Background
Obstructive Sleep Apnea Syndrome (OSAS) is characterized by recurrent upper airway collapse and obstruction. Upper airway structure and function are believed to be primary determinants of the degree of upper airway collapsibility. Gender differences in upper airway structure and function are believed to explain the clear male predominance of OSAS in the general population.
In an investigation of the influence of gender on upper airway structure and function, James A. Rowley, Xusong Zhou, Isabelle Vergine, Mahdi A. Shkoukani, and M. Safwan Badr, all of the Sleep Research Laboratory, John D. Dingell Veterans Affairs Medical Center, and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan, conducted an investigation using two protocols involving men and women.
Upper airway collapsibility can be measured in several ways. Most researchers have focused on pharyngeal resistance, an indirect measure of upper airway caliber. Another measure is critical closing pressure (Pcrit), a concept based on modeling the upper airway as a simple collapsible tube. Although Pcrit has been compared between subjects with and without sleep apnea, there have been no reports on differences in Pcrit with gender.
Methodologies
In the study, these researchers examined two measures of upper airway mechanics that have been previously shown to characterize upper airway mechanics and function (pharyngeal resistance and Pcrit). In particular, they tested the hypothesis that (1) pharyngeal resistance during sleep would be larger in men and (2) Pcrit would be higher (i.e., the airway would be more susceptible to collapse) in men compared with women.
Protocol 1: Measurement of Upper Airway Resistance
- Data analysis: Measurements of upper airway resistance (Rua) were collected from studies performed on 33 men and 27 women. These subjects had either no sleep complaints or mild snoring on history. Studies in which apneas and hypopneas were demonstrated were excluded from analysis. In the majority of subjects (85 percent), breaths for analysis were chosen from a five-minute segment of stable stage 2 sleep. For the remaining subjects, a total of five-minute stable stage 2 sleep was chosen from multiple segments. Airflow and supraglottic pressure were recorded, and for each breath, a pressure-flow loop was generated, from which resistance was measured at two points. Resistance levels were computed and analyzed. For each subject, the percentage of inspiratory flow limitation (IFL) breaths was calculated as the number of IFL breaths divided by total breaths. Approximately 50-100 breaths were analyzed per subject.
- Statistical analysis: A simple t-test was used to compare men and women for age, body mass index (BMI), neck circumference (NC), resistance at a fixed flow of 0.2 l/s (RL), and resistance at peak airflow (Rpk). Multiple linear regression was utilized to determine whether gender, age, BMI, or NC predicted the resistance at 0.2 l/s and resistance at peak airflow during non-rapid eye movement (NREM) sleep. Because neither resistance at 0.2 l/s nor resistance at peak airflow was normally distributed, the research team first transformed the values to the natural logarithm. Multiple logistic regression analysis was used to determine whether gender, age, BMI, NC, or RL predicted whether a subject had >10 percent of the analyzed breaths showing flow limitation.
Protocol 2: Measurement of Pcrit
- Measurement: Measurement of Pcrit was performed in eight men and eight women recruited from the general population. The subjects were free of sleep complaints, including snoring. If, during the course of the study, the subject demonstrated sleep-disordered breathing, the study was terminated because only normal subjects were needed. In addition to the above measurements, pressure was also monitored at the nasal mask (Pn) in each subject. Pcrit measurements were performed in a manner similar to a previously published report on this measurement.
- Protocol: Patients were allowed to fall asleep breathing at atmospheric pressure. During periods of stable stage 2 sleep, Pn was abruptly reduced, maintained for two breaths, and then raised back to atmospheric. Complete airway collapse was achieved in all subjects.
Results Of Influence of Gender on Upper Airway Structure and Function
- Protocol 1: Measurement of Upper Airway Resistance
The study found no gender differences in upper airway resistance during stable stage 2 NREM sleep and corroborates recent work demonstrating no gender difference in the changes in upper airway resistance (Rua) between the awake state and NREM sleep. These findings agree with previous work by these researchers which found no gender difference in Rua during stage 2 NREM sleep.
- Protocol 2: Measurement of Pcrit
The study found no gender difference in Pcrit, which suggests that the upper airway of men is not more prone to collapse than that of women.
Conclusions
The gender difference in OSA prevalence could be secondary to differences in upper airway structure, function, or the neurochemical control of breathing. The evidence suggests there is no gender difference in upper airway size, whether measured directly by imaging methodologies or indirectly by Rua. Evidence also suggests that the degree of airway narrowing secondary to interventions such as negative pressure or resistance loading is not different between the genders. However, there remains a fundamental difference between the upper airway of men and women as evidenced by the increased susceptibility to the development of flow limitation and increased upper airway compliance in men compared with women.
The authors believe that different methodological approaches to upper airway function are measuring different aspects of upper airway function. Further research to explore the fundamental differences between various methodologies used to measure collapsibility and the implications of the differences for sleep-disordered breathing are therefore indicated.
Finally, because it has also been shown that men are more susceptible to hypocapnic hypopneas than women, further investigations into how the neurochemical control of ventilation interplays with mechanical and structural factors could be helpful in determining potential mechanisms for the gender prevalence difference in OSA.
A Unifying Hypothesis
The authors propose a hypothesis to explain the divergent findings regarding upper airway patency in men and women. First, nonneuromuscular factors -- primarily pharyngeal wall structures and properties -- are the likely dominant factor to explain within-breath changes in patency during breathing. They postulate that the anatomy of the male upper airway renders it more susceptible to within-breath narrowing under eupneic conditions. This postulate is supported by their unpublished findings that men have higher nasopharyngeal compliance compared with women during eupneic breathing and are more likely to develop inspiratory flow limitation in response to inspiratory resistive loading. It is also supported by a recent finding of increased soft tissue volume in the necks of men compared with women.
Second, neuromuscular factors are the dominant factors when the upper airway is challenged and these factors are not different between men and women. The similarity in Pcrit and the similarity in genioglossus response to inspiratory loading support this postulate. The authors emphasize that this interpretation is a speculation awaiting further experimental proof.
The authors also note that they found that an increased resistance predicted a lower likelihood of the presence of flow-limited breaths. This finding would indicate that a more narrow airway would be less prone to flow limitation, which is in contrast to the long-held assumption that a more narrow airway is a more easily collapsed airway.
Source: Journal of Applied Physiology (November 2001)
The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.
Journal
Journal of Applied Physiology