GORD treatment reduces daytime sleepiness in OSA patients – further evidence for a causal link between the two conditions?

Sleep apnoea is extremely common. It affects 5% of Australian women and up to 10% of men.1 The most common cause of sleep apnoea is obstructive-sleep disordered breathing (OSDB).2 OSDB occurs when there is a physical block of the airway causing apnoeas during sleep. Each time breathing is paused, sleep is disrupted. The sufferer is rarely fully awoken by these apnoeas, but their brain is awoken enough to tighten the airway muscles so breathing returns to normal. This can happen continuously throughout the night without the sufferer realising.

As well as headache, snoring, heartburn and breathlessness, sufferers of OSBD also very commonly experience extreme daytime sleepiness due to the constant interruption of sleep.³ Extreme daytime sleepiness has a significant impact on driving safety;¹ termed the “silent killer” as approximately 30% of all road deaths are caused by fatigued drivers.⁴ Additionally, quality of life is affected due to sleep-deprivation causing abnormalities in attention, memory, mood and performance.⁵

There are many factors that can account towards OSDB. Predominantly individuals that are overweight or obese are at risk due to the narrowing of the upper respiratory tract associated with excessive weight.³ Obesity also increases the prevalence of Gastro-oesophageal reflux disease (GORD).

Dr Michael Pritchard Respiratory and Sleep Physician and Director of the Perth Sleep Clinic said “Gastro-oesophageal reflux is very common in association with obstructive sleep apnoea, perhaps as much as 2/3 of obstructive sleep apnoea patients have measurable nocturnal reflux, often high reflux.”

Although these two conditions are very commonly expressed comorbidly a direct causal link between the two is yet to be identified.^6,7 Many possible hypotheses regarding their temporal relationship have been put forth;

GORD is a predominant cause of OSDB; mucousal reflux being an airway obstruction,^2,7
Bronchospasms induced by vagal reflux cause airway obstruction,⁶
Inflammation caused by prolonged reflux symptoms weakens the airway smooth muscle, worsening airway obstruction and also worsening airway narrowing associated with obesity.^7,8

Studies have attempted to determine which causal relationship, if any, exists between OSDB and GORD and in the process have identified that treating GORD can have positive outcomes of symptoms of OSDB.⁷

Steward (2004) has shown that treatment for GORD with proton-pump inhibitors (PPIs) can reduce daytime sleepiness.⁹ Specifically, researchers found that researchers found that pantoprazole decreased daytime somnolence induced via obstructive sleep apnoeas. The number of awakenings due to acid reflux, were are estimated to account for half of the apnoeas experienced in OSDB.⁹ However, further research was required to validate these results and to further investigate the beneficial effects of pantoprazole on OSDB.⁹Steward was limited as there was no control condition to compare the effects. The authors therefore concluded that further studies need to be conducted in order to determine whether the reduction in daytime sleepiness was in fact due to a decrease in awakenings due to acid reflux and not a placebo effect.⁹

The present study (Suurna et al, 2008) was conducted to replicate and extend the findings of Steward.⁹It aimed to determine the beneficial effects, if any, of once-daily pantoprazole (Somac) treatment on OSDB and acid reflux in a sample of participants suffering from both GORD and OSDB.⁸ Symptoms of daytime sleepiness, acid reflux and sleep related quality of life were assessed over six weeks. Psychomotor vigilance (reaction times) was also assessed in order to determine whether pantoprazole may also have a beneficial effect on driving.⁸

In this study, pantoprazole (Somac) was again found to improve daytime sleepiness as well as acid reflux and could potentially present a complimentary pharmacological treatment for OSDB.⁸

Currently OSDB is treated using continuous positive airway pressure (CPAP). This treatment is effective when used every night, however many patients do not adhere strictly enough for it to have a beneficial effect.² Hence a drug intervention with PPIs to manage OSBD would be a hassle-free, favourable alternative treatment option for some sufferers.^8,9

The outcome measures for the study were as follows:⁸

Daytime Somnolence as assessed by the Epworth Sleepiness Score (ESS);
Acid Reflux based on reflux scores obtained from the validated GORD questionnaire;
Sleep-related quality of life as assessed by the validated questionnaire (FOSQ); and
Psychomotor vigilance as assessed by a reaction time task.

The investigation was designed as a randomised, double-blind, placebo-controlled, repeated measures analysis of 40mg pantoprazole versus placebo. Each participant was randomised into drug first or placebo first treatments. The measures were assessed at baseline then the treatments lasted for 2 weeks, at the end of which was a 2 week washout period. At the conclusion of the washout period the outcomes were assessed and this served as a secondary baseline measure. Then the participants swapped conditions. At the conclusion of the two week treatment sections the outcomes were assessed and compared to the previous baseline measure.⁸

The mean results for each condition obtained from both of the outcomes were subjected to a two-way multivariate analysis to test for significant differences between the two. P values of > 0.05 were deemed significant.⁸

57 mild to moderate OSDB sufferers with comorbid GORD signs and symptoms participated and completed the study. Exclusions included any patients with non-obstructive sleep apnoeas or any patients who were currently using any other treatment device to combat their sleep disturbances.⁸

The final sample of participants had a mean age of 51 and all were moderately obese (Mean BMI = 31).⁸

The results were as follows:⁸

Pantoprazole (Somac) significantly improved daytime sleepiness;
Pantoprazole significantly improved acid reflux;
Sleep related quality of life was improved in both the pantoprazole and placebo condition;
Psychomotor vigilance was not differentially affected by pantoprazole; and
Reflux related sleep arousal was not significantly different between the two groups but a non-significant (P = 0.096) trend was found.

This study successfully improved some OSDB symptoms by treating an underlying cause for the apnoeas, GORD.

Daytime sleepiness was significantly improved in the pantoprazole (Somac) condition compared to the placebo condition. This indicated once again that a substantial amount of obstructive apnoeas experienced by this sample of patients are caused by acid reflux; as the daytime sleepiness was reduced substantially when the pH of the acid reflux was increased. The authors concluded this is most likely due to a decrease in the amount of reflux-related arousals during sleep. However there was only a trend (0.096) toward decreased reflux-related arousals in the PPI condition and therefore needs to be further investigated.⁸

Dr Pritchard said “There is a role for pharmacological therapy of sleep maintenance insomnia due to reflux in patients with OSA, however that is not to say that PPI therapy treats upper airway obstruction.”

The frequency of obstructive sleep apnoeas were not improved with pantoprazole indicating that it is not acid reflux alone that is causing the OSDB.⁸ This is consistent with Steward (2004).⁹ Further to support this is the finding that insomnia is found in patients with GORD symptoms but not OSDB, suggesting that acid reflux can disrupt sleep without being associated with obstruction of the airways.⁶ However, it most likely worsens OSDB when it co-exists.

“Since sleep disturbance due to nocturnal reflux is probably underestimated, a trial of pharmacological therapy and dietary modification is warranted prior to initiating CPAP in selected patients. If OSAH has been proven or strongly suspected, and coexists with GORD, one should not assume that improvement in daytime sleepiness on PPI equates to successful treatment of OSAH” said Dr Pritchard.

The decrease in daytime sleepiness did not correspond to an increase in reaction time, suggesting that pantoprazole alone will not completely combat the risk of overtired driving. However these same psychomotor vigilance tasks should be tested in healthy controls to assess whether OSDB patients differ. Accidents due to tiredness on the roads are not necessarily due to an impaired reaction time. An improvement in daytime sleepiness with or without an improvement in reaction time is highly beneficial for OSDB drivers.⁸

Both OSDB and acid reflux are prevalent in overweight and obese people who seem to experience OSDB due to narrowing of the pharyngeal muscles and their subsequent collapse during sleep;³ highlighting that weight control must still be considered the long term frontline treatment plan.

References

Sleep Apnoea Fact Sheet. Sleep Disorders Australia, Kent Town, South Australia. 2008.
Anttalainen U, Saaresranta T, Kalleinen N, Aittokallio J, Vahlberg T, Polo O. CPAP adherence and partial upper airway obstruction during sleep. Sleep Breath. 2007; 11:171–176.
Narcolepsy and Overwhelming Daytime Sleep [online]. (cited 2008 Oct 29). Available from: URL: http://www.nodss.org.au/
Fatigue [online]. 2008 (cited 2008 Oct 31). Available from: URL: http://www.officeofroadsafety.wa.gov.au/
Thomas RJ. Arousals in Sleep-disordered Breathing: Patterns and Implications. Sleep. 2003; 26(8): 1042-1047.
Shaheen NJ, Madanick RD, Alattar M et al. Gastroesophageal reflux disease as an etiology of sleep disturbance in subjects with insomnia and minimal reflux symptoms: a pilot study of prevalence and response to therapy. Digestive Diseases and Sciences. 2008; 53(6): 1493-1499
Zanation AM, Senior BA. The relationship between extraesophageal reflux (EER) and obstructive sleep apnea (OSA). Sleep Med Rev. 2005; 9(6): 453-458
Suurna M, Welge J, Surdulescu, Kushner J, Steward DL. Randomized placebo-controlled trial of pantoprazole for daytime sleepiness in GERD and obstructive sleep disordered breathing. Oto Head Neck Surg. 2008; 139: 286-290.
Steward DL. Pantoprazole for sleepiness associated with acid reflux and obstructive sleep disordered breathing. Laryngoscope. 2004; 114(9): 1525-1528.