and vascular network geometry
[31]. Calibration of the device is checked at least once a month. Laser
Doppler prole is interpreted independently of the other proles.
Indeed, no threshold or normal value is determined or published.
Variations in the endothelial response to acetylcholine injection
(ΔACH) are, therefore, measured and interpreted with reference
to baseline, which is the baseline of endothelial changes measured
during the rst two minutes of the maneuver before any injection of
acetylcholine (ACH), 3 successive doses of ACH are injected followed
by an increase in local skin temperature. us the variations of the
endothelial response following the 3 acetylcholine injections and the
temperature increase are measured (ΔACH1, ΔACH2, ΔACH3 and
ΔTemp) [31].
Statistical analyzes
e statistical analyzes are performed using the Statistica soware
(Statistica Kamel version 6.0, Stat So, France). In a rst step and
aer checking the normal distribution of the studied parameters,
we determine the means and the standard deviations of all the
quantitative variables (anthropometric and ventilatory) for both
G1 and G2 groups of the study. e Mann Whitney U test is used
to compare the quantitative variables (endothelial and respiratory
parameters) of the two groups. Comparison of categorical variables

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The General Surgeon
2019 | Volume 1 | Article 1014
(sex-ratio, Smoking habit, hypertension and diabetes…) between
groups is set by chi-square test. e degree of signicance is set at p
lower than 0.05.
Results
Forty eight subjects were included in the study and beneted from
the dierent tests. ey were divided into two groups: e G1 group is
the control obese group (N=25 with a sex ratio (M/F) = 16/9) and the
G2 group is formed of 23 OSAHS patients (sex ratio (M/F) = 16/7).
ese apneic patients had an Epworth sleepiness score of 13.78 ± 4.92,
an AHI>10 with an oxygen saturation average of 89.30 ± 6.43% and a
number of desaturations per night of sleep at 443.78 ± 147.72. e G1
group had an AHI<10.
e anthropometric characteristics of the two groups were shown
in Table 1, 21 apneic patients and the entire G1 group had obesity
and 2 from the G2 group were overweight. e comparison of
weight, height and BMI of the two groups did not show a statistically
signicant dierence. e two groups were matched by weight, height,
sex and BMI.
DLCO and %DLCO were decreased in both groups G1 and
G2. 8 from apneic group and 2 from control group had a diusion
abnormality.
e degree of bronchial inammation, judged by FeNO, was
signicantly greater in the apneic group than in the control group and
was correlated with the degree of severity of OSAHS.
Assessment of vascular endothelial dependent response (VDED)
showed a signicantly severe VDED dysfunction in all subjects with
OSAHS compared to healthy subjects. However, following the rise
in temperature, non-vessel-dependent endothelium responses in
both groups were comparable. More severe VDED dysfunction in all
hypertensive apneic patients compared to non-apneic was signicant
(Table 3).
Discussion
e main ndings of this study were
• OSAHS is characterized by a signicant decrease in respiratory
function and an increased bronchial inammation.
• OSAHS altered peripheral and central endothelial function by
altering the regulation of endothelial vasomotion.
e group of non-apneic obese was selected from a group
of patients who were suspected having OSAHS and whose
Control Group
(N=25)
OSAHS Group
(N=23)
Total sample
(N=48) p
Sex-ratio
(M/F) 16-Sep 16-Jul 32/16 0.682(ns)
Age (yrs) 43.53 ± 9.60 50.08 ± 9.28 46.61 ± 9.92 0.0186 (*)
Weight (Kg) 97.00 ± 12.93 100.00 ± 13.20 98.40 ± 13.01 0.264
(ns)
Height (m) 1.68 ± 0.09 1.67 ± 0.09 1.67 ± 0.09 0.909
(ns)
BMI (Kg/m2)34.42 ± 4.63 35.78 ± 4.72 35.06 ± 4.68 0.179
(ns)
Smoking
habit (yes/no) Oct-15 12-Nov 22/26 0.397
(ns)
Diabetes (yes/
no) Oct-15 Oct-13 20/28 0.807
(ns)
Hypertension
(yes/no) Apr-21 Oct-15 14/34 0.036 (ѳ)
Table 1: e anthropometric and clinical characteristics of the two groups of
the study.
M: Male and F: Female
OSAHS: Obstructive Sleep Apnea Hypopnea Syndrome
BMI: Body Mass Index (Weight (Kg)/Height (m2))
ns: not signicant dierence between control and OSAHS groups by Mann
Whitney U-test
*: p value <0.05, comparison between control and OSAHS groups by Mann
Withney U-test
ѳ: p value<0.05, comparison by chi-square test between control and OSAHS
groups of categorical variables (sex-ratio, Smoking habit, Hypertension,
Diabetes).
Twenty tow patients (12 from apneic group) were active smokers.
e comparison of smoking in both active and passive forms between
the two groups showed no signicant dierence. 14 patients (10
from G2) had an arterial hypertension. 20 patients (10 from G2) had
diabetes mellitus (Table 2).
Proximal ows (FEV1; l/s and %) and distal ows (MEF25-75,
MEF25, MEF50) values were signicantly lower in apneic patients
than in controls. Five apneic patients and no one from control group
had proximal obstructive ventilatory defect. No signicant dierence
was found between the two groups concerning distal obstructive
ventilatory defect (5 from controls and 8 from apneic subjects).
Vital capacity, forced vital capacity and total lung capacity were
signicantly lower in apneic patients compared to controls. A restrictive
ventilatory decit was present in 26 subjects (16 from apneic group).
Control Group OSAHS Group Total Sample p
FEV1 (L) 3.26 ± 0.70 2.59 ± 0.75 2.95 ± 0.79 0.005
%FEV1 98.65 ± 11.86 82.56 ± 15.30 91.10 ± 15.70 <0.001
MEF50 (L/s) 4.45 ± 1.14 3.72 ± 1.21 4.11 ± 1.21 0.057
%MEF50 97.76 ± 22.63 85.263 ± 26.36 91.89 ± 25.00 0.057
MEF25 (L/s) 1.43 ± 0.50 1.20 ± 0.57 1.33 ± 0.54 0.217
%MEF25 74.23 ± 21.81 69.35 ± 35.28 71.94 ± 28.71 0.412
MEF25-75 (L/s) 3.51 ± 0.90 2.99 ± 0.93 3.26 ± 0.94 0.062
%MEF25-75 89.30 ± 19.24 78.95 ± 26.18 84.45 ± 23.11 0.138
VC (L) 3.98 ± 0.90 3.25 ± 0.96 3.64 ± 0.99 0.017
%VC 98.11 ± 14.5 83.01 ± 12.59 91.03 ± 15.51 <0.001
FVC (L) 4.00 ± 0.94 3.14 ± 1.02 3.60 ± 1.06 0.006
%FVC 100.42 ± 13.08 82.61 ± 14.03 92.06 ± 16.12 <0.001
FEV1/FVC (%) 82.30 ± 6.27 79.30 ± 9.12 80.89 ± 7.81 0.412
RV (L) 1.66 ± 0.50 1.65 ± 0.72 1.66 ± 0.61 0.525
%RV 89.6 ± 21.98 83.82 ± 31.51 86.89 ± 26.75 0,241
TLC (L) 5.65 ± 1.21 4.76 ± 1.28 5.23 ± 1.31 0.018
%TLC 93.38 ± 13.70 78.95 ± 11.91 86.61 ± 14.69 <0.0001
DLCO (mmol/
KPa/min) 10.70 ± 2.40 8.70 ± 2.40 9.800 ± 2.60 0,008
%DLCO 112.10 ± 20.20 92.70 ± 22.00 103.00 ± 23.00 0.001
FeNO (ppb) 18.40 ± 9.20 31.30 ± 13.60 24.85 ± 11.40 <0.0001
Table 2: Respiratory functional characteristics of the two groups of the study:
OSAHS group and control group.
FEV1: Forced Expiratory Volume at the rst second (l and %)
VC: Vital Capacity (l and %)
FVC: Forced Vital Capacity (l and %)
FEV1/VC ratio (%)
MEF25-75: Median Maximum Expiratory Flow (l/s and %)
MEF25 and MEF50: Maximum Expiratory Flow at 25 and 50% of FVC (l/s
and %)
TLC: Total Lung Capacity (l and %)
RV: Residual Volume (l and %)
DLCO: carbon monoxide transfer capacity ( mmol/KPa/min and %)
FeNO: Fraction of Exhaled Nitric Oxide
ns : not signicant dierence between control and OSAHS groups by Mann
Whitney U-test
p of signicance, comparison between control and OSAHS groups by Mann
Withney U-test.

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The General Surgeon
2019 | Volume 1 | Article 1014
polysomnography or polygraphy did not conrm this diagnosis. Some
subjects of this group were selected from an obese, volunteer and
healthy group (BMI> 30 kg/m2). is group was used to determine the
eect of OSAHS alone on respiratory and cardiovascular functions
by comparing apneic obese patients with non-apneic obese subjects.
e group of apneic patients was selected aer the conrmation of an
OSAHS by polysomnography.
All respiratory and vascular functional explorations were
performed by the same operator and at the same timing, in the morning
for all patients, to respect the reproducibility of the measurements and
to avoid circadian variations in respiratory function.
e group of apneic patients (N=23) had a male predominance
(16 men) which is oen found in the carriers of a SAHOS [8,32-34].
e exact mechanisms of this predisposition were not clear, but it
could be explained by an underestimation of the number of women
with OSAHS. Indeed, Young et al. [35] estimated that 93% of apneic
women were undiagnosed. In addition, male predominance could be
related to anatomical factors at upper airways: e increase in neck
circumference and the important collapsibility of upper airways in
men [36,37]. Aer menopause, this dierence tended to disappear
because of the disappearance of the protective hormonal climate of
the woman [38]. It has been reported that testosterone increased the
collapse of upper airways and that progesterone played a protective
role in maintaining good upper airways permeability [39].
e average age of our apneic patients (50 ± 9 years) was
comparable to those in the literature. In fact, the majority of patients
with OSAHS were older than 50 years [5,12]. ese results conrmed
the accepted classical notion that the prevalence of OSAHS increased
with age [5,12,39,40]. Duran et al. [3] showed that the prevalence of
OSAHS increased with age regardless sex with an odds ratio of 2.2
every 10 years. Age-related anatomical and histopathological changes
in the pharynx led to increased collapses (loss of elastic tissue) of
the upper airways, which may explain the increased prevalence of
OSAHS with age [5,38,40]. Indeed, this hypercollapsibility associated
to a decrease in muscle tone at upper airways during sleep were
responsible for pharyngeal wall vibration and obstructive sleep
apnea. Planchard et al. [5] explained the sleep-related respiratory
disturbances in apneic elderly patients to the aging of ventilatory
control and thoracic mechanical performance.
In this study, all apneic patients were obese with an average
BMI of 35.78 Kg/m2 ± 4.72 Kg/m2. Obesity, especially in its massive
or android form, is a major risk factor for OSAHS [15,16]. Indeed a
10% of gain in body weight could predict an increase in AHI of 32%.
is modication can be explained by the anatomical modications
of UAW. Obesity is responsible of an increase in the compliance of
the pharyngeal walls and the presence of external compression of the
pharynx by the peripharyngeal fatty deposits [15,16].
Abdominal fat found in android obesity could also play an
important role in sleep apnea [4]. Indeed, since the functional residual
capacity is reduced in obese patients, contraction of the diaphragm
can cause signicant intra-thoracic depression at the beginning of
inspiration, which can lead to pharyngeal collapse [36,40].
Spirometric data showed an obstructive ventilator defect in 12
apneic patients and 10 non-apneic obese subjects. e comparison
between apneic and non-apneic groups showed a signicant
dierence in FEV1 with lower FEV1 in apneic patients. is could
be explained by the rise in oxidative stress during SAHOS leading to
a decrease in nitric oxide synthesis by pulmonary tissue and causing
bronchial muscles relaxation defect [12,29,41]. However, FEV1 was
considered by several authors to be an unsuitable tool for assessing
the functional impact of OSAHS since this parameter did not show
a signicant dierence between patients with and without OSAHS
during their studies [9,34,42]. MEF25-75, MEF25 and MEF50 are the
parameters that provide information on small airway obstruction.
However, these parameters depended on the expiratory eort and
especially the patient's cooperation, which was oen dicult to
obtain [11]. In our study, MEF25-75 MEF25 and MEF50 were lower
in G2 than in G1. Also Van Meerhaeghe et al. [43] found a signicant
dierence in MEF25-75 between apneic and non-apneic patients. is
can be explained by obesity that has resulted in pulmonary restriction
with reduced lung volumes and decreased distal ow rates [23,43].
e restrictive ventilator defect was objectied in 10 non-apneic
and 16 apneic obese subjects. is restriction could be explained by
the consumption of tobacco, especially the narghile, which contains
microparticles and heavy metals that can diuse to the deep lung. is
later is oen associated to an abnormal DLCO [44]. Morbid obesity
is associated with a decrease in static and dynamic lung volumes and
an alteration of gas exchange and ventilatory mechanics. e most
severe obese patients had a restrictive involvement characterized by
a decrease in VC, functional residual capacity (FRC), CPT and RV
[41-43]. In our study, VC, FVC, and TLC were signicantly dierent
between apneic and obese patients. Apneic patients had higher loss in
lung volumes than non-apneic obese. DLCO was signicantly lower
in apneic group when compared to the control group. is result
can be explained in part by bronchial inammation and endothelial
dysfunction. Dierent from our results, Hostein et al. [45] in a study
of 1296 apneic patients, found a higher DLCO in apneics. Doré and
Orvoën-Frija [21] concluded that apneic or healthy obese patients had
an increased in DLCO. In our study, the absence of DLCO elevation
could be attributed to the association of two opposite mechanisms
occurring during OSAHS: an increase in pulmonary capillary blood
volume due to obesity and an increase in cardiac output linked to the
hyperactivity of the sympathetic system. ese mechanisms tend to
increase the DLCO. e alteration of the alveolar-capillary membrane
tends to reduce the DLCO. Indeed, during the course of OSAHS,
an increase in atherosclerosis and inammatory manifestations
causing an alteration of the pulmonary exchanger was oen noted
[16,17,46]. e degree of bronchial inammation, demonstrated by
the increase in FeNO values, was signicantly greater in the apneic
group than the control and correlated with the severity of OSAHS.
is increase in FeNO in apneic subjects could be caused by repetitive
Control Group OSAHS Group Total Sample p
ΔACH1 161.5 ± 168.6 66.1 ± 84.3 116.7 ± 142.8 0.006
ΔACH2 322.8 ± 263.6 129.4 ± 135.2 232 ± 220.9 <0.001
ΔACH3 442.6 ± 282.4 200.5 ± 189.1 328.8 ± 269.8 0.001
ΔTem p 1161 ± 807.4 728.9 ± 455 958.2 ± 694.2 0.07
Table 3: Parameters of the microcirculation variation in the two groups of the
stud y.
ns : not signicant dierence by Mann Whitney U-test
p of signicance, comparison by Mann Withney U-test.
ΔACH1: variation of the endothelial response following the rst dose of
acetylcholine.
ΔACH2: variation of the endothelial response following the second dose of
acetylcholine
ΔACH3: variation of the endothelial response following the third dose of
acetylcholine
ΔTemp: variation of the endothelial response following the increase of
temperature.

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2019 | Volume 1 | Article 1014
apnea, hypoxemia during sleep, and upper airways involvement
[29]. In the present study, all patients with OSAHS had lower VDED
than non-apneic obese. ese results thus conrmed the presence of
endothelial dysfunction in subjects with OSAHS compared to healthy
obese controls. is dysfunction was present even in the absence of
hypertension or other cardiovascular diseases suggesting that OSAHS
was an independent risk factor for endothelial dysfunction [29,31,47].
Sanders et al [18] showed the presence of a causal link between
OSAHS and endothelial dysfunction. is result may explain in part
the pathogenic role of OSAHS in hypertension and cardiovascular
disease. In fact, VDED measured aer infusion of acetylcholine
is decreased in subjects suering from OSAHS compared to age-
matched controls and BMI thus indicating the reduction in nitric
oxide bioavailability. Overall, these studies provide direct evidence
of the bioavailability of nitric oxide that is reduced in patients with
OSAHS with or without cardiovascular disease.
OSAHS negatively aects endothelial regulation of peripheral
vasomotricity. is is mainly expressed by the decrease in VDED
and is mainly related to a reduction in the bioavailability of nitric
oxide, a marker of vascular endothelial function, and an increase in
vasoconstrictor substances [13,18,29,47]. Hypoxemia resulting from
repeated apneas does not have the same eect on bronchial tissue
and vascular endothelium. At the bronchial tree it was responsible of
an increase in nitric oxide following inammation of the bronchial
wall (the origin is the bronchial epithelium). At the vascular level this
hypoxemia reduced the production of nitric oxide by vascular smooth
muscle [29,48]. Several hypotheses were mentioned to explain
hypertension in apneics: e sleep fragmentation, intermittent
hypoxemia and sympathetic activation were the most validated.
Yannoutsos et al. objectied the responsibility of endothelial
dysfunction in the occurrence of hypertension [49]. It is well known
that OSAHS is associated with notable non-respiratory morbidity,
including an elevated prevalence of metabolic syndrome, hypertension,
insulin resistance, type 2 diabetes and cardiovascular illnesses,
such as transient ischemic attacks, stroke, cardiac arrhythmias,
myocardial infarction and pulmonary hypertension [50]. Insulin
secretion increases the endogenous release of the potent vasodilator
nitric oxide from the endothelium. Circulating exosomes facilitate
important intercellular signals that modify endothelial phenotype,
and thus emerge as potential fundamental contributors in the context
of OSAHS-related endothelial dysfunction [51]. Exosomes may not
only provide candidate biomarkers, but are also a likely and plausible
mechanism toward OSAHS-induced cardiovascular disease. Recently,
it was shown that levels of 8-isoprostane, though not exhaled nitric
oxide, distinguish children with OSAHS from those with primary
snoring or healthy, correlate with disease severity and closely predict
OSAHS in the whole sample observed [52].
In the present study, an evaluation of non-endothelial dependent
vasodilatation through local warming was also done. e dierence
in means between the apneic and non-apneic groups was not
signicant. us, non-endothelial dependent vasodilatation was
maintained in apneic patients. ese results were comparable to
those found in the literature. e vessel diameter in this case was
similar in patients with OSAHS and control subjects. Similarly, the
percentage increase in vessel diameter in both groups was comparable
(p>0.05) [53]. In fact the non-endothelial dependent vasodilatation
corresponded to the maximum vasodilatation of vessels. It depended
on several vascular structures, particularly smooth muscle cells and
C-bers. It was therefore conceivable that, when a subject had pure
endothelial involvement, the non-endothelial mechanisms involved
in vasodilatation would be preserved. us, the OSAHS represented a
vascular risk factor giving pure endothelial dysfunction.
e main limitations of this study were: First, the sample size
which was reduced to 48 due to the poor cooperation of patients in
performing the respiratory maneuvers. e sample size of this study
appeared to be satisfactory compared to that of the literature [32,33].
Second, the study design age and sex matching which should be
performed for reducing the risk of bias but it was not performed in
this study.
Conclusion
It was conrmed that OSAHS, characterized by a signicant
decrease in respiratory function and bronchial inammation, was a
disease of the respiratory system. However, an association between
OSAHS and cardiovascular involvement was also established.
Although the mechanisms underlying this association were not well
understood, it was shown that OSAHS altered endothelial function
by altering the regulation of endothelial vasomotion (Decreased
nitric oxide production at the vascular wall). us, measurement of
endothelial dysfunction is an early marker of cardiovascular damage
related to OSAHS.
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