While it was thought that the internationally approved gold standard treatment was sufficient to control obstructive sleep apnoea and its dangerous consequences, a major French study shortly to be published in the European Respiratory Journal (ERJ) will certainly set the cat among the pigeons.

Approximately 10% of the subjects given the approved treatment continue to suffer from daytime sleepiness, according to the study based on results from over 500 patients in some forty sleep study centres. This would mean over 14,000 patients affected in France alone and some half million people globally. The authors emphasise that there is an urgent need to identify these patients and provide other associated treatments.

There is still little awareness of obstructive sleep apnoea syndrome (OSAS) among the general public and even some doctors, although it is a dangerous condition in a number of respects. Increasingly widespread, this chronic disease (currently believed to affect at least 5% of middle-aged men and women, though the number of apnoeic subjects could be much higher) is often associated with snoring. It is caused, in fact, by a temporary blockage of the pharynx during sleep; this lasts for ten seconds or more and may happen up to thirty times each hour throughout the night. The turbulence generated by the closure of the airways in each episode gives rise to the characteristic sound of snoring.

Such fragmented sleep and the resulting drop in blood oxygen levels have a number of adverse consequences for the subject’s health and quality of life. Not only can frequent apnoeic episodes multiply the sufferer’s risk of cardiovascular disease by five, they also have a direct impact on day-to-day life.

The apnoeic patient, deprived of healing sleep, is perpetually tired, has greater difficulty in concentrating during the day, and, above all, suffers from daytime sleepiness that can have very serious consequences. In particular, it can lead to road accidents: some 25% of apnoeic drivers report having fallen asleep at the wheel at least once. This problem could affect five million drivers in Europe!

Measuring sleepiness

The stakes were thus sufficiently high for specialists to develop a simple treatment for the damage caused by apnoea. CPAP, or continuous positive airway pressure, invented over 25 years ago, has become an internationally recognised standard. At night, the patient wears a mask similar to those used by fighter pilots, which covers the nose and mouth and provides the continuous airway pressure that keeps the pharynx open during sleep and prevents apnoea and snoring.

While most patients treated with this method report a considerable improvement in quality of life, some seem to obtain only partial benefit. This is the backdrop to the discovery by the team working under Jean-Louis Pépin at the Sleep Laboratory of the University of Grenoble, whose results are published in the forthcoming issue of the ERJ.

Determined to shed some light on this paradox, the team monitored 502 patients in 37 French sleep laboratories. Slightly over three-quarters (78%) of the subjects, aged 59 on average, were male and all had been treated with CPAP for at least three hours per night for at least one year.

After assessing the volunteers’ general condition, the quality of their sleep and their compliance with the treatment, the Grenoble team also measured their quality of life and daytime sleepiness using the Nottingham and Epworth scales respectively.

The Epworth scale, a very simple means of assessing daytime sleepiness, requires patients to report their likelihood of dozing in various situations, such as watching TV, sitting in the theatre or a meeting, or as a passenger in a car. Eight situations (scored from 0 to 3) provide a global assessment of the subject’s daytime sleepiness on a scale from 0 to 24. Excessive sleepiness is indicated by a score over 12.

Some mystery

The prevalence that emerged from this groundbreaking study came as a surprise even to their authors.

No less than sixty of the 500 patients monitored (12%) were found, on the day of examination, to have a high level of daytime sleepiness, with an Epworth score between 11.8 and 16.8.

In certain patients, the sleepiness was associated with three other conditions: “restless leg syndrome” (characterised by an uncontrollable urge to move the legs, which can disturb sleep at night); a depressive state; and narcolepsy. The latter condition is rare and characterised mainly by sudden attacks of sleep in the daytime, which sometimes cause the subject to fall over as sleep relaxes the muscles.

Since these three conditions were liable to reduce subjects’ daytime alertness and distort part of the results, Pépin and his colleagues decided to play it safe and exclude them from the analysis. Despite this adjustment, there remained thirty subjects with unexplained residual daytime sleepiness, which represented six per cent of the apnoeic patients treated with the renowned CPAP!

It should be noted, however, that the method had shown good results in treating the apnoea itself, but the daytime sleepiness continued, paradoxically, to handicap these patients.

The reason was somewhat mysterious. Especially since basic characteristics, including sleep duration and body mass index, were similar for patients with residual daytime sleepiness and those without.

“The only difference we noted between the two groups”, Pépin explains in the ERJ, “was age: the subjects with residual sleepiness even after CPAP were on average six years younger than those whose symptoms were completely eliminated.”

The study’s authors also note that, when the initial diagnosis of sleep apnoea was made, the subjects in question already had a greater sleepiness problem. “Above all, they complained more about tiredness and not feeling refreshed after sleep”.

The only solution for these patients at present would be to ask their doctor for psychostimulants, such as modafinil or one of the molecules currently under development, to help them avoid constant drowsiness.

Half a million people affected

This study’s conclusions could have wide-ranging repercussions. Since obstructive sleep apnoea is a common condition among the general population, the French team’s results would suggest that a very large number of people have residual daytime sleepiness. “In France alone, we have 230,000 patients using continuous positive airway pressure. We calculate that at least 13,800 of those have residual daytime sleepiness”, notes Pépin. These figures suggest a worldwide total of at least 500,000 people undergoing treatment for apnoea but still suffering from a dangerous level of daytime sleepiness!

“The youngest and sleepiest patients at the time of diagnosis are the most vulnerable and require rigorous follow-up and assessment”, Pépin emphasises. In his view, daytime sleepiness is not sufficiently researched by doctors, even – or especially – if the apnoeic patient is given the gold standard treatment. To make it worse, this type of problem is usually not reported spontaneously by patients, who are often not aware of it.

“There is no need to tolerate persistent daytime sleepiness in patients under treatment. Patients and doctors should seek better results”, insists Pépin. What remains unclear is the potential long-term evolution of this residual daytime sleepiness and whether – in addition to its impact on quality of life – it represents a risk factor for cardiovascular disease or other pathologies.

As to an explanation for this failure of the gold standard treatment, the ERJ article’s authors are hypothesising, based on brain imaging, that, over time and in certain subjects only, sleep apnoea might cause irreversible lesions in the oxygen-deprived brain, thus leading to persistent drowsiness and a reduction in cognitive function.

Source: European Respiratory Journal (European Respiratory Society)