Obstructive Sleep Apnea Syndrome: An Under -recognized Clinical Entity with Significant Systemic Morbidities

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RUHS Journal of Health Sciences, Volume 3 Number 1, January -March 2018
Review Article
Obstructive Sleep Apnea Syndrome: An
Under -recognized Clinical Entity with Significant
Systemic Morbidities
Ramakant Dixitl, Satyadeep Verma29 Jitendra Jalutharia3 and Anubhav Sharma4
Professor, 3 Resident, 4 Senior Resident, Department of Respiratory Medicine and Tuberculosis,
JLN Medical College and Associated Group of Hospitals, Ajmer, Rajasthan; 2 Senior Resident,
Department of Respiratory Medicine and Tuberculosis, RUHS College of Medical Sciences
and Associated Hospital, Jaipur, Rajasthan, India
ABSTRACT
Obstructive sleep apnea syndrome (OSAS) is a highly
prevalent yet under recognized sleep disorder,
characterized by repeated disruptions of breathing during
sleep. Not just merely a local phenomenon of upper
respiratory tract obstruction, this has many consequences
that includes intermittent hypoxia, intermittent
hypercapnia, reoxygenation, intra thoracic pressure
changes, sympathetic activation, micro -awakenings and
sleep fragmentation leading to metabolic dysregulation,
endothelial dysfunction, systemic inflammation,
oxidative stress, hypercoagulation, and neurohumoral
changes that causes excessive daytime sleepiness,
neurocognitive deterioration, endocrine, metabolic and
other systemic effects including poor quality of life. There
are increasing evidences to suggest that OSAS is a
systemic inflammatory disease. Epidemiological studies
have identified OSAS as an independent risk factor in
cardiovascular diseases, metabolic syndrome and
bronchial asthma. Patho-physiological changes in OSAS
are causally linked to the hypertension with increase risk
for heart failure, stroke and cardiovascular mortality. In
addition, OSAS is associated with several other disorders
and comorbidities that may affect almost every organ
systems of our body. Despite having many complex
systemic consequences, OSAS and its secondary effects
are mostly controllable by continuous positive air
pressure (CPAP). This disorder largely remains an
underestimated clinical entity due to unawareness by both
the patient and physician alike. There is need for
awareness regarding this entity among all specialties of
medicine and surgery as the so called undetected/occult
disease if remain untreated may lead to significant
systemic morbidities and at times mortality.
INTRODUCTION
Sleep is essential to life and to overall health. Most of us
need an adequate and quality sleep to function in a proper
manner. Lack of sleep can have profound consequences
on a daily routine and potentially long term basis for our
health and mental well being. Long term health
consequences related to lack of sleep could be high blood
pressure, diabetes, obesity and heart diseases that may
culminate to a shortened life expectancy. Most common
types of sleep disorders are sleep apnea, insomnia,
narcolepsy, restless leg syndrome, sleep paralysis etc.
Among all the sleep disorders, sleep apnea is most
common type of disorder. It is of three types- obstructive
sleep apnea, central sleep apnea and mixed sleep apnea.
Obstructive sleep apnea is most common among these
three and rather a complex syndrome called obstructive
sleep apnea syndrome (OSAS) in view of its wide clinical
manifestations and systemic consequences.
OSAS is a highly prevalent yet under -recognized clinical
problem. It is a potentially disabling condition
characterized by disruptive snoring, repeated episodes of
complete or partial pharyngeal obstruction during sleep,
marked swings in intra thoracic pressure and increased
sympathetic activities resulting in nocturnal hypoxemia,
frequent arousals, witnessed nocturnal interruptions and
excessive daytime sleepiness.' OSAS has become a
leading public health problem both in the developed and
developing nations. However, awareness regarding its
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RUHS Journal of Health Sciences, Volume 3 Number 1, January -March 2018
existence, diagnostic options, management and
consequences of untreated OSAS largely remains
inadequate. In developing countries, the burden is
enormous as resources for adequate sleep medicine
facilities for diagnosis are grossly lacking. Therefore,
there is always a need for low cost, simple and accurate
diagnostic and therapeutic modalities for true estimation
of disease burden and subsequent management.
In the Western world, the prevalence of OSAS is 3% to7%
in men and 2% to 5% in women.' In Indian scenario 2.4%
to 4.9% male and 1% to 2% female are affected by OSAS
as per data available from few centres.' Polysomnography
(PSG) is considered as gold standard for diagnosing sleep
disorders that essentially include either home based or in
hospital overnight recording and assessment of various
sleep parameters using Polysomnography. The severity of
OSAS is classified as mild, moderate and severe based
upon apnea-hypopnea index (AHI). The management
options of OSAS include behavior modification, sleep
position changes, weight control, continuous positive air
pressure (CPAP), oral appliances and surgery etc. The
CPAP remains the time trusted and most effective
measure among all.
There are enough evidences today to suggest that OSAS is
not a localized disorder rather it has several significant
systemic consequences that are usually underestimated
among the treating physician, pulmonologist,
cardiologist, surgeon, pediatricians, neurologist,
psychiatrist, endocrinologist and rather all other clinical
branches of medicine and surgery because patients
usually avoid to express the symptoms as they assume
them to be nothing unusual and treating physician also do
not ask specifically about them in routine practice. The
aim of writing this review is to create awareness among all
medical practitioners regarding this significant but
unfortunately under suspected clinical entity which at
present truly represent the tip of an iceberg.
PATHOPHYSIOLOGY OF OSAS
A variety of factors have been identified that are known to
contribute this condition and these include alteration in
the upper airway anatomy, neuromuscular function and
sleep -wake and ventilator control instability. The upper
airway in OSAS subjects, when compared with controls,
is smaller and narrowed laterally rather than in the antero-
posterior dimension due to increased thickness of the
muscular pharyngeal wall. Nasal obstruction due to either
mechanical (septal deviation, enlarged inferior turbinates
and nasal polyps) or inflammatory/ vasomotor (acute and
chronic rhinitis) causes has been proposed to contribute to
OSAS. The frequency of OSAS events may increase in
the supine compared with the lateral recumbent posture.
Oxygen desaturation may also worsen further in the
supine position. This positional variability of OSAS has
been attributed possibly to the effects of gravity on upper
airway size and shape.' Racial studies and chromosomal
mapping, familial studies and twin studies have provided
evidence for the possible link between the OSAS and
genetic factors also.6
RISK FACTORS OF OSAS
There are certain known and hidden risk factors that can
lead to development of OSAS, among them obesity is
most common and most prevalent. But it is also true that
OSAS is not uncommon in non obese individuals. Other
factor includes- old age, male gender, anatomical defect
like micrognathia, retrognathia, high arched palate,
macroglossia, nasal polyp, deviated nasal septum, genetic
predisposition, familial aggregation, cigarette smoking,
menopause, alcohol intake, night time nasal congestion,
endocrine abnormalities (hypothyroidism/acromegaly,
polycystic ovarian syndrome), Down's syndrome, drugs
like benzodiazepines, muscle relaxants, testosterone
therapy7'8 etc.
Recently bronchial asthma, chronic obstructive
pulmonary disease (COPD), metabolic syndrome, certain
psychiatric problems etc has also emerged as important
risk factors for development of OSAS. Poor control of
these disorders has been consistently associated with poor
sleep, restlessness, breathlessness and poor quality of life
among these patients.
OSAS and Respiratory disorders:
It is primarily a sleep related respiratory disorder where
the primary event is sleep -related collapse of the pharynx
in the face of persistent ineffective breathing efforts.
Repetitive collapse of the upper airway during sleep leads
to ineffective sleep and day time sleepiness. The
symptoms are therefore related to (i) sleep i.e.
unrefreshing sleep, unrestorative sleep, disturbing
snoring, breathing pauses, restless sleep, nocturia,
nocturnal sweating, gasping sounds, wake-up suffocating
(ii) wakefulness i.e. tiredness, lack of energy, sleepiness,
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RUHS Journal of Health Sciences, Volume 3 Number 1, January -March 2018
memory impairment, anxiety and irritability, depression,
lack (or loss) of interest, sexual dysfunction (erectile
dysfunction, loss of sexual desire), headaches etc.
Most common respiratory disorders that are now linked
with OSAS are COPD and bronchial asthma, and this
association is also known as 'Overlap' and 'Alternate
overlap syndrome', respectively. There is a positive
association between OSAS and occasional wheezing,
persistent wheezing, snoring, and a history of asthma.
There are several mechanisms for how asthma may
worsen OSAS and, conversely, how OSAS may
complicate asthma.' Asthmatics have disrupted sleep
architecture as a result of frequent arousals from sleep,
decreases in sleep efficiency, and variable effects on sleep
stage distribution when compared to healthy controls.
There are certain factors that are responsible for increased
prevalence of OSAS among asthma patients and these
includes allergic rhinitis, oral and inhaled corticosteroid,
gastro-eosophageal reflex disease (GERD), beta -2
receptor down regulation, decreased inspiratory muscle
activity and neurohormonal changes' etc. Prevalence of
OSAS among asthma patients ranges from 27% to 60%
world- wide."'" A high OSA risk of 39% was found in
asthma patients by Auckley et al12 and Alkhalil et al" also
found high prevalence of OSA in asthma group compared
to control group (60% v/s 17%). A cohort study observed
high risk of OSA in asthma patients compared to general
population (12.1 v/s 4.84 per 1000 person-year).14
Overlap patients (OSAS with COPD) presents with more
nocturnal desaturation and pulmonary hypertension than
patients with either OSAS or COPD alone. These patients
had a higher breathing frequency, lower tidal volume,
lower FEV1 and FVC, poor ventilatory response and
reduction in respiratory drive than OSAS alone patients."
COPD has been linked with skeletal -muscle myopathy
and it may be that COPD (or cigarette smoking) affects the
upper -airway dilator muscles or reflexes. The most
significant sleep abnormality associated with COPD is
nocturnal oxygen desaturation. Even without any upper -
airway abnormality, 27% to 70% of patients with COPD
with oxygen saturation of 90% to 95% at room air
experience substantial desaturation during night and
particularly in REM phase of sleep." In addition to
increased morbidity and mortality, patients with the
overlap syndrome also have significantly worse quality of
life when compared to 'COPD only' controls.
The prevalence of OSAS is known to be increasing in
patient having idiopathic pulmonary fibrosis (IPF),
therefore the most recent IPF guidelines recognize OSAS
as an important associated comorbidity that can influence
patient survival in these patients!' Sleep is found to be
markedly disturbed in several studies among IPF patients.
Common abnormalities recognized are atypical sleep
macro and micro architecture (increase stage 1 sleep,
decrease REM, decrease sleep efficiency, increase arousal
index etc), respiratory breathing pattern, oxygen
desaturation and features of hypoventilation. The role of
underlying OSAS in general health status of IPF patients
has now been recognized in several studies. Some features
of OSAS such as increased gastro esophageal reflux,
exaggerated intra thoracic mechanical strain, and
intermittent hypoxia with oxidative stress may impact
progression of IPF. The associated cardiovascular and
cerebrovascular morbidity seen in OSAS patient may turn
IPF patients towards life threatening situation. The
current recommendation favors immediate referral of IPF
patient to exclude associated comorbidities such as OSAS
and in high risk patient not only for better management
strategy in such patient but inclusion in clinical trials and
research as well."
OSAS and Cardiovascular disorders:
Cardiovascular comorbidities are commonly and most
frequently associated with OSAS. OSAS is an
independent risk factor for the development of several
cardiovascular consequences. The mechanisms involved
in this association are rather complex and diverse. Patients
with OSAS experience repetitive episodes of
deoxygenation and reoxygenation during transient
cessation of breathing that may provoke systemic effects.
Alternate hypoxia and reoxygenation leads to endothelial
dysfunction, oxidative stress and increased sympathetic
activity during sleep. Levels of nitric oxide, a major
vasodilator substance released by the endothelium, have
been found to be decreased in OSAS patients!' Several
studies have reported higher level of a potent
vasoconstrictor i.e. endothelin-1 in OSAS patients.2°
Clinic -based studies have also suggested that OSAS is
associated with impaired brachial artery flow -mediated
dilation and endothelial -mediated vasodilatation
impairment.21
The largest epidemiological community -based study of
OSAS and cardiovascular disease was the Sleep Heart
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RUHS Journal of Health Sciences, Volume 3 Number 1, January -March 2018
Health Study, conducted on 6424 subjects across the
USA. This study found that apnea-hypopnea index (AHI)
>11/hour was associated with 1.42 fold higher risk of
development of any cardio vascular co morbidity as
compare to AHI < 1.4/hour.22 OSAS may contribute to left
ventricular failure, systemic hypertension, pulmonary
hypertension, stroke and cardiac arrhythmias.
Sympathetic discharge, mechanical stress on the
myocardium from the intra thoracic pressure changes are
potentially arrhythmogenic. Brady-arrhythmias are
commonly encountered in OSAS and may correlate with
the severity of disordered breathing. A prospective study
demonstrated that the recurrence of atrial fibrillation at 12
months following successful cardioversion was halved
for those treated for OSAS compared with untreated
OSAS."
Observational studies have shown that hypertension and
OSA often coexist and subjects with OSA tend to have
higher blood pressure (BP) than matched controls.
Longitudinal studies from the Wisconsin Sleep Cohort,
which provides prospective evidence also implicates OSA
as a possible causal factor in hypertension.24 Several
studies have investigated the association between stroke
and sleep -disordered breathing. Reports from two
observational cohorts showed moderate to severe sleep -
disordered breathing as risk factor for prevalent stroke
and, with serial polysomnographic data, demonstrated
that the preexisting sleep disorder may be a risk factor for
incident stroke." Recently, there is increasing interest in
the role of OSA treatment on outcomes in heart failure
also.
A link between OSAS and peripheral artery disease (PAD)
is also recognized. OSAS is known to be associated with
several biologic pathways or development of
atherosclerosis such as inflammation, systemic
hypertension, endothelial dysfunction and insulin
resistance. A multiethnic study of atherosclerosis (MESA)
assessed association between OSAS and peripheral artery
disease on 4,000 patients. Higher prevalence of PAD was
observed in African American patient's compare to other
ethnic groups. In longitudinal analysis; self reported
OSAS was associated with two fold increase in newly
diagnosed PAD measured by ankle brachial index.26
Therefore, one should recognize the risk of this
association while dealing such patients.
OSAS and Cognition:
OSAS is associated with impairment of cognition,
emotional state, and quality of life. The effects are most
apparent in the severe cases. Reported impairments
include global intellectual dysfunction and deficits in
vigilance, alertness, concentration, short and long-term
memory, and executive and motor function. Clinical
studies suggest that OSAS impairs the structural integrity
of several brain regions, including the medial temporal
lobe. OSAS and hypertension trigger hypo perfusion and
hypo metabolism at certain cerebral regions. OSAS
promotes hippocampal atrophy, which is associated with
memory impairment." A study done over 10 years found
that patients with spontaneous CSF leak were associated
with high rate of OSAS and hypertension." There are
certain mechanisms that explain the impaired cognition
among OSAS patients. Excessive daytime sleepiness
increases the risk for impairment in multiple domains of
cognition.29 Another possible hypothesis includes
intermittent hypoxemia, sleep fragmentation and
disturbed circadian rhythm."
OSAS and Epilepsy:
Sleep disordered breathing (SDB) seems to be correlated
with seizure disorders. Seven out of 11 subjects with
incomplete seizure control were found to have mild to
severe OSAS in a study." Multiple mechanisms may
account for the higher than expected co -occurrence of
epilepsy and SDB. OSAS may hinder the control of
epilepsy through sleep disruption or repetitive
hypoxemia. Generalized or focal seizures can induce
central as well as obstructive apneas during the ictus.32 A
common hypothesis underlying seizures, reduced central
respiratory drive and even depression, may be represented
by a dysfunction of serotonin pathways in the central
nervous system. This could also have important
implications for the sudden unexpected death in
epilepsy." Some observational studies have suggested
improvement of seizure control following SDB treatment
by CPAP.
OSAS and Neuromuscular disorders:
Sleep -disordered breathing in neuromuscular disorders is
due to an exaggerated reduction in lung volumes during
supine sleep and specific features of the diseases that may
promote upper airway collapse. Diaphragm palsy, spinal
cord trauma, post polio syndrome, myasthenia gravis etc
leads to obstructive as well as central sleep apnea.
Decrease in the rib cage during REM sleep resulting in
saw -tooth oxygen denaturation possibly represents the
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RUHS Journal of Health Sciences, Volume 3 Number 1, January -March 2018
earliest manifestation of respiratory muscle weakness.
Hypoventilation can occur in REM sleep and progress
into non -REM sleep, with continuous desaturation and
hypercarbia. Specific characteristics of neuromuscular
disorders, such as pharyngeal neuropathy or weakness,
macroglossia, bulbar manifestations, or low lung
volumes, predispose patients to the development of
obstructive events.34
OSAS and Metabolic syndrome/ endocrine disorders:
Metabolic syndrome is an emerging public health
problem characterized by hypertension, insulin
resistance, dyslipidemia and obesity. Metabolic syndrome
with cluster of cardiovascular risk factors is also
associated with obstructive sleep apnea. Its prevalence
varies from 74% to 85% among patients with OSAS. The
metabolic syndrome is featured by a prothrombotic state
with increased plasminogen activator inhibitor -1,
fibrinogen and C -reactive protein (CRP). A number of
epidemiological studies have found links between OSAS
and metabolic syndrome. Obese OSAS patients may have
an increased rate of metabolic syndrome and higher levels
of serum lipids, fasting glucose, leptin, and fibrinogen
than obese subjects without OSAS." Both OSAS and
metabolic syndrome may exert negative synergistic
effects on the cardiovascular system through multiple
mechanisms. Many studies have shown that treatment of
OSAS leads to improvement in hypertension and
cholesterol level." Therefore, clinicians need to be
encouraged to systematically evaluate the presence of
metabolic abnormalities in OSAS and vice versa.
Some autoimmune diseases such as Hashimoto's
thyroiditis are also linked with OSAS even if they are
euthyroid. The mechanism proposed to explain this
relationship are mucoprotien deposition in upper airway,
decreased neural output to upper airway musculature,
obesity and abnormal ventilator control etc.37
OSAS and Depression:
There is increasing prevalence of depression in OSAS
patients that varies from 17% to 58%. Many patients with
OSAS are diagnosed to be having a depressive disorder
and many receive antidepressant medications before they
are actually referred for assessment for sleep disorder.
Several studies attempted to delineate the relationship
between depression and components of OSAS. One study
found that 56.7% of OSAS patients had depressive
symptoms and among them 21.6% had moderate to severe
symptoms." Most common cause of depression in OSAS
is sleep fragmentation and hypoxia. In some cases,
treatment of comorbid insomnia and anxiety with a
benzodiazepine and hypnotics may actually worsen
OSAS. These medications may decrease muscle tone in
the already functionally impaired upper airway dilator
muscles, blunt the arousal response to hypoxia and
hypercapnea, and increases the arousal threshold for the
apneic event, therefore increasing the number and
duration of apneas." Another study found that patients
with treatment resistant depression with comorbid OSAS
got improvement in mood and cognition after two month
of CPAP therapy.°
OSAS and Sexual life:
Snoring is estimated to be the third most common cause of
divorce in the United States and Great Britain. OSAS can
cause erectile dysfunction (ED) in men and loss of libido
in women. There are several mechanisms by which sleep
apnea could cause ED, such as sleep fragmentation that
reduces spontaneous erections at night, hormonal
impairment (testosterone hormone level increase with
sleep) or endothelial dysfunction. Depression is one of
the important causes for decrease libido.41 On the other
hand, oxidative stress affect hypothalamic -pituitary
complex and lead to psychological depression and
decreased libido. A study on 90 patients evaluated
relationship between OSAS by PSG and ED by
questionnaire and it was found that patients with OSAS
were linked with low ED score and showed significantly
improvement after CPAP therapy.42
OSAS has now been recognized as an important
underlying pathogenic factor for sexual dysfunction.
There is strong evidence to suggest that OSAS
independently causes endothelial dysfunction which is
link with ED. ED patients treated with CPAP has shown
positive improvement after three months in few studies!'
OSAS is also linked with female sexual dysfunction
irrespective of severity of OSAS. OSAS in female
corresponds with pre and post menopausal women. Post
menopausal women diagnose to have polycystic ovary
syndrome (PCOS) that is characterized by high androgen
level and low estrogen level is also linked with OSAS.
PCOS is usually accompanied by certain characteristics
such as insulin resistance, glucose intolerance, and type -2
diabetes, which can be linked to the onset of OSA.°
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RUHS Journal of Health Sciences, Volume 3 Number 1, January -March 2018
OSAS and Renal disorders:
A high percentage of OSAS patients suffer from urinary
symptoms such as frequency, nocturia, enuresis and
overactive bladder etc. There is also high risk for chronic
kidney disease in patient having severe OSAS without
hypertension and diabetes. End stage renal disease
(ESRD) is believed to increase OSAS severity by
mechanism such as fluid overload causing congestive
cardiac failure. ESRD may also contribute to
pathogenesis of OSAS. ° Intermittent hypoxia in OSAS
patient results in oxidative stress that can cause alteration
in bladder, detrusor instability and spontaneous
contraction. Patient of benign prostate enlargement who
frequently awake during sleep may have possible OSAS
component. Severe OSAS has also been link with
overactive bladder, urgency incontinence and nocturnal
urination and altered bladder function in several studies.°
Both obstructive and central sleep apneas are not
uncommon and equally distributed in patients of renal
failure. Upto 80% of chronic dialysis patients complain of
sleep disturbances and reduced daytime alertness. Most
common cause of this condition is insulin resistance and
atherosclerosis. Intermittent hypoxia and sympathetic
activity also contribute it. In healthy young subjects,
restricting time in bed to four hour per night for six days
induces alterations in metabolic and endocrine function,
including increased sympathetic tone and a state of insulin
resistance.46 Both abnormalities are well known
complications of chronic uremia. There are few valid
studies documenting the occurrence of sleep apnea among
dialysis patients. As sleep apnea is common in renal
failure, the nephrologists must have a high degree of
suspicion in patients complaining of the symptoms or
presenting with signs and symptoms suggestive of sleep
apnea. A study conducted on 254 patients with renal
disease, sleep apnea was found in 57% hemodialysis
patients of ESRD.°
OSAS and Liver disorders:
OSAS is also possibly associated with non alcoholic fatty
liver disease and liver fibrosis. Several studies have
suggested the impact of OSAS on liver function. A study
in patients with fatty liver disease and altered liver
function found A111 >5 in 50% and further 20% among
them were having severe OSAS.° Chronic intermittent
hypoxia (mimicking the oxygen profile of patients with
severe OSAS) in mice on a high fat diet has been
demonstrated to induce progression of hepatic steatosis to
liver fibrosis and worsened hepatocellular injury.
Hypoxia inducible factor -1 and over expression of lipo
oxygenase has been linked with liver fibrosis in OSAS
patients 49
OSAS and Ocular manifestations:
A growing body of literature shows a relationship between
OSA and various ocular problems, however; the possible
link between OSA and ocular manifestations are mostly
depending on the observational and case series. Ocular
associations of OSAS have been an issue of great interest
in view of the irreversible complications it may cause and
may have been preventable, if the OSAS is diagnosed and
managed effectively beforehand or even after the
diagnosis of the ocular findings. Ocular manifestations
associated with OSAS are floppy eyelid syndrome,
glaucoma, papilledema, retinal vein occlusion and non-
arteritic anterior ischemic optic neuropathy, cornea
disorders (keratoconus), central serous chorioretinopathy
etc. Those who had been diagnosed with OSAS were 1.67
times more likely to have open angle glaucoma in the five
years after their diagnosis than those without sleep
disorder in one study. Treatment of OSAS has been shown
to be effective in controlling the risk of glaucoma.' There
is a need for prospective randomized clinical trials and
experimental studies to explain the underlying
mechanisms of the associations between OSA and the
related ocular pathologies.
OSAS and Rheumatic disorders:
Sleep abnormalities have been recognized in several
rheumatic diseases including rheumatoid arthritis,
osteoarthritis, systemic lupus erythematosis, systemic
sclerosis, scleroderma, sarcodosis, behcet's syndrome etc.
A large population study found 50% of rheumatoid
arthritis patients having high risk for sleep apnea on
standard questionnaire. OSAS in rheumatic patient may
contribute to increase pain and fatigue perception.
Untreated OSAS with intermittent hypoxia is associated
with increase level of systemic inflammatory markers
such as CRP and pro inflammatory cytokines.51 However,
the impact of OSAS as comorbidity in rheumatic patients
to the extent and response to therapy of inflammatory
rheumatic disease is currently unknown.
OSAS and Dental disorders:
Many studies have shown greater prevalence of
periodontitis in patients with diabetes, cardiovascular
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RUHS Journal of Health Sciences, Volume 3 Number 1, January -March 2018
disease, rheumatoid arthritis, and osteoporosis.
Research indicates that patients with sleep apnea have
increased plasma markers of systemic inflammation and
increased levels of circulating cytokines in obesity. It is
hypothesized that OSAS may be linked to increased risk
of periodontal disease because of its association with an
elevated inflammatory response.52 A cross-sectional
study on 687 subjects concluded that 17.5% of subjects
had periodontitis, 46.6% had OSAS and 60% of those
diagnosed with periodontitis also had OSAS. 53
OSAS and Skin disorders:
Few studies have investigated a possible relationship
between OSAS and dermatologic illnesses i.e.
psoariasis, a chronic immune mediated inflammatory
skin disease that is thought to be associated with OSAS,
metabolic syndrome and cardiovascular disease. The
link between OSAS and psoriasis is complex and
possibly mediated by systemic inflammation.54 Few
reports have also investigated the association between
OSAS and atopic dermatitis. A retrospective cohort
study from Taiwan with over 5.5 year follow up,
investigated the relationship between OSAS and risk of
atopic dermatitis. The incident rate for atopic dermatitis
in patient with OSAS was 9.81 per 1000 person -years.
The incidence was 1.5 times higher in patient with
OSAS then age and gender matched comparison group.
The risk was more pronounced in younger age group and
in men.55 Further, studies are required to explore the
underlying mechanism in this relationship.
OSAS and ICU care:
Sleep related breathing disorders are not uncommon in
critical ill as well as in post operative patients because of
anatomical reason there is increase risk of difficulty in
endotracheal intubation. OSAS patients undergoing
surgery are at more risk of post operative complications.
Therefore high post operative transfer to ICU and
increased stay in ICU is expected in OSAS patients.
Minimal use of sedative and opioid as well as liberal use
of CPAP is recommended in patients who have OSAS or
having high risk of OSAS. There are several thumb rules
to be remembered by critical care physician such as
desaturation and apnea may not always be a part of
respiratory failure, early positive airway pressure can be
applied to prevent reintubation and extubation to be
performed in lateral or semi upright position without use
of sedatives. Regional anesthesia for surgery is better
alternative in patient having OSAS.56
OSAS in Children:
Obstructive sleep disordered breathing is not uncommon
in children. From 3 % to 12 % of children snore, while
obstructive sleep apnea syndrome affects 1 % to 10 % of
children. The majority of these children have mild
symptoms, and many outgrow the condition.
Consequences of untreated obstructive sleep apnea
include failure to thrive, enuresis, attention deficit
disorder, behavior problems, poor academic
performance, endocrine, metabolic and cardiopulmonary
disease. The most common etiology of obstructive sleep
apnea in children is adenotonsillar hypertrophy and loss
of neuro muscular tone. Snoring and mouth breathing
often prompt parents to seek medical attention for their
children. Septal deviation, choanal atresia, nasolacrimal
cysts, and nasal aperture stenosis must be considered in
infants. In older children, nasal polyps and turbinate
hypertrophy must be ruled out. In children (lto12 years),
an apnea-hypopnea index greater than 1 (average: 0.1 to
0.5 events per hour) or a minimum oxygen saturation of
less than 92% (average: 96% ± 2%) is considered
abnormal. Adenotonsillectomy, a routine procedure, has
been shown to improve snoring, OSAS, weight
problems, enuresis, and behavior problems in children
who have the entire clinical spectrum of sleep disordered
breathing. CPAP is the treatment of choice when
adenotonsillectomy is contraindicated or has failed.
Children with craniofacial syndromes, neuromuscular
diseases, medical comorbidities, or severe obstructive
sleep apnea, and those younger than three years are at
increased risk of developing postoperative complications and
should be monitored overnight in the hospita1.57
OSAS and Cancer:
Obstructive sleep apnea (OSA) has been associated with
increased cancer mortality and cancer incidence. OSA
has been recognized as an oxidative stress disorder.
Chronic and intermittent hypoxia along with reactive
oxidative stimuli can activate transcription factors, such
as hypoxia inducible factor -1 which are known to play a
key role in regulating the various stages of tumor
formation and progression. Sleep apnea related hypoxia
may also increase the susceptibility to develop a new
cancer. Increased overnight hypoxia as a surrogate of
OSA severity was associated with increased cancer
incidence in a multicenter, clinical cohort study between
year 2003 and year 2007 at seven Spanish teaching
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RUHS Journal of Health Sciences, Volume 3 Number 1, January -March 2018
hospitals. The findings of this study showed that OSA
severity was independently associated with increased risk
of incident cancer especially among male and in patients
younger than 65 years of age.58
OSAS and Road traffic accidents:
It is widely assumed that the risk of automobile accidents
is increased in patients with sleep apnea syndrome
particularly in those with severe disease. Howard et
arestimated that 50% among 3000 commercial drivers
were at risk for sleep apnea. Assessment of the risk of
OSAS and development of effective methods to identify
and treat commercial drivers with OSAS is an important
part of the mission of the certain motor carrier safety
department in western countries. A study 60 with 60 control
and 60 cases of OSAS in motor drivers found that
prevalence of at least one accident in last three years were
higher in case group (33%) than control group (18%).
Patients with sleep apnea, as confirmed by PSG had a
greater probability of having a traffic accident than
patients without sleep apnea. Drivers with an AHI above
15 were significantly more likely to have multiple
accidents in a period of five years than drivers with AHI of
less than five.61
OSAS and Occupational hazards:
Although, OSAS is a non -occupational disease, its
frequency, comorbidities, and potential to impair
performance, makes it an important determinant to the
health and safety at the workplace. OSAS mostly remains
undiagnosed in general population and at the work place
as well and thus, remains untreated. Excessive daytime
sleepiness related to OSAS has been repeatedly
implicated in major transport accidents. OSAS has also
been demonstrated to have adverse impacts on
employees, healthcare costs and workplace productivity.62
Results from 27 observational studies (n=268,332),
suggest that workers with sleep problems had a 1.62 times
higher risk of being injured than workers without sleep
problems. Approximately 13% of work injuries could be
attributed to sleep problems.63
OSAS and Cellular phones:
Cellular phone has become an integral part of our daily
life. It's very difficult for today's youth to live a single day
without using this technology as there is irresistible desire
for its use. Use of mobile phones during late night can
have profound effects on sleep, resulting in fragmented
sleep and decreased grade point average, alertness,
impaired concentration, depression, anxiety etc. It has
been reported that about 25% to 47% of college students
experience disruptions in sleep due to cellular phones."
OSAS is becoming more prevalent in younger
populations and is commonly under diagnosed in college
aged students. In a sample of over 1,845 college students,
over 500 students were at risk for at least one sleep
disorder, with OSAS being the commonest one.65 In a
sample of 60 college students, findings revealed that
students who attended to technology after sleep onset
reported increased sleep disruption and daytime
impairment as compared to non -technology users.66
CONCLUSION
Within depth review of the systemic manifestations or
associations of OSAS; authors of this paper stress on high
degree of suspicion and the attention among all medical
persons whether general physician, cardiologist, pulmonologist,
surgeon, dentist, psychiatrist, neurologist, dietician,
endocrinologist, pediatrician, otorhinolaryngologist, critical
care and intensivist, nephrologists, hepatologist,
ophthalmologists etc towards the OSAS as this is an
important, yet under diagnosed but treatable disorder.
Initially this disorder was linked to only few sleep
disturbances but huge literatures now available prove that
OSAS is widely connected in human body. It can affect
major organs to minute capillaries, old person to neonate
and even young and active teenage, a simple home
resident people to active workplace person, non obese
person to obese person and therefore represents a truly
complex syndrome. Therefore, treating physician should
always try to assess the sleeping pattern and behavior in
patients with even slightest doubt of OSAS. Several
studies have proved that treatment of OSAS by CPAP
significantly improves not only the sleeping problem but
also the associated comorbid illness.
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Corresponding Author
Dr Ramakant Dixit, A-60, Chandravardai Nagar, Ajmer.
Rajasthan, India.
e-mail : dr.ramakantdixit@gmail.com
Miscellanea
Campus News
WORKSHOP
Rajasthan University of Health Sciences conducted three
days workshop on "Research Methodology - Basics of
Biostatistics Workshop" from 96 to 11th February 2018.
Eminent speakers like Dr N C Jain, Scientist G, ICMR,
New Delhi; Dr Shreenivas, Professor, Biostatistics,
AIIIVIS, Delhi; Dr Mario Vaz, Professor, Physiology, St
John's Medical College, Bangaluru; Dr Tulsi Adhikari,
Scientist -E, NIMS, ICMR, New Delhi; Dr Atul Juneja,
Scientist -D, NIMS, ICMR, New Delhi and Dr V M
Katoch, ICMR-NASI Chair at Rajasthan University of
Health Sciences, Jaipur conducted the workshop. The
workshop comprised of sessions on biostatistics, problem
identification and formulation of research
question/hypothesis, review of literature in developing
research proposals, concept of sampling, data
management, hypothesis testing, sample size calculation,
representation of data, correlation and regression
analysis. Hands on training was given to the participants
on sampling, descriptive analysis and regression analysis.
Workshop was attended by 55 participants from all over
the state. Rajasthan Medical Council accredited 6 credit
hours.
CME PROGRAMMS
A guest lecture on 9th February 2018 on "Basic Research
Methodology" was delivered at Rajasthan University of
Health Sciences, Jaipur by Dr Mario Vaz, Professor, St
John's Medical College, Bengaluru.
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