Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep

John D. Dingell Veterans Affairs Medical Center, and Division of Pulmonary and Critical Care Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Journal of Applied Physiology (Impact Factor: 3.06). 08/2000; 89(1):192-9.
Source: PubMed

ABSTRACT We hypothesized that a decreased susceptibility to the development of hypocapnic central apnea during non-rapid eye movement (NREM) sleep in women compared with men could be an explanation for the gender difference in the sleep apnea/hypopnea syndrome. We studied eight men (age 25-35 yr) and eight women in the midluteal phase of the menstrual cycle (age 21-43 yr); we repeated studies in six women during the midfollicular phase. Hypocapnia was induced via nasal mechanical ventilation for 3 min, with respiratory frequency matched to eupneic frequency. Tidal volume (VT) was increased between 110 and 200% of eupneic control. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea, depending on the magnitude of hypocapnia. Nadir minute ventilation in the recovery period was plotted against the change in end-tidal PCO(2) (PET(CO(2))) per trial; minute ventilation was given a value of 0 during central apnea. The apneic threshold was defined as the x-intercept of the linear regression line. In women, induction of a central apnea required an increase in VT to 155 +/- 29% (mean +/- SD) and a reduction of PET(CO(2)) by -4.72 +/- 0.57 Torr. In men, induction of a central apnea required an increase in VT to 142 +/- 13% and a reduction of PET(CO(2)) by -3.54 +/- 0.31 Torr (P = 0.002). There was no difference in the apneic threshold between the follicular and the luteal phase in women. Premenopausal women are less susceptible to hypocapnic disfacilitation during NREM sleep than men. This effect was not explained by progesterone. Preservation of ventilatory motor output during hypocapnia may explain the gender difference in sleep apnea.

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    • "The prevalence of obstructive sleep apnea (OSA) is more than three times greater in men than in women (Bixler et al., 2001; Young et al., 1993). The underlying phenotypical basis for this discrepancy is not well understood, although a number of broad gender-influenced physiological characteristics have been implicated, including: (1) obesity and fat distribution (Simpson et al., 2010), (2) upper airway anatomy and function (Brooks and Strohl, 1992; Mohsenin, 2001; Pillar et al., 2000), (3) ventilatory control (Jordan et al., 2005; Pillar et al., 2000), (4) hormonal status (Zhou et al., 2000) and (5) craniofacial anatomy (Lee et al., 1997). Some authors have invoked specific gender-based anatomical differences, including: (1) a longer and consequently more collapsible pharyngeal airway in men and (2) differences in mandible position (Malhotra et al., 2002; Mohsenin, 2003). "
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    ABSTRACT: Obstructive sleep apnea (OSA) is more common in men than women. Body size is greater in males (sexual dimorphism), but large body habitus is associated with OSA for both genders. We speculated that male–female phenotypical convergence (reduced sexual dimorphism via identical phenotype acquisition) occurs with OSA and tested hypotheses: (1) phenotypical features pathogenic for OSA differ between OSA and healthy subjects irrespective of gender; and (2) such characteristics exhibit phenotypical convergence. Utilizing an existing database, we calculated male–female (group average) ratios for eight anthropometric and 33 surface cephalometric variables from 104 Caucasian OSA patients [72 males; apnea–hypopnea index (events h−1): males: 42.3 ± 24.7 versus females: 42.6 ± 26.1 (P > 0.9)] and 85 Caucasian, healthy, non-OSA, community volunteers (36 males). Log-transformed data were analysed using a general linear model with post-hoc unpaired t-tests and significance at P < 0.0012 (Bonferroni multiple-comparison correction). OSA patients were older (56.9 ± 14.4 versus 38.0 ± 13.8 years), but there were no within-group gender-based age differences. All anthropometric variables (except height), plus cranial base width, mandibular breadth and retromandibular width diagonal were larger in gender-matched OSA versus healthy comparisons; thus satisfying hypothesis (1). Male–female ratios were mostly >1.0 across groups, but with no significant group × gender interactions no variable satisfied hypothesis (2). Thus, in this exploratory study, OSA patients had gender-common phenotypical differences to healthy subjects, but sexual dimorphism was preserved. Lack of complete phenotypical convergence may indicate gender-based critical phenotype-level attainment for OSA and/or gender-based OSA prevalence arises from factors other than those in this study.
    Journal of Sleep Research 08/2014; 24(1). DOI:10.1111/jsr.12205 · 3.35 Impact Factor
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    • "If carbon dioxide levels are beneath the chemoreflex threshold, central respiratory drive and chest wall respiratory muscle activity are eliminated culminating in a central apnea. The carbon dioxide level that demarcates the point at which ventilation is abolished has been deemed the apneic threshold (Dempsey, 2005; Xie et al., 2002; Zhou et al., 2000). The absence of central drive is also coupled to a reduction in upper airway muscle activity and ultimately to partial or complete closure of the upper airway (Badr et al., 1995, 1997; Badr and Kawak, 1996). "
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    ABSTRACT: This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea.
    Respiratory Physiology & Neurobiology 04/2013; 188(3). DOI:10.1016/j.resp.2013.04.010 · 1.97 Impact Factor
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    • "Behan and Wenninger (2008) showed that estrogens, progesterone and testosterone are involved in the central neural control of breathing, affecting cyclic fluctuations in ventilation during normal menstrual cycle. Additional evidence supporting the occurrence of gender-related differences in these respiratory patterns comes from studies that addressed differences between male and female subjects in the apneic threshold, carbon dioxide reserve and hypocapnic ventilatory response (Zhou et al., 2000), although these data are still controversial (Rowley et al., 2001, 2002; Tarbichi et al., 2003). At present, however, no study of acceptable size is available on gender-related differences in sleep-induced PB during exposure to high and very high altitude. "
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    ABSTRACT: High-altitude exposure is characterized by the appearance of periodic breathing during sleep. Only limited evidence is available, however, on the presence of gender-related differences in this breathing pattern. In 37 healthy subjects, 23 male and 14 female, we performed nocturnal cardio-respiratory monitoring in the following conditions: (1) sea level; (2) first/second night at an altitude of 3400 m; (3) first/second night at an altitude of 5400 m and after a 10 day sojourn at 5400 m. At sea level, a normal breathing pattern was observed in all subjects throughout the night. At 3400 m the apnea-hypopnea index was 40.3 ± 33.0 in males (central apneas 77.6%, central hypopneas 22.4%) and 2.4 ± 2.8 in females (central apneas 58.2%, central hypopneas 41.8%; P < 0.01). During the first recording at 5400 m, the apnea-hypopnea index was 87.5 ± 35.7 in males (central apneas 60.0%, central hypopneas 40.0%) and 41.1 ± 44.0 in females (central apneas 73.2%, central hypopneas 26.8%; P < 0.01), again with a higher frequency of central events in males as seen at lower altitude. Similar results were observed after 10 days. With increasing altitude, there was also a progressive reduction in respiratory cycle length during central apneas in males (26.9 ± 3.4 s at 3400 m and 22.6 ± 3.7 s at 5400 m). Females, who displayed a significant number of central apneas only at the highest reached altitude, were characterized by longer cycle length than males at similar altitude (30.1 ± 5.8 s at 5400 m). In conclusion, at high altitude, nocturnal periodic breathing affects males more than females. Females started to present a significant number of central sleep apneas only at the highest reached altitude. After 10 days at 5400 m gender differences in the apnea-hypopnea index similar to those observed after acute exposure were still observed, accompanied by differences in respiratory cycle length.
    Journal of Sleep Research 01/2013; 22(3). DOI:10.1111/jsr.12012 · 3.35 Impact Factor
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