Upper Airway Collapsibility
The Importance of Gender and Adiposity

Christopher P. O'Donnell, Alan R. Schwartz, and Philip L. Smith

Division of Pulmonary and Critical Care, Johns Hopkins School of Medicine, Baltimore, Maryland

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It is now recognized that sleep apnea is not only a common clinical problem, but one that affects men more often than women. Although initial clinical reports noted as much as a 5-to 10-fold male dominance, it appears now from a benchmark study of young to middle-aged employees in Wisconsin that men are twice as often affected (1). But why? In this issue of the Journal, Pillar and associates provide some provocative data that normal men have a more collapsible upper airway than normal women (2). By logical extension, they speculate that the increase in collapsibility may explain why men are more predisposed to the recurrent airway obstruction that is the hallmark of the disorder.

One of the major common links that drives the expression of sleep apnea in both men and women is obesity. Now, more than ever, it is recognized that even subtle changes in body mass index (BMI) may significantly alter upper airway collapsibility as well as the severity of apnea. Small decrements in weight of moderately obese individuals can reduce the collapsibility of the airway to the point of eliminating airway occlusion even though ideal body weight is not achieved (3). It is even conceivable that the small differences in BMI in Pillar's study could account for some of the gender differences (2). Interestingly, for a given severity of apnea, women have a higher BMI suggesting that the type of obesity may be playing an important role (4). The male upper body pattern of obesity compared to the female lower body distribution may offer important clues into sleep and breathing problems in general. Thus, either subtle differences in weight or body composition might explain a more collapsible upper airway in men.

Do different patterns of obesity between men and women lead to anatomical differences in the upper airway? A significant amount of anatomic data has previously shown that the airway in patients with sleep apnea compared with normal subjects is more narrow at various locations, has a different shape, and has various patterns of fat deposition (5). Interestingly, it has also been noted that the size of the upper airway is similar in men and women (6), as alluded to by Pillar and coworkers (2). However, as one can intuit, an airway of similar size or shape could be either stiff or compliant depending on the given wall properties of the structure. To date, static images of the pharyngeal airway, which are collected during wakefulness, have not been correlated with measurements of collapsibility during sleep. Currently, no strong evidence exists that anatomical factors can account for increased susceptibility of the male sex to pharyngeal collapse during sleep.

The functional properties of the upper airway have been quantitated by the degrees of static (pressure-area) and dynamic (pressure-flow) collapsibility during sleep (7, 8). Subtle changes in collapsibility can describe a continuous, but discrete, range of collapsibility that distinguishes between completely normal people who snore and patients with full-blown sleep apnea (8). In fact, pressure equivalent to a few centimeters of water separates the collapsing pressure of each of these groups. Because of the differences in technique, Pillar and colleagues did not quantitate the collapsing pressure (2). Nonetheless, their data convincingly demonstrate that the upper airway of men collapses more easily when stressed by a subtle upper airway resistive load. But we are again left with the question of why. Is there a direct hormonal effect on the upper airway, or are there other aspects of maleness or femaleness that contribute to an increased collapsibility and hence susceptibility to disease?

In general, there are minimal data concerning the relative effect of the sex hormones on collapsibility of the upper airway during sleep. What little is known comes from estimates of apnea severity with testosterone replacement or blockade in men or estrogen supplementation in postmenopausal women. In the case of hypogonadal men, testosterone produces a small but consistent increase in apnea (9, 10), and, in a case report, a concomitant rise in collapsibility (11). Androgen blockage, however, has no apparent effect (12). In women, the effect of estrogen replacement is more variable, with studies showing either a minimal decrease or no change in frequency of sleep apnea (13, 14). Thus, at most, the direct effects of sex hormones on sleep apnea severity appear minimal on the basis of current information.

Finally, it is possible that during sleep upper body obesity in men may impact more severely on upper airway function than lower body obesity in women (15). On the basis of upper airway CT scans, structural effects of adiposity in the neck region may directly compress the pharynx (7). Although there are no specific data on sex-related differences, it appears that the upper airway in obese men and women does not respond to standard mechanical maneuvers that are known to restore airway patency (15). Of particular note, research into the genetic basis of obesity may uncover factors linking obesity with alterations in ventilatory control. Specifically, evidence from the ob/ob mouse strongly suggests that the adipose-associated hormone leptin may be playing a particularly important protective role in the regulation of respiration, especially during sleep (16). Furthermore, the circulating levels of leptin are higher in women because subcutaneous fat (lower body obesity) produces more leptin than visceral fat (upper body obesity). It is possible that leptin or some other obesity-related factor could play a role in sex-related differences in breathing during sleep. Ironically, by probing differences between men and women, we may ultimately acknowledge the similarity of the sexes operating through common metabolic/hormonal pathways. In any case, future studies of sleep and breathing in men and women will need to pay particular attention to adiposity in all its forms.

Acknowledgments: Supported by grants HL57011 and HL59823 from the National Institutes of Health.

Supported by the Medical Research Council of Canada.

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