Sexual function in male patients with obstructive sleep apnoea

Objective: Our objective was to investigate general and functional aspects of sexuality in male patients with a confirmed diagnosis of obstructive sleep apnoea (OSA) and compare the results with normative data. Materials and Methods: We investigated 308 male patients (age 30–69) admitted to a sleep laboratory and receiving a diagnosis of OSA, using questions drawn from two self‐administered questionnaires on sexuality [Fugl‐Meyer Life satisfaction checklist (LiSat) and Brief Sexual Function Inventory (BSFI)]. Results: We found that both general (Fugl‐Meyer LiSat) and functional (BSFI) aspects of sexuality were worse in patients with (untreated) OSA when compared with normative data. Both aspects were dependent on age, obesity, social factors and concomitant medication but not on the severity of OSA as reflected by the apnoea–hypopnoea index or subjective sleepiness. Conclusion: We conclude that although sexual dysfunction is more prevalent in OSA patients than in the general population, it is a complex problem relating more to age, obesity, social factors and comorbidity than to the severity of OSA. Please cite this paper as: Petersen M, Kristensen E, Berg S, Midgren B. Sexual function in male patients with obstructive sleep apnoea. The Clinical Respiratory Journal 2010; 4: 186–191.     

Neurocognitive function in obstructive sleep apnoea: A meta‐review

Adult obstructive sleep apnoea (OSA) is associated with cognitive dysfunction. While many review articles have attempted to summarize the evidence for this association, it remains difficult to determine which domains of cognition are affected by OSA. This is because of marked differences in the nature of these reviews (e.g. many are unsystematic) and the many different tasks and domains assessed. This paper addresses this issue by comparing the results of only systematic reviews or meta‐analyses assessing the effects of OSA on cognition, the relationship between OSA severity and cognition, and/or the effects of treatment on cognition in OSA. Electronic databases and hand‐searching were undertaken to select reviews that reported on these areas. We found 33 reviews; five reviews met predetermined, stringent selection criteria. The majority of reviews supported deficits in attention/vigilance, delayed long‐term visual and verbal memory, visuospatial/constructional abilities, and executive function in individuals with OSA. There is also general agreement that language ability and psychomotor function are unaffected by OSA. Data are equivocal for the effects of OSA on working memory, short‐term memory and global cognitive functioning. Attention/vigilance dysfunction appears to be associated with sleep fragmentation and global cognitive function with hypoxaemia. Continuous positive airway pressure treatment of OSA appears to improve executive dysfunction, delayed long‐term verbal and visual memory, attention/vigilance and global cognitive functioning. In order to improve our understanding of cognitive dysfunction in OSA, future research should pay particular attention to participant characteristics, measures of disease severity and choice of neuropsychological tests.     

Apnoeic–hypopnoeic episodes during obstructive sleep apnoea are associated with histological nonalcoholic steatohepatitis

Background: Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnoea are associated with metabolic syndrome and atherosclerotic heart disease. This study evaluates the potential association between the NAFLD subtypes and a number of polysomnographical (PSG) parameters. Methods: This study included patients undergoing bariatric surgery with extensive clinical and histological data for whom complete PSG data before surgery were also available. Excess alcohol intake and other causes of liver disease were excluded. Apnoea, hypopnoea and apnoea–hypopnoea index (AHI) were calculated as described previously. Results: In this study, a total of 101 patients [77 nonalcoholic steatohepatitis (NASH) and 22 non‐NASH controls] with PSG data were included (age 42.9 ± 11.4 years, body mass index 51.6 ± 9.5 kg/m², fasting serum glucose 117.4 ± 53.4 mg/dl, fasting serum triglycerides 171.3 ± 82.9 mg/dl, 58% hypertension and 33% diabetes mellitus). Subjects with histological NASH had significantly lower lowest desaturation (77 vs. 85%, P=0.006), lower mean nocturnal oxygen saturation (91 vs. 93%, P=0.05), higher AHI (35 vs. 22, P=0.03), higher respiratory disturbance index (46 vs. 21, P=0.02) and higher alanine aminotransferase/aspartate aminotransferase ratio (1.4 vs. 1.3, P=0.05) compared with non‐NASH controls. In multivariate analysis, the lowest desaturation (P=0.04) was independently associated with histological NASH. Lowest desaturation and mean nocturnal oxygen saturation were significantly lower in subjects with fibrosis (76 vs. 85%, P=0.004 and 90.4 vs. 93.0%, P=0.02). Conclusions: Our results suggest that the frequent nocturnal hypoxic episodes in NAFLD patients may be a risk factor for developing NASH. Additional studies are needed to study the effect of optimizing sleep apnoea management on the outcomes of patients with NAFLD.     

Endocrine effects of nasal continuous positive airway pressure in male patients with obstructive sleep apnoea

OBJECTIVE: Obstructive sleep apnoea (OSA) is a relatively common condition producing disabling somnolence and profound physiological responses to hypoxaemic episodes during sleep, including significant oscillations in blood pressure. This study aimed to provide controlled data on the interaction between OSA and endocrine axes to establish whether overrepresentation of pathology such as hypertension and hypogonadism in OSA subjects might have an endocrine basis. DESIGN, SETTING AND SUBJECTS: Parallel randomized sham placebo controlled 1-month trial of nasal continuous positive airway pressure (nCPAP) in 101 male subjects with OSA presenting to a respiratory sleep clinic. METHODS: Analysis of gonadotrophins, testosterone, sex hormone binding protein (SHBG), prolactin, cortisol, thyroid stimulating hormone (TSH), free thyroxine (free T4), insulin-like growth factor-1 (IGF-1), renin and aldosterone were performed at baseline and after 1 month's active or placebo nCPAP intervention. Quality of life questionnaire scoring was also recorded over the same time period. RESULTS: Testosterone and SHBG showed significant negative correlations with baseline OSA severity. Active treatment of OSA produced SHBG elevation and TSH reduction (P< or =0.03). Both groups showed an increase in aldosterone (P<0.001) and IGF-1 (P< or =0.03), associated with a large improvement in subjective quality of life scoring. CONCLUSIONS: These findings demonstrate significant changes in endocrine axes not previously reported in a placebo-controlled trial. OSA is a recognized reversible cause of testosterone reduction; SHBG suppression correlating to baseline OSA severity supports a diagnosis of secondary hypogonadism. Significant rises in aldosterone and IGF-1 on treatment coincide with increased physical activity and an improved quality of life score.     

Changes in respiratory disorder parameters during the night in patients with obstructive sleep apnoea

Background and objective: Patients with OSA frequently experience cardiovascular events, especially late at night. This phenomenon raises the possibility that respiratory disorders are progressively aggravated during the course of nocturnal sleep. To test this hypothesis, we investigated the changes in respiratory disorder parameters occurring during the night in patients with OSA, in the supine position and in all sleep positions. Methods: Thirty consecutive patients with OSA were enrolled in the study and categorized into those with moderate OSA (n = 12; AHI <40 events/h) and those with severe OSA (n = 18; AHI ≥40 events/h). To identify the time during the sleep period at which changes in respiratory disorder parameters were most pronounced, AHI, mean duration of apnoea and average SaO₂ were assessed during the early, middle and late segments of sleep, in the supine position and in all sleep positions. Results: AHI decreased significantly with time during the course of the total sleep period, and especially during non‐rapid eye movement (NREM) sleep. In the group with severe OSA, prolongation of the mean duration of apnoea and the decrease in average SaO₂ were also significant in the late segment of sleep in the supine position, especially during NREM sleep. Conclusions: In patients with severe OSA, there was progressive prolongation of the mean duration of apnoea late at night and this was associated with aggravation of hypoxia in the supine position during NREM sleep. This phenomenon may contribute to the remarkable rise in blood pressure early in the morning, possibly increasing the vulnerability of these patients to cardiovascular events.     

A resource of potential drug targets and strategic decision‐making for obstructive sleep apnoea pharmacotherapy

There is currently no pharmacotherapy for obstructive sleep apnoea (OSA) but there is no principled a priori reason why there should not be one. This review identifies a rational decision‐making strategy with the necessary logical underpinnings that any reasonable approach would be expected to navigate to develop a viable pharmacotherapy for OSA. The process first involves phenotyping an individual to quantify and characterize the critical predisposing factor(s) to their OSA pathogenesis and identify, a priori, if the patient is likely to benefit from a pharmacotherapy that targets those factors. We then identify rational strategies to manipulate those critical predisposing factor(s), and the barriers that have to be overcome for success of any OSA pharmacotherapy. A new analysis then identifies candidate drug targets to manipulate the upper airway motor circuitry for OSA pharmacotherapy. The first conclusion is that there are two general pharmacological approaches for OSA treatment that are of the most potential benefit and are practically realistic, one being fairly intuitive but the second perhaps less so. The second conclusion is that after identifying the critical physiological obstacles to OSA pharmacotherapy, there are current therapeutic targets of high interest for future development. The final analysis provides a tabulated resource of ‘druggable’ targets that are relatively restricted to the circuitry controlling the upper airway musculature, with these candidate targets being of high priority for screening and further study. We also emphasize that a pharmacotherapy may not cure OSA per se, but may still be a useful adjunct to improve the effectiveness of, and adherence to, other treatment mainstays.     

P4 medicine approach to obstructive sleep apnoea

P4 medicine is an evolving approach to personalized medicine. The four Ps offer a means to: Predict who will develop disease and co‐morbidities; Prevent rather than react to disease; Personalize diagnosis and treatment; have patients Participate in their own care. P4 medicine is very applicable to obstructive sleep apnoea (OSA) because each OSA patient has a different pathway to disease and its consequences. OSA has both structural and physiological mechanisms with different clinical subgroups, different molecular profiles and different consequences. This may explain why there are different responses to alternative therapies, such as intraoral devices and hypoglossal nerve stimulation therapy. Currently, technology facilitates patients to participate in their own care from screening for OSA (snoring and apnoea apps) to monitoring response to therapy (sleep monitoring, blood pressure, oxygen saturation and heart rate) as well as monitoring their own continuous positive airway pressure (CPAP) compliance. We present a conceptual framework that provides the basis for a new, P4 medicine approach to OSA and should be considered more in depth: predict and prevent those at high risk for OSA and consequences, personalize the diagnosis and treatment of OSA and build in patient participation to manage OSA.     

Respiratory effort during sleep and the rate of prevalent type 2 diabetes in obstructive sleep apnoea

Aim

To determine the association between total sleep time (TST) spent in increased respiratory effort (RE) and the prevalence of type 2 diabetes in a large cohort of individuals with suspected obstructive sleep apnoea (OSA) referred for in-laboratory polysomnography (PSG).

Materials and Methods

We conducted a retrospective cross-sectional study using the clinical data of 1128 patients. Non-invasive measurements of RE were derived from the sleep mandibular jaw movements (MJM) bio-signal. An explainable machine-learning model was built to predict prevalent type 2 diabetes from clinical data, standard PSG indices, and MJM-derived parameters (including the proportion of TST spent with increased respiratory effort [REMOV [%TST]).

Results

Original data were randomly assigned to training (n = 853) and validation (n = 275) subsets. The classification model based on 18 input features including REMOV showed good performance for predicting prevalent type 2 diabetes (sensitivity = 0.81, specificity = 0.89). Post hoc interpretation using the Shapley additive explanation method found that a high value of REMOV was the most important risk factor associated with type 2 diabetes after traditional clinical variables (age, sex, body mass index), and ahead of standard PSG metrics including the apnoea-hypopnea and oxygen desaturation indices.

Conclusions

These findings show for the first time that the proportion of sleep time spent in increased RE (assessed through MJM measurements) is an important predictor of the association with type 2 diabetes in individuals with OSA.     

The central motor conductivity of genioglossus in obstructive sleep apnoea

Background and objective: During wakefulness, the electromyography (EMG) activities of upper airway dilator muscles are higher in OSA syndrome (OSAS) patients than those in normal subjects. This is believed to be related to central compensatory mechanisms. This study aimed to assess the central motor conductivity of genioglossus (GG) during wakefulness and to evaluate the compensatory site in OSAS patients. Methods: Twelve OSAS patients and 12 normal subjects were recruited to record motor evoked potential (MEP) of GG to transcranial magnetic stimulation applied at dominant‐sided anterolateral area and GG response to magnetic stimulation at the third cervical level. Stimuli were delivered at the end of expiration and inspiration respectively. The central motor conduction time (CMCT) was calculated by the latency difference between cortical and cervical stimulations. Results: The MEP latency and CMCT of GG in OSAS patients were shorter than those in normal subjects at the end of expiration (MEP latency: 6.08 ± 2.06 ms and 8.24 ± 2.66 ms, respectively, P < 0.05; CMCT: 2.41 ± 1.20 ms and 3.58 ± 1.53 ms, respectively, P < 0.05). However, only in normal subjects, GG MEP latency and CMCT showed significant decrease from the end of expiration to the end of inspiration. GG CMCT of OSAS patients at the end of expiration was closely correlated with AHI (r = ?0.797, P = 0.002), the nadir oxygen saturation (r = 0.76, P = 0.003) and the longest apnoea time (r = ?0.68, P = 0.02). Conclusions: OSAS patients have an increased central motor conductivity of GG than normal subjects. Furthermore, this increased central motor conductivity of GG is related to the severity of OSAS.     

Improvement of sleep apnoea due to acromegaly during short-term treatment with octreotide

Abstract. Two acromegalic patients suffering from severe obstructive sleep apnoea syndrome were treated with the long-acting somatostatin analogue octreotide. Daytime sleepiness and fatigue improved within a few days. Repeat sleep studies performed after octreotide treatment revealed more confluent sleep with a shorter duration of sleep apnoea. Nocturnal hypoxaemia improved in one patient. Octreotide might be an effective noninvasive treatment for sleep apnoea of acromegaly.     

Predicting optimal continuous positive airway pressure in Japanese patients with obstructive sleep apnoea syndrome

Background and objective: Several algorithms that predict the optimal CPAP have been developed for Caucasian patients with OSA syndrome, but these algorithms do not allow for racial differences in craniofacial anatomy. We investigated whether an equation that included data on craniofacial structure, physique and severity of OSA could more accurately predict the optimal CPAP for Japanese patients with OSA syndrome. Methods: In 170 Japanese patients with OSA syndrome, the optimal CPAP was determined by manual titration during polysomnography. An equation predicting the optimal pressure was derived from anthropometric, polysomnographic and cephalometric data. This equation was validated in another 110 Japanese patients with OSA syndrome. Results: Stepwise multiple regression analysis identified AHI, BMI, mean SaO₂ and a cephalometric parameter: the angle between a line from point B to the menton (Me) and a line from Me to the hyoid bone (H) (BMeH), as independent predictors of optimal CPAP. The following equation was constructed to predict the optimal CPAP: 27.78 + (0.041 × BMeH) + (0.141 × BMI) + (0.040 × AHI) ? (0.312 × mean SaO₂). This equation accounted for 47% of the variance in optimal pressure (R² = 0.47, P < 0.0001). The measured optimal pressure and the pressure calculated using this equation were very similar in the other 110 patients with OSA syndrome (9.5 ± 3.0 and 9.2 ± 2.1 cmH₂O, respectively). Conclusion: Optimal CPAP was more accurately predicted by combining a cephalometric parameter with BMI and polysomnographic data in Japanese patients with OSA, suggesting that craniofacial structure may be important in the pathogenesis of OSA syndrome among Asians.