Management of obstructive sleep apnoea syndrome

THERAPY FOCUS ■ Management of obstructive sleep apnoea syndrome PRASHANTHI RATNAKUMAR AND ARI MANUEL O bstructive sleep apnoea (OSA) is already a s...
Author: Jemimah Quinn
4 downloads 0 Views 229KB Size
THERAPY FOCUS ■

Management of obstructive sleep apnoea syndrome PRASHANTHI RATNAKUMAR AND ARI MANUEL

O

bstructive sleep apnoea (OSA) is already a staunch contributor to the national burden of respiratory disease and this burden is growing rapidly. Healthcare professionals are now increasingly aware of presenting symptoms such as snoring, ‘choking’ episodes during sleep and excessive daytime somnolence. When excessive daytime sleepiness is present, the condition is referred to as obstructive sleep apnoea syndrome (OSAS). This review explores current knowledge regarding the epidemiology, pathogenesis, diagnosis and treatment of OSAS, as well as looking in more detail at the links between OSAS and other common co-morbidities – an area of growing research interest that may provide alternative targets for therapeutic intervention.

Epidemiology Although OSAS was first described in the 1970s, epidemiological figures are a relatively recent work in progress, only prescriber.co.uk

SPL

Obstructive sleep apnoea (OSA) describes the pathological narrowing and collapse of the upper airway in recurrent episodes during sleep. This can result in a variety of symptoms that markedly affect quality of life. In addition, other chronic complications, most significantly the development of long-term cardiovascular disease, are increasingly becoming recognised.

stretching back over the last 15 to 20 years. Estimates of prevalence vary, most likely due to a combination of differences in methodological assessment. Ideally, diagnosis of OSAS requires poly­ somnography conducted during an overnight sleep study; a time-consuming and expensive measure with limited patient compliance. At present, OSA is thought to affect approximately 10–17 per cent of men and 3–9 per cent of women aged 30–70 years.1 These figures are primarily based on data from the Wisconsin Sleep Cohort, a prospective community-based study ongoing since 1988, which has used relatively rigorous methods of polysomnography and ongoing assessment to follow its study population. However, although current UK guidance uses these estimates,2 more recently, the HypnoLaus study conducted in Switzerland 3 surveyed over 2000 individuals and recorded prevalences of 49·7 per cent in men and 23·4 per cent in women. It is also important to recognise that there is likely to be a high prevalence of patients with undiagnosed Prescriber August 2016 ❚ 23

■ THERAPY FOCUS l Obstructive sleep apnoea

Increasing age Male gender Obesity (BMI >30) Asian ethnicity First-degree relatives with OSAS Craniofacial anatomy, eg tonsillar hypertrophy, retrognathia • Possible associations with smoking and increased alcohol intake • Possible associations with asthma13

sympathetic nervous activity to increase respirator y drive, which eventually restores breathing patterns and re­opens the airways.4 In patients with OSAS, this can occur many times a night, and the intermittent cycles of hypoxaemia and periodic states of arousal play a key role in driving many of the co-morbidities associated with OSAS.

Table 1. Risk factors for the development of obstructive sleep apnoea syndrome (OSAS)12

Classically, risk factors for the development of OSAS include age, male gender and obesity. Of these, obesity is certainly one of the most commonly highlighted risk factors, as well as one of the most modifiable. Obesity can result in biomechanical imbalances due to the increase in adipose tissue exerting extraluminal pressure on the pharynx, causing a pressure imbalance, as described above. Numerous studies have shown that obesity, and particularly neck circumference, are independent predictors of OSAS. Weight gain can increase the severity of OSAS; conversely, weight loss can moderately decrease severity.7-9 The association with obesity is also more pronounced in men than in women. Studies consistently demonstrate a higher prevalence of OSAS in men compared with women, and suggest that in women, OSAS severity is linked to a higher degree of obesity than the corresponding severity in men. Various mechanisms have been postulated to explain this, including different distributions of fat deposition in men and women,10 and hormonal influences related to testosterone levels (it is notable that OSAS in women is more commonly found postmenopause).9 One of the largest cohort studies conducted in Pennsylvania demonstrated a notable increase in the prevalence of OSAS with increasing age, quoted as being two to three times greater in the 65-year-plus age group compared with those aged 30–64 years. This may be a consequence of age-related increases in fat deposition, particularly around the pharynx, as well as changes in the structure and elasticity of the pharyngeal muscles with time.11 In addition to age, sex and weight, many other risk factors have now been

• • • • • •

OSA who do not present to healthcare professionals.

Pathogenesis The underlying pathogenesis of OSA is multifactorial. In normal physiology, the nasal passages and hard palate at the upper end of the pharynx have bony and cartilaginous foundations, providing a relatively fixed diameter for airflow. At the lower boundary, the trachea is structured in a similar fashion. The portion of the airway between these two regions is highly dependent on pharyngeal muscle activity and tone, as well as the balance of intraluminal against extraluminal pressure. Ordinarily, this flexibility is key to the pharynx’s role in complex actions such as speech and swallowing. However, where the pressure outside the pharynx (extraluminal) is greater than the intraluminal pressure, the airway narrows or collapses. During wakefulness, our conscious neuromuscular control assists with overcoming this; however, during deep sleep, the loss of conscious control facilitates varying degrees of obstruction, and subsequent hypopnoea or apnoea. This finding in association with OSA was first characterised in 1978 by Remmers et al. 4 Additional factors contributing to airway collapse have been widely studied since, including the concept that anatomically narrower airways may be more prone to collapse5 and the role of instability of ventilatory feedback systems, which respond to low oxygenation and raised carbon dioxide to resolve obstruction.6 As the upper airway obstructs, hypercapnia develops as gas exchange is impeded. The brainstem senses this, triggering a state of arousal via a surge in 24 ❚ Prescriber August 2016

Risk factors

identified. Differences in craniofacial anatomy, such as maxillary and mandibular lengths, as well as characteristics such as enlarged tonsillar tissue are recognised as mechanical contributors. Ethnicity is thought to play a role; although many of the studies on OSAS have been carried out on North American or European populations with a large Caucasian component, there is now more data emerging suggesting that patients of Asian origin have higher rates of OSAS for a given level of obesity, which may relate to possible differences in craniofacial anatomy. In addition, familial predisposition and genetics are increasingly recognised as important factors, with a higher risk in first-degree relatives. Table 1 summarises the key risk factors involved in the development of OSAS.

Recognition Patients who may be suffering from OSAS commonly present with symptoms associated with fragmented sleep and repeated arousals, as a result of recurrent airway obstruction. Table 2 summarises the common presenting symptoms. Excessive daytime sleepiness is a cardinal feature, although not always part of the initial presentation. Determining the degree to which daytime sleepiness occurs, and its impact on both quality of life and safety, eg when driving or at work, is extremely important, and can help guide decisions regarding treatment. Often, patients present in conjunction with partners or other family members, • Snoring •S  leep fragmentation – waking frequently throughout the night •E  xcessive daytime sleepiness: falling asleep during conversation or meals, or during periods of low activity, eg sitting in traffic • F eeling unrefreshed on waking •P  oor concentration during the day, irritability, mood swings •E  arly morning headaches – due to increasing hypercapnia overnight •N  octuria or nocturnal sweating •D  ecreased libido Table 2. Symptoms of obstructive sleep apnoea syndrome (OSAS) prescriber.co.uk

Obstructive sleep apnoea

who have noticed heavy snoring with characteristic pauses, followed by a gasp or choking sound as an arousal state triggers reopening of the obstructed airway. For this reason, collateral histories are often very useful. The role of GPs and community health professionals in eliciting such histories and considering a diagnosis of OSAS is therefore invaluable. Differential diagnoses to consider are listed in Table 3, as well as being summarised in the 2015 NICE guidance. 14 The NICE guidance also provides a helpful summary of ‘red flag’ symptoms; the most concerning differential diagnosis is that of upper airway obstruction secondary to an upper airway malignancy. Features such as recurrent epistaxis, change in voice or swallowing, or increasing severity of symptoms that are not accompanied by concomitant weight gain should be treated with more suspicion. Fur ther assessment of possible OSAS includes physical examination, looking particularly at parameters such as BMI, neck circumference and features of craniofacial anatomy, for example enlarged tonsils. Basic biochemical tests, including thyroid function tests, should also be carried out. Using written tools to help evaluate the severity of symptoms, such as the Epworth Sleepiness Scale (ESS) score or the STOPBang questionnaire, is also extremely useful in quantifying the impact on life. The ESS is a well-validated scoring system, with a specificity quoted at 80 per cent in detecting excessive daytime sleepiness (defined as a score of greater than 10/24 on the questionnaire).15 In addition, enquiring about any problems with sleepiness while driving, operating heavy machinery or during occupational responsibilities is important for patient and public safety. It may be necessary to discuss the involvement of employers or the DVLA where safety is at risk. Urgent referral for assessment may be necessary, warning patients not to drive or undertake high-risk jobs, eg operating heavy machinery, until they have been assessed and symptoms are adequately controlled with treatment (see Table 4). prescriber.co.uk

l THERAPY FOCUS ■

Narcolepsy Associated with vivid dreams, temporary paralysis on awakening Restless legs syndrome Causing periodic movements of the legs, which can result in arousal and awakening Hypothyroidism Symptoms can include excessive daytime sleepiness and lethargy Psychological causes of poor sleep Anxiety, depression and panic attacks can all result in poor sleep and intermittent awakening during the night Poor sleep hygiene Including factors such as irregular sleeping times, shift work patterns, use of caffeine, alcohol or other stimulants prior to bedtime Heart failure Can result in nocturnal gasping and difficulty breathing while lying flat Drug-related sleep disturbance Particularly with sedative or psychotropic medications Table 3. Key differential diagnoses of obstructive sleep apnoea syndrome (OSAS)

Diagnosis Where OSAS is suspected, patients should be referred for assessment in a sleep medicine unit with overnight sleep studies using polysomnography, if available. This consists of a series of measurements to assess various physiological parameters such as oxygenation, thoracic wall movement, airflow and breathing patterns. Ideally, this is conducted in an overnight sleep centre with trained technicians, but there is now increasing use of overnight polysomno­graphy assessment at home, which can provide sufficient information to diagnose OSA with considerably less logistical inconvenience to patients. Diagnosis is based on the number of apnoea/hypopnoea events per hour, creating an apnoea-hypopnoea index (AHI) figure. Under five events per hour is considered normal, with AHI scores of 5–14, 15–29, and greater than 30 being graded mild, moderate and severe OSA respectively. When polysomnography is not available, alternative diagnostic studies utilising respiratory variables (limited sleep study) or oximetry may be helpful in supporting the diagnosis

Treatment In mild sleep apnoea, lifestyle considerations should be addressed as part of man-

agement. Weight loss, aiming for a BMI of less than 25, is recommended. Other therapies should ideally be considered alongside this, as there is evidence to suggest that weight loss can decrease the severity of OSAS,7 but it may not reverse the pathophysiology completely owing to the multifactorial nature of the disease. Advice should also be given about changing sleeping position, eg advising a patient to sleep on their side rather than on their back, and on avoidance of alcohol or stimulants prior to bed. In moderate to severe OSAS, or where the impact on daily life is significant, the mainstay of therapy is the use of positive pressure ventilation at home, via a continuous positive airways pressure (CPAP) machine. The patient is provided with a small device and a mask, which they wear over their nose and mouth overnight. The machine produces a continuous positive filtered airflow, which splints the upper airways open, allowing the patient to breathe spontaneously but preventing upper airway narrowing or collapse. The pressures can be altered to meet the needs of individual patients. A 2006 Cochrane meta-analysis by Giles et al,16 evaluating 36 studies, concluded that CPAP was a highly effective intervention, decreasing AHI by up to 8 Prescriber August 2016 ❚ 25

■ THERAPY FOCUS l Obstructive sleep apnoea

•P  atients with excessive daytime sleepiness, regardless of cause or a formal diagnosis of OSAS, should not drive if sleepiness occurs to a degree that could impact on the ability to drive safely, eg ability to complete an emergency stop • Where a diagnosis of OSAS is suspected or made, medical professionals are obligated to inform patients of their responsibilities with regard to the DVLA • If OSAS is suspected or diagnosed, patients are responsible for notifying the DVLA and completing the relevant paperwork. They may then be asked to refrain from driving until they have received treatment and symptoms are adequately controlled • Once symptoms are controlled, patients may be allowed to return to driving if deemed safe to do so following ongoing assessment and liaison with the DVLA Table 4. DVLA guidance on obstructive sleep apnoea syndrome (OSAS)

points, with improved quality of life and decreased daytime sleepiness. In practice, use of home CPAP is associated with variable patient compliance. Provision of home machines involves a specialist multidisciplinary sleep medicine team, who work closely with the patient to teach independent setup of equipment each night, provide advice and expertise on mask fit, and then monitor the patient on an ongoing basis to assess compliance with the machine, alteration of settings and improvement in symptoms. The number of hours of use overnight is recorded by the machine and can be reviewed at follow-up appointments. The recordings can be used together with blood gas sampling to adjust individual requirements, aiming to normalise biochemical evidence of chronic ventilatory failure and improve quality of life. However, as most sleep units are based at tertiary care centres, logistical arrangements for patients to attend appointments for assessment and follow-up can be complex, and poor tolerance of the machine or mask overnight can be a significant issue. Up to 20 per cent of patients may discontinue therapy because of issues around mask fit, discomfort or leak,17 emphasising the importance of follow-up and contact within the specialist unit for troubleshooting. The efficacy of CPAP can be accessed by questioning the patient directly regarding symptoms and repeating the ESS score, with the greatest improvement usually seen within the first six months of use. Other treatment options for OSA include oral appliances to help splint the upper airways open and oral surgery to 26 ❚ Prescriber August 2016

alter the local anatomy, eg uvulopalatopharyngoplasty, but these are usually reserved for those patients in whom CPAP has failed as an intervention. There is limited evidence for their effects on daytime sleepiness, but some effect on AHI score has been demonstrated in small trials.18

Complications and future prospects Alongside our increasing understanding of OSAS as a disease is a growing body of knowledge about its associated co-morbidities. More importantly, we are increasingly recognising that controlling the pathological processes underpinning OSAS may also help control such co-morbidities, and vice versa. Perhaps the most well-established link is between OSAS and vascular risk, in particular a connection with resistant hypertension (defined as blood pressure >140/90mmHg despite the use of three or more antihypertensive agents). The recurrent arousals during episodes of apnoea in OSAS and associated sympathetic surges drive adrenaline release, resulting in highly fluctuating blood pressure, which can in turn cause arterial wall shear stress and endothelial cell dysfunction, leading to the development of hypertension over time. A meta-analysis by Iftikhar et al. in 2014 19 looked at six studies that assessed hypertension pre- and post­ intervention with CPAP for the treatment of OSAS, and found an overall mean net change of -7mmHg in systolic blood pressure over 24-hour monitoring in patients using CPAP; a modest improvement. Another meta-analysis conducted by Schein et al.20 looked at 16 randomised

controlled trials and found similar modest improvements in blood pressure following OSAS treatment. However, what is not yet well characterised is how well treatment of OSAS protects against vascular-related morbidity and mortality, and various prospective studies are ongoing to assess this.21 The link between coronary heart disease (for which vascular disease can be considered a surrogate marker) and OSAS is also being investigated. Similarly, a high prevalence of type 2 diabetes in patients with OSAS is also recognised.22 OSAS and the spectrum of co-morbidities comprising metabolic syndrome, diabetes and fatty liver disease share common features of high levels of fat deposition and insulin resistance in peripheral tissues, and so it is unsurprising that these diseases often co-exist. However, studies to date suggest that CPAP is of limited benefit in reducing insulin resistance.23-25

Conclusion OSAS continues to be a significant and underdiagnosed respiratory cause of morbidity. The condition is often identified in the primary care setting, and may present via a collateral history from a bed partner rather than the patient themselves. Formal diagnosis requires overnight sleep studies, usually carried out at tertiary sleep units. The mainstay of therapy for moderate or severe OSAS continues to be CPAP, initiated with the support of a multidisciplinary sleep and ventilation team. It is becoming increasingly recognised that OSAS can exist in parallel with, and contribute to, a number of other medical conditions, and control of OSAS via conservative and medical therapies may potentially assist in the management of these conditions.

References 1. Peppard PE, et al. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 2013;177(9):1006–14. 2. Steier J, et al. Predicted relative prevalence estimates for obstructive sleep apnoea and the associated healthcare provision across the UK. Thorax 2014;69(4):390–2. 3. Heinzer R, et al. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med

prescriber.co.uk

Obstructive sleep apnoea

2015;3(4):310–8. 4. Remmers JE, et al. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol: Respir Environ Exerc Physiol 1978;44(6): 931–8. 5. Fogel RB, et al. Sleep. 2: pathophysiology of obstructive sleep apnoea/hypopnoea syndrome. Thorax 2004;59(2):159–63. 6. Wellman A, et al. Ventilatory control and airway anatomy in obstructive sleep apnea. Am J Respir Critical Care Med 2004;170(11):1225– 32. 7. Peppard PE, et al. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA 2000;284(23):3015–21. 8. Young T, et al. Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. Arch Intern Med 2002;162(8):893–900. 9. Newman AB, et al. Progression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study. Arch Intern Med 2005;165(20):2408– 13. 10. Whittle AT, et al. Neck soft tissue and fat distribution: comparison between normal men and women by magnetic resonance imaging. Thorax 1999;54(4):323–8. 11. Bixler EO, et al. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Critical Care Med 2001;163(3, Pt 1):608–13.

prescriber.co.uk

12. Seicean S, et al. Sleep-disordered breathing and impaired glucose metabolism in normal-weight and overweight/obese individuals: the Sleep Heart Health Study. Diabetes Care 2008;31(5):1001–6. 13. Teodorescu M, et al. Association between asthma and risk of developing obstructive sleep apnea. JAMA 2015;313(2):156–64. 14. NICE Clinical Knowledge Summaries. Obstructive sleep apnoea syndrome. April 2015. http://cks.nice.org.uk/obstructivesleep-apnoea-syndrome#!scenario 15. Drager LF, et al. Characteristics and predictors of obstructive sleep apnea in patients with systemic hypertension. Am J Cardiol 2010;105(8):1135–9. 16. Giles TL, et al. Continuous positive airways pressure for obstructive sleep apnoea in adults. Cochrane Database Syst Rev 2006(3):CD001106. 17. Haniffa M, et al. Inter ventions to improve compliance with continuous positive airway pressure for obstructive sleep apnoea. Cochrane Database Syst Rev 2004;4:CD003531. 18. Browaldh N, et al. SKUP3 randomised controlled trial: polysomnographic results after uvulopalatopharyngoplasty in selected patients with obstructive sleep apnoea. Thorax 2013;68(9):846–53. 19. Iftikhar IH, et al. Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis. J

l THERAPY FOCUS ■

Hypertension 2014;32(12):2341–50. 20. Schein AS, et al. Continuous positive airway pressure reduces blood pressure in patients with obstructive sleep apnea; a systematic review and meta-analysis with 1000 patients. J Hypertension 2014;32(9):1762–73. 21. Wons AM, Kohler M. Established vascular effects of continuous positive airway pressure therapy in patients with obstructive sleep apnoea – an update. J Thoracic Dis 2015;7(5):912–9. 22. West SD, et al. Prevalence of obstructive sleep apnoea in men with type 2 diabetes. Thorax 2006;61(11):945–50. 23. West SD, et al. Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes. Thorax 2007;62(11):969–74. 24. Sharma SK, et al. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. New Engl J Med 2011;365(24):2277–86. 25. Weinstock TG, et al. A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. Sleep 2012;35(5):617–25B.

Declaration of interests None to declare. Prashanthi Ratnakumar is a core medical trainee in Oxford Deanery and Ari Manuel is a consultant at Cheltenham General Hospital

Prescriber August 2016 ❚ 27