Sex differences in sleep disordered breathing in adults

Lozo, Tijana; Komnenov, Dragana; Badr, M. Safwan; Mateika, Jason H.

doi:10.1016/j.resp.2016.11.001

Cited by 48 publications

(26 citation statements)

References 119 publications

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“…‘On‐protocol’ analyses yielded similar conclusions; therefore, only results of intent‐to‐treat analyses are reported. Given that sex differences have been observed in chemoreflex sensitivity (Lozo, Komnenov, Badr, & Mateika, ), hypoxic vasodilatation (Casey, Shepherd, & Joyner, ) and sympathetic regulation of vascular tone (Hinojosa‐Laborde, Chapa, Lange, & Haywood, ), the possibility of differential sex‐specific effects was examined using an exploratory analysis, adjusted for CPAP adherence.…”

Section: Methodsmentioning

confidence: 99%

Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea

Morgan

Teodorescu

Pegelow

et al. 2018

Experimental Physiology

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Chemoreflex sensitization produced by chronic intermittent hypoxia in rats is attenuated by angiotensin II type 1 receptor (AT R) blockade. Both AT R blockade and xanthine oxidase inhibition ameliorate chronic intermittent hypoxia-induced endothelial dysfunction. We hypothesized that treatment with losartan and allopurinol would reduce chemoreflex sensitivity and improve hypoxic vasodilatation in patients with obstructive sleep apnoea. Eighty-six hypertensive patients with apnoea-hypopnoea index ≥25 events h and no other cardiovascular, pulmonary, renal or metabolic disease were randomly assigned to receive allopurinol, losartan or placebo for 6 weeks. Treatment with other medications and/or continuous positive airway pressure remained unchanged. Tests of chemoreflex sensitivity and hypoxic vasodilatation were performed during wakefulness before and after treatment. Ventilation (pneumotachography), muscle sympathetic nerve activity (microneurography), heart rate (electrocardiography), arterial oxygen saturation (pulse oximetry), blood pressure (sphygmomanometry), forearm blood flow (venous occlusion plethysmography) and cerebral flow velocity (transcranial Doppler ultrasound) were measured during eupnoeic breathing and graded reductions in inspired O tension. Losartan and allopurinol lowered arterial pressure measured during eupnoeic breathing and exposure to acute hypoxia. Neither drug altered the slopes of ventilatory, sympathetic or cardiovascular responses to acute hypoxia. We conclude that losartan and allopurinol are viable pharmacotherapeutic adjuncts for achieving blood pressure control in hypertensive obstructive sleep apnoea patients, even those who are adequately treated with continuous positive airway pressure.

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Section: Methodsmentioning

confidence: 99%

Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea

Morgan

Teodorescu

Pegelow

et al. 2018

Experimental Physiology

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“…The idea that progesterone could be used for the treatment of apnoea in the newborn is based on the fact that in women after menopause, or in men, it significantly decreases sleep-disordered breathing (Boukari et al 2017;Lozo et al 2017), and increases ventilation in adult subjects (including humans) in normoxic, hypoxic and hypercapnic conditions (Behan & Kinkead, 2011;Boukari et al 2017;Lozo et al 2017). However, we have obtained contradictory data in newborn rats, and the respiratory function of progesterone during postnatal development remains to be elucidated fully.…”

Section: Introductionmentioning

confidence: 96%

“…; Lozo et al . ). However, we have obtained contradictory data in newborn rats, and the respiratory function of progesterone during postnatal development remains to be elucidated fully.…”

Section: Introductionmentioning

confidence: 97%

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Respiratory regulation by steroids in newborn rats: a sex‐specific balance between allopregnanolone and progesterone receptors

Joseph

Uppari

Kouchi

et al. 2018

Experimental Physiology

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What is the central question of this study? What are the contributions of allopregnanolone, the neuroactive metabolite of progesterone, and nuclear (nPR) and membrane (mPR) progesterone receptors to the respiratory effect of progesterone in newborn rats? What is the main finding and its importance? Acute progesterone injection increases the apnoea frequency, whereas finasteride (which blocks the conversion of progesterone to allopregnanolone) reduces apnoea frequency. An nPR agonist decreases apnoea frequency in males and an mPR agonist decreases apnoea frequency in males and females. Chronic injection of progesterone decreases the frequency of apnoea more efficiently in males than in females. We tested the hypothesis that the effects of progesterone on apnoea frequency in newborn rats are the result of a balance between its neuroactive metabolite, allopregnanolone (GABA receptor modulator), and progesterone receptors. We used male and female rats between 10 and 12 days of age and recorded respiratory and metabolic parameters (whole-body plethysmography), and assessed the frequency and duration of apnoeas in normoxia. We tested the effects of a single injection of progesterone (4 mg kg , i.p.), finasteride (10 mg kg , i.p.; a 5α-reductase antagonist, which blocks the conversion of progesterone to allopregnanolone), finasteride plus progesterone, or agonists of the nuclear or membrane progesterone receptors (R5020 or Org-od-02-0, 4 mg kg ). To test the hypothesis that chronic exposure to progesterone reduces the frequency of apnoeas, we used male and female rats treated daily with progesterone between postnatal days 3 and 12. The acute injection of progesterone reduced minute ventilation and metabolic rate and increased the frequency of apnoeas. Finasteride decreased the frequency of apnoeas, and finasteride plus progesterone did not increase apnoea frequency but decreased minute ventilation in female rats. Although R5020 decreased apnoea frequency only in males, Org-od-02-0 decreased apnoea frequency in males and females and decreased respiratory frequency in females. Chronic progesterone treatment reduced apnoea frequency more efficiently in males than in females, but in females (not in males) an acute injection of caffeine (the gold standard for the treatment of apnoea in preterm neonates) further reduced apnoea frequency. Apnoea frequency in newborn rats is, in part, determined by a sex-specific balance between allopregnanolone, GABA receptors and progesterone receptors.

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“…Heritable differences in craniofacial structures have been shown between OSA patients and controls [22,23], but sophisticated analyses may be necessary to identify heritable traits in a complex disease such as OSA [21]. Finally, OSA shows major sex- [24] and age-related [25] differences in clinical and polysomnographic presentation, further complicating the overall clinical picture.…”

Section: Introductionmentioning

confidence: 99%

Personalised medicine in sleep respiratory disorders: focus on obstructive sleep apnoea diagnosis and treatment

et al. 2017

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In all fields of medicine, major efforts are currently dedicated to improve the clinical, physiological and therapeutic understanding of disease, and obstructive sleep apnoea (OSA) is no exception. The personalised medicine approach is relevant for OSA, given its complex pathophysiology and variable clinical presentation, the interactions with comorbid conditions and its possible contribution to poor outcomes. Treatment with continuous positive airway pressure (CPAP) is effective, but CPAP is poorly tolerated or not accepted in a considerable proportion of OSA patients. This review summarises the available studies on the physiological phenotypes of upper airway response to obstruction during sleep, and the clinical presentations of OSA ( phenotypes and clusters) with a special focus on our changing attitudes towards approaches to treatment. Such major efforts are likely to change and expand treatment options for OSA beyond the most common current choices (i.e. CPAP, mandibular advancement devices, positional treatment, lifestyle changes or upper airway surgery). More importantly, treatment for OSA may become more effective, being tailored to each patient's need.

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Sex differences in sleep disordered breathing in adults

Cited by 48 publications

References 119 publications

Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea

Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea

Respiratory regulation by steroids in newborn rats: a sex‐specific balance between allopregnanolone and progesterone receptors

Personalised medicine in sleep respiratory disorders: focus on obstructive sleep apnoea diagnosis and treatment

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