• obstructive sleep apnoea/hypopnoea syndrome

In 1997 Dr Wright and colleagues published a systematic review on the health effects of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) and the effectiveness of treatment with continuous positive airway pressure (CPAP).¹ They concluded that there was limited evidence of increased mortality or morbidity in patients with OSAHS, and that the evidence linking the condition to cardiac arrhythmias, ischaemic heart disease, left and right ventricular dysfunction, systemic and pulmonary hypertension, stroke, and automobile crashes was conflicting and inconclusive. They also concluded that, although CPAP had been shown to improve daytime sleepiness, there were insufficient data to determine its effect on quality of life, morbidity, or mortality. This review generated much controversy but was a wake up call² to investigators in this field that all were not convinced that OSAHS was an important condition that always warranted treatment. At that time our understanding of the natural history of OSAHS and the impact of treatment was at a similar stage to where we were with systemic hypertension and hypercholesterolaemia several decades ago. Considerable progress has been made in the past six years since the publication of this review, and many of the issues which it raised have started to be addressed. Long term population based prospective cohort studies have been initiated to examine the association of OSAHS with morbidity and mortality. Additional studies have been performed to determine the link between OSAHS and automobile crashes. A variety of large, well designed, randomised controlled trials have been completed or are in progress to determine the indications, benefits, and risks of treatment of OSAHS.

An important first step in this process was performed by an international task force in 1997 which developed definitions of sleep disordered breathing (SDB) and recommendations for measurement techniques.³ OSAHS was characterised as recurrent episodes of partial or complete upper airway obstruction during sleep. The diagnostic criteria for OSAHS were >5 apnoeas or hypopnoeas/h during sleep (the apnoea/hypopnoea index, AHI) and the presence of either excessive daytime sleepiness or two other symptoms (nocturnal choking, recurrent awakening, unrefreshing sleep, daytime fatigue, or impaired concentration). Nasal pressure or respiratory inductance plethysmography were recommended as the preferred techniques for measuring apnoea and hypopnoea. Apnoeas or hypopnoeas were defined as events of 10 seconds or longer with either a >50% decrease in amplitude of a valid measure of breathing during sleep or a <50% decrease with either a 3% desaturation or arousal. The severity of OSAHS was determined by two components—severity of daytime sleepiness and overnight monitoring (mild 5–15 events/h, moderate 15–30 events/h, severe >30 events/h)—with the final rating for the severity of the syndrome based on the most severe component.

The Wisconsin Sleep Cohort Study is a prospective community population based study initiated in 1988 which has estimated that 4% of middle aged men and 2% of women have OSAHS.⁴ Analysis of 709 participants studied for 4 years and 184 participants studied for 8 years revealed a dose-response association between SDB at baseline and the development of systemic hypertension that was independent of known confounding factors.⁵ A cross sectional study of 1741 subjects in Pennsylvania also found an independent association between SDB and systemic hypertension in young and middle aged individuals.⁶ The Sleep Heart Health Study (SHHS) is a prospective cohort study of 6424 individuals recruited between 1995 and 1998 designed to determine whether SDB is a risk factor for cardiovascular and cerebrovascular diseases. The initial cross sectional analysis⁷ was compatible with modest to moderate effects of OSAHS on a variety of manifestations of cardiovascular disease. If similar results are found in the prospective analysis, this will provide conclusive evidence linking OSAHS to the premature development of cardiovascular disease. A number of cross sectional studies based either on patient self-reports or examination of motor vehicle records have reported increased automobile crashes in patients with OSAHS.^8–10 Examination of all traffic violations and accidents in 913 participants in the Wisconsin Sleep Cohort Study revealed that men with an AHI of >5/h were significantly more likely to have at least one automobile crash in 5 years than participants without OSAHS. Men and women combined with an AHI of >15/h were significantly more likely to have multiple automobile crashes in 5 years. However, many of these studies have been subject to selection or information bias and to date there have been no prospective studies to prove that OSAHS results in increased automobile crashes.

Until the mid to late 1990s the majority of studies of the effectiveness of treatment in OSAHS were small, short term, uncontrolled, and retrospective. More recently the quality of clinical research into the treatment of OSAHS has become more rigorous. A recent meta-analysis of randomised controlled trials of CPAP in patients with OSAHS included 12 trials of 738 patients and concluded that nasal CPAP significantly improves subjective and objective sleepiness across a broad range of OSAHS severity.¹¹ Several short term, randomised, double blind, placebo controlled trials have also shown that nasal CPAP reduces systemic blood pressure.^12,13 A recent meta-analysis of randomised controlled trials of oral appliances in patients with OSAHS identified 12 trials involving 509 participants with OSAHS of varying severity.¹⁴ This review concluded that there was some evidence that oral appliances improve subjective sleepiness and AHI compared with an inactive control and that nasal CPAP appears to be more effective in improving OSAHS than oral appliances. Cheyne-Stokes breathing syndrome is another type of SDB characterised by cyclic fluctuations in breathing with periods of central apnoea or hypopnoea alternating with periods of hyperpnoea.³ Cheyne-Stokes breathing syndrome is common in patients with congestive heart failure and there is increasing evidence that nasal CPAP reduces the combined rate of mortality and cardiac transplantation in these patients.¹⁵

Several large randomised controlled multicentre trials are currently either in progress or about to start recruitment, which will provide important data concerning the effectiveness of nasal CPAP in the treatment of SDB. The Apnea Positive Pressure Long-term Efficacy Study (APPLES) is a randomised, double blind, sham controlled, multicentre trial of 1100 patients with OSAHS performed over 6 months to evaluate the long term effectiveness of nasal CPAP on neurocognitive function and quality of life. The impact of CPAP on functional outcomes in milder OSA (CAT-NAP) is a randomised, double blind, placebo controlled, multicentre trial of 270 patients with mild to moderate OSAHS over 8 weeks to determine whether CPAP treatment enhances functional status and reduces daytime sleepiness and systemic blood pressure. The Canadian CPAP trial for congestive heart failure patients with central sleep apnoea (CANPAP) is a randomised, controlled, multicentre, long term trial to determine the impact of nasal CPAP on transplant free survival in 400 patients with congestive heart failure and Cheyne-Stokes breathing.¹⁶ The effectiveness of treatment for other common conditions such as hypertension or hypercholesterolaemia has required trials of thousands of patients studied over many years. Additional trials will be required to determine which groups of patients with SDB are most likely to benefit from all the currently proposed treatments, how these patients can be identified, how much benefit can be achieved, and with what cost, side effects and complications.

In this issue of Thorax we publish the first of 10 articles by a group of international experts on OSAHS which will review these issues in more depth. The first article outlines the definitions, epidemiology, and natural history of OSAHS. Subsequent articles will review the pathophysiology, clinical presentation, and diagnosis of the condition. The relationship between OSAHS and sleepiness, cognitive function, quality of life, automobile crashes, and systemic hypertension will be examined in three articles. The role of nasal CPAP, oral appliances, and upper airway surgery in the treatment of OSAHS will also be addressed. The final article in the series will discuss paediatric OSAHS.