Editorial

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Obstructive sleep apnea: should weight loss be prescribed?

Expert Rev. Respir. Med. 7(1), 13 (2013)

Kirk Kee
Department of Medicine, Monash University, Melbourne, Australia and Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia

In those who have symptomatic or severe obstructive sleep

apnea, weight loss should be used as an adjunct to more effective treatment, which should not be delayed.

Matthew T Naughton
Author for correspondence: Department of Medicine, Monash University, Melbourne, Australia and Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia Tel.: +61 3 9076 3770 Fax: +61 3 9076 3601 m.naughton@alfred.org.au

Obstructive sleep apnea (OSA) is a highly prevalent disease which has signicant public health consequences including increased cardiovascular risk, motor vehicle accidents and impaired cognitive function. The diagnosis of OSA carries with it a threefold increase in mortality risk [1] . The strongest risk factor for OSA is increasing weight with a fourfold increase in prevalence for every one standard deviation increase in BMI [2] . Longitudinal increases in weight result in increasing severity of OSA while reductions in weight have an opposite, although smaller effect [3,4] . In those without OSA, a 10% increase in weight is associated with a sixfold increase in the risk of developing moderate-to-severe OSA [4] . For this reason, weight loss is recommended in the management of OSA [57] .
Weight loss

has also been trialed however, its success has been limited and there have been concerns with the long-term safety in the most well-studied medication [8] . A meta-analysis of weight loss trials demonstrated that interventions that included some form of dietary restriction and/or medication were effective at reducing weight by a mean of 58.5kg (59% of initial body weight). Moreover, in those studies with 4years follow-up, weight loss was maintained at 36kg (36%). By contrast, exercise-only or advice-only interventions showed no benet at any point in time [9] .
Randomized controlled trials of weight loss in OSA

Despite this widespread recommendation, the evidence base for weight loss as a treatment for OSA is poor. There is a scarcity of randomized control trials and the issue is further clouded by the multitude of techniques which can be used to achieve weight loss. Weight loss management can range from a simple recommendation to lose weight by the treating physician to more extreme measures such as bariatric surgery. In between, there are various forms of behavioral and lifestyle modication including very low calorie diets (VLCD). Pharmacotherapy

Whether the amount of weight loss provided by dietary restriction translates into meaningful reductions in OSA, severity appears to vary depending on disease severity. We identied four randomized trials that provide data on this topic. The primary end point for all of these trials was change in the apneahypopnea index(AHI). In Finland, Tuomilehto etal. looked at 72 overweight subjects (BMI: 2840kg/m2) with mild OSA (AHI 515 events per hour [eph]) who were randomized to either intensive lifestyle modification including a VLCD or general advice (a single dietary and exercise session). The group mean demo graphics were 65% male, aged 51years, weight 96.8kg, BMI 32.4kg/m2 and AHI 6.7eph. Compared with the

KEYWORDS: bariatric surgery diet obstructive sleep apnea sleep disordered breathing weight loss

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10.1586/ERS.12.78

2013 Expert Reviews Ltd

ISSN 1747-6348

Editorial

Kee & Naughton

control group the lifestyle modication group had a greater change in weight (-10.76.5 vs-2.45.6kg; p<0.001) and AHI (-4.05.6 vs 0.38eph; p=0.011) and more patients were cured (AHI: <5eph; 63vs13%; p=0.033) at 1year [10] . Two further studies, published in the same year, looked at patients with more severe OSA. The rst studied 63 obese (BMI: 3040) patients with OSA (AHI: >15) in Sweden: all were male with a mean age of 49years, weight: 112.5kg, BMI: 34.6kg/m 2 and AHI: 37eph. They were randomized to either a liquid VLCD of 2.3MJ per day or their usual diet for 9weeks. Compared with controls, those on the liquid diet had a greater change in weight (-18.74.1 vs 1.11.9kg; p<0.001) and AHI (-2517 vs -21eph; p<0.001), with more cured (i.e.,AHI:<5; 18 vs 0%) [11] . The authors completed a 12-month follow-up study where patients from the same study were pooled into one cohort. Patients from the control arm were then provided with the same 9-week VLCD. The entire cohort was followed up for 1year. In the longer-term study, weight loss 12months after the 9-week intervention remained signicant (-12.19kg; p<0.001) and AHI was also signicantly lower (-1716eph; p<0.001) [12] .

Of note, patients in both groups remained obese at the end of the study (BMI: 37 vs 42kg/m2) and most still had signicant OSA and their CPAP pressures were unchanged. Only one patient, who was in the conventional program, was cured.
Conclusion

...we believe that weight loss can be an important

component of obstructive sleep apnea management. A larger study collected 264 patients in USA with Type 2 diabetes, obesity (BMI: >25kg/m2) and OSA (AHI: >5eph) as part of a larger study looking at the effect of weight loss on diabetic control [13] . The group demographics were 59% female, aged 61years, weight: 102.4kg, BMI: 36.7kg/m2 and AHI: 23.2eph. Patients were randomized to either a behavioral weight loss program or three sessions of general diabetes education. The behavioral weight loss program included the provision of portion-controlled diets including liquid meal replacements, frozen food and snack bars for the rst 4months of the study. The behavioral weight loss group lost more weight (10.80.7 vs 0.60.7kg; p<0.001) and had a greater fall in AHI (-5.41.5 vs 4.21.4eph; p<0.001) after 1year [13] . Over twice as many patients in the weight loss group had a fall in their OSA severity category (estimated 40 vs 18%). OSA cure was seen in 36% of the active and only 10% in the conservative arm. BMI was similar in the three studies previously described. The fourth trial from Australia involved 60 severely obese patients (BMI: 3555kg/m2) with OSA (AHI: >20eph) who were recommended continuous positive airway pressure (CPAP) treatment. They were randomized to either bariatric surgery ( laparoscopic adjustable gastric banding) with lifestyle modication or lifestyle modication alone (conventional program) [14] . The group demographics were 58% male, aged 49years with baseline BMI: 45.1kg/m2 and AHI: 61.1eph. The lifestyle modication included dietary, exercise and behavioral advice as well as the offer of VLCD meal replacement. After 2years, the bariatric surgery group had signicantly more weight loss (-27.8 vs -5.1kg; p<0.01) but there was no difference in change in AHI (-25.5 vs -14.0eph; p=0.18) compared with the conventional program.
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The rising incidence of obesity and its related co-morbidities threatens to replace smoking in much the same way smoking replaced infectious disease as the major public health issue confronting the medical fraternity. Like smoking, signicant public health benet will come not from treating obesity-related disease but from preventing or curing obesity itself. While the traditional methods of diet and exercise can be effective there is a host of other contributors to the obesity crisis which need to be addressed [15] . Bariatric surgery will play a role in the very obese but widespread availability is unlikely. It is also important to realize that the term bariatric surgery encompasses a variety of techniques that have varying success rates and associated morbidity [16] . About the use of weight loss as a treatment for OSA, it is clear that reductions in weight result in improvements in OSA severity. It is also clear that weight loss as a treatment does not include just physician advice or one-off counseling. All ve of the effective arms in the studies above included a VLCD and signicant support in the form of ongoing counseling and lifestyle advice. Whether this form of intensive weight loss program can be made readily available in the future remains to be seen, but we suspect that the great majority of OSA patients who are advised to lose weight at present do not get what the evidence suggests are required. In those in whom signicant weight loss can be achieved and maintained, current evidence suggests that disease severity can be improved and in some cases cure achieved. Patients with mild disease and relatively low BMI are most likely to be cured. However, given increased cardiovascular risk appears concentrated in those with severe disease (AHI: >30eph) [17] , reduction in severity may be of benet especially in those who are intolerant of more effective therapy such as CPAP. It is also likely that obese patients with severe OSA have other comorbidities which would benet from weight reduction. For example, bariatric surgery resulted in a signicant improvement in HbA1c in those OSA patients with Type 2 diabetes [14] . In summary, we believe that weight loss can be an important component of OSA management. It does however require signicant resources and patient buyin to be achieved. In those who have symptomatic or severe OSA, weight loss should be used as an adjunct to more effective treatment, which should not be delayed.
Financial & competing interests disclosure

The authors have no relevant afliations or nancial involvement with any organization or entity with a nancial interest in or nancial conict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Expert Rev. Respir. Med. 7(1), (2013)

Obstructive sleep apnea: should weight loss be prescribed?

Editorial

References
Papers of special note have been highlighted as: of interest of considerable interest
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of obstructive sleep apnea in adults. J. Clin. Sleep Med. 5(3), 263276 (2009). James WP, Caterson ID, Coutinho W etal.; SCOUT Investigators. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N. Engl. J. Med. 363(10), 905917 (2010). Franz MJ, VanWormer JJ, Crain AL etal. Weight-loss outcomes: a systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up. J. Am. Diet. Assoc. 107(10), 17551767 (2007). Meta-analysis emphasizes the importance of very low calorie diets in weight loss and the ineffectiveness of counseling or exercise on its own. Tuomilehto HP, Sepp JM, Partinen MM etal.; Kuopio Sleep Apnea Group. Lifestyle intervention with weight reduction: rst-line treatment in mild obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 179(4), 320327 (2009). Johansson K, Neovius M, Lagerros YT etal. Effect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trial. BMJ 339, b4609 (2009). Johansson K, Hemmingsson E, Harlid R etal. Longer term effects of very low energy diet on obstructive sleep apnoea in cohort derived from randomised controlled trial: prospective observational follow-up study. BMJ 342, d3017 (2011). Foster GD, Borradaile KE, Sanders MH etal.; Sleep AHEAD Research Group of Look AHEAD Research Group. A

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randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with Type 2 diabetes: the Sleep AHEAD study. Arch. Intern. Med. 169(17), 16191626 (2009). Largest randomized controlled trial of weight loss for obstructive sleep apnoea demonstrating the effectiveness of verylow calorie diets and lifestyle modification on weight.
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Dixon JB, Schachter LM, OBrien PE etal. Surgical vs conventional therapy for weight loss treatment of obstructive sleep apnea: arandomized controlled trial. JAMA 308(11), 11421149 (2012).

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Demonstrated that weight loss, irrespective of method achieved significant improvement in obstructive sleep apnoea severity.
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McAllister EJ, Dhurandhar NV, Keith SW etal. Ten putative contributors to the obesity epidemic. Crit. Rev. Food Sci. Nutr. 49(10), 868913 (2009). Dixon JB, Straznicky NE, Lambert EA, Schlaich MP, Lambert GW. Surgical approaches to the treatment of obesity. Nat. Rev. Gastroenterol. Hepatol. 8(8), 429437 (2011). An excellent review of the current surgical approaches to bariatric surgery. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoeahypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365(9464), 10461053 (2005).

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