American Journal of Respiratory and Critical Care Medicine

To the Editor:

Physical activity attenuates obstructive sleep apnea (OSA) severity, as assessed by the frequency of apneas and hypopneas per hour of sleep (i.e., the apnea/hypopnea index [AHI]), even in absence of weight loss, but the underlying mechanisms remain unknown (13). Overnight fluid shift from the legs into the neck has been indicated as a contributor to OSA (4). We have previously shown that prevention of fluid accumulation in the legs, obtained by wearing compression stockings during the day, reduces the AHI by attenuating overnight fluid shift (5, 6). Moreover, intensified diuretic therapy reduced the AHI in proportion to the decrease in overnight fluid shift (7). Fluid accumulation in the legs is promoted by sedentary living (8, 9) and is counteracted by physical activity, which activates the musculovenous pumps (810). We hypothesized that 1 week of two periods a day of 45 minutes of moderate-speed walking will reduce the AHI in non–severely obese sedentary subjects with moderate to severe OSA by decreasing overnight fluid shift around the pharynx. Some of the results of this study have been previously reported in the form of an abstract (11).

We consecutively selected subjects having a new diagnosis of moderate to severe OSA, defined as an AHI greater than 15, and a sedentary lifestyle, defined as not practicing physical activity regularly. Subjects were excluded if they were severely obese (body mass index [BMI], >35 kg/m2) and if they had a current history of smoking or alcohol abuse, history of nasal or pharyngeal disease or other chronic disease, use of prescribed medications, and previously treated OSA. Seven men and one woman, middle-aged (age, 56 ± 11 years) and overweight (BMI, 28.9 ± 3.9 kg/m2), were randomly assigned to either a 1-week walking period (consisting of walking at a rate at which they were able to keep up a full conversation, which roughly corresponds to a speed of 5 km per hour, 45 minutes twice a day, late in the morning and late in the afternoon, for 7 days, while maintaining usual activities for the rest of the time) or to a 1-week control period, after which they crossed over to the other group. Physical activity was measured over the walk and control periods using ActiGraph GT3X+ (ActiGraph LLC, Fort Walton Beach, FL) in terms of the mean number of steps taken a day during the week with and without physical activity, respectively, which reflects the daily amount of walking and is a marker of musculovenous pump activation. Polysomnography and measurement of overnight changes in legs fluid volume by bioelectrical impedance (4), in neck circumference (4), and in air volume of the pharynx from the hard palate level to the upper border of the hyoid bone by magnetic resonance imaging were performed at the end of the walk and control periods.

At the end of the control period, a substantial reduction in leg fluid volume (Figure 1) and a pronounced increase of neck circumference (Table 1) did occur overnight, indicating a significant shift of fluid from the legs into the neck. This overnight rostral fluid shift was accompanied by a 12% reduction in pharyngeal air volume, attributable to the accumulation of fluid in the pharyngeal walls (Figure 1 and Figure E2 in the online supplement). The average AHI values at the end of the control period indicate severe OSA (Figure 1). Compared with the end of the control period, at the end of the walk period, there was an 80% increase in the mean number of steps taken a day (Table 1), accompanied by a significant reduction in the overnight fluid shift by 40% (Figure 1) and in nocturnal neck enlargement by 64% (Table 1), and concomitant suppression of the nocturnal change in the pharyngeal air volume (Figure 1), in association with 30% reduction in the AHI (Figure 1), without weight and neck circumference change (Table 1). We found significant linear correlations (r = 0.796; P = 0.018) between the reduction in overnight rostral fluid shift and reduction in AHI obtained after the walk period compared with the control period, such that the greater the reduction in the amount of fluid displaced from the legs overnight, the greater the reduction in the AHI (Figure E3). There were no differences in body position during sleep, sleep quality, and architecture, except for a small increase in proportion of time spent in stage N3 (Table 1), which was not correlated (r = 0.290; P = 0.486) with the decrease in AHI, demonstrating that this is not attributable to changes in this variable.

Table 1. Number of Steps per Day, Body Weight, and Neck Circumference before Sleep and Their Overnight Changes, Overnight Water Balance, and Polysomnographic Measures for Control and Walk Periods

 Control PeriodWalk PeriodP
Steps, n/d5,915 ± 2,36210,658 ± 3,7970.010
Body weight before sleep, kg89.8 ± 13.689.1 ± 13.70.917
Neck circumference before sleep, cm*42.7 ± 2.842.8 ± 3.10.921
Change in body weight overnight, kg−0.8 ± 0.3−0.8 ± 0.50.709
Change in neck circumference overnight, cm1.1 ± 0.70.4 ± 0.50.011
Overnight water balance, ml−435 ± 209−294 ± 2010.190
 Water intake, ml115 ± 14998 ± 1160.797
 Urine volume, ml550 ± 283391 ± 2100.223
Total sleep time, min368 ± 60386 ± 570.259
Sleep time in supine position, % of total sleep time51 ± 4154 ± 410.114
Sleep efficiency, %71 ± 1276 ± 130.103
Stage N1–N2, % of total sleep time80 ± 1374 ± 130.083
Stage N3, % of total sleep time11 ± 1014 ± 130.039
Rapid eye movement sleep, % of total sleep time10 ± 712 ± 40.367
Arousal index, events/h46 ± 1235 ± 190.144
Periodic legs movement index, events/h12 ± 2014 ± 200.129

Values are expressed as mean ± SD.

*Measured in supine position. Overnight water balance is the difference between water intake and urine volume during the night.

This randomized, controlled crossover study shows that increasing the physical activity level of sedentary subjects with OSA is associated with a reduction in AHI without change in body weight. This occurs concomitantly with a reduction in the amount of fluid shifting from the legs to the pharynx overnight. In addition, this reduction in the rostral fluid shift was significantly correlated to the reduction in the AHI and accounted for 63% of its variability among subjects. These observations thus shed light on a previously not considered mechanism by which physical activity may attenuate OSA. In particular, physical activity may attenuate the severity of OSA, even in the absence of weight loss, by activating the musculovenous pump, which counteracts fluid accumulation in the legs during daytime, as well as its redistribution overnight around the pharynx.

It has been previously shown that excess fluid accumulated in the legs while upright during the day, because of gravity, and redistributed rostrally overnight on lying down, again because of gravity, may reach the neck, predisposing to OSA (4). In previous studies, the increase in neck fluid volume consequent to overnight rostral fluid shift was not directly measured, but the overnight changes in neck circumference were used as a surrogate measurement. For the first time in the present study, we showed, using magnetic resonance imaging performed before and after sleep, that the fluid displacement from the legs into the neck occurring spontaneously overnight during sleep was accompanied by an evident reduction in pharyngeal caliber, attributable to the accumulation of fluid in the pharyngeal walls.

Other mechanisms by which physical activity may reduce OSA severity have been previously proposed and only partially tested. They include sleep quality improvement with consequent respiratory stabilization, increase in strength of pharyngeal dilator muscles, decrease in nasal resistance, and enhancement of chemoreceptor sensitivity. Experimental research in individuals with OSA has produced conflicting results about changes in objective sleep quality from physical activity (13). We found a small statistically but not clinically significant increase in the amount of stage N3 sleep after the walk period, but the improvement in AHI was not found to be significantly correlated with the increase in stage N3 sleep. Even if we did not consider the other possible factors, our results strongly suggest the attenuation of overnight rostral fluid shift as a major factor responsible for the AHI reduction in the current study, accounting for 63% of its variability.

The number of subjects was small, mainly because of the complexity and the cost of the protocol. Nevertheless, because the study was performed according to a stringent clinical trial design and because the effects of physical activity on both overnight rostral fluid shift and AHI were very consistent (Figure E3), we can conclude that one of the most important implications of our observations is that physical activity can specifically act on a mechanism of disease for OSA, which is the redistribution of fluid in the pharynx walls during the night. Future studies involving more subjects over longer periods are needed, and are now justified.

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11. Redolfi S, Venturoli N, Ravanelli M, Taranto-Montemurro L, Bettinzoli M, Corda L, Pedroni L, Similowski T, Tantucci C. Physical activity attenuates fluid shift and obstructive sleep apnea [abstract]. Eur Respir J 2013;42:A4619.

*T.S. and C.T. are co–last authors.

Author Contributions: S.R., M.B., I.A., T.S., and C.T. contributed to conception, hypothesis delineation, and design; S.R., M.B., N.V., M.R., L.P., L.T.-M., I.A., T.S., and C.T. contributed to acquisition, analysis, and interpretation; S.R., M.B., I.A., T.S., and C.T. contributed to drafting the manuscript for important intellectual content.

This letter has an online supplement, which is accessible from this issue's table of contents at www.atsjournals.org

Author disclosures are available with the text of this letter at www.atsjournals.org.

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