Oxidative stress and inflammatory markers in the exhaled breath condensate of children with OSA

Introduction

Obstructive sleep apnea (OSA) in children has been associated with systemic inflammation and oxidative stress. Limited evidence indicates that pediatric OSA is associated with oxidative stress and inflammation in the airway.

Objective

The objective of this study is to assess the hypothesis that levels of oxidative stress and inflammatory markers in the exhaled breath condensate (EBC) of children with OSA are higher than those of control subjects.

Methods

Participants were children with OSA and control subjects who underwent overnight polysomnography. Morning levels of hydrogen peroxide (H₂O₂) and sum of nitrite and nitrate (NO _x ) in EBC of participants were measured.

Results

Twelve subjects with moderate-to-severe OSA (mean age?±?standard deviation: 6.3?±?1.7?years; apnea?Chypopnea index??AHI, 13.6?±?10.1 episodes/h), 22 subjects with mild OSA (6.7?±?2.1?years; AHI, 2.8?±?1 episodes/h) and 16 control participants (7.7?±?2.4?years; AHI, 0.6?±?0.3 episodes/h) were recruited. Children with moderate-to severe OSA had higher log-transformed H₂O₂ concentrations in EBC compared to subjects with mild OSA, or to control participants: 0.4?±?1.1 versus ?0.9?±?1.3 (p?=?0.015), or versus ?1.2?±?1.2 (p?=?0.003), respectively. AHI and % sleep time with oxygen saturation of hemoglobin <95% were significant predictors of log-transformed H₂O₂ after adjustment by age and body mass index z score (p? x levels.

Conclusions

Children with moderate-to-severe OSA have increased H₂O₂ levels in morning EBC, an indirect index of altered redox status in the respiratory tract.     

CRP evolution pattern in CPAP-treated obstructive sleep apnea patients. Does gender play a role?

Background??aim

C-reactive protein (CRP) is directly implicated in atherogenesis and associated cardiovascular morbidity in patients with obstructive sleep apnea (OSA). Effective continuous positive airway pressure (CPAP) treatment has been shown to gradually decrease CRP levels and thus consequently improve disease-related cardiovascular morbidity. However, the influence of gender on the CRP evolution pattern has never been assessed before. The aim of our study was to investigate possible gender differences in CRP evolution in OSA patients 3 and 6?months after the start of effective CPAP treatment.

Methods

The study population consisted of 436 patients (252 males/184 females) with newly diagnosed moderate to severe OSA and good CPAP compliance assessed by a thorough follow up. High-sensitivity C-reactive protein (hs-CRP) was assessed before CPAP initiation and at the third and sixth month of the follow-up period.

Results

C-reactive protein values showed a statistically significant decrease at the third and sixth month of CPAP therapy [initial values 0.79?±?0.65?mg/dL versus 0.70?±?0.52?mg/dL (p?p?p?p?>?0.05). After 6?months?? treatment, CRP decreased significantly in both genders (males from 0.74?±?0.53?mg/dL to 0.28?±?0.32?mg/dL, p?p?Conclusion Our results suggest a delay in the normalization of CRP levels in females despite effective CPAP treatment. A time period of at least 6?months appeared to be required in women in order to reduce CRP levels and consequent cardiovascular risk. In contrast, CPAP??s protective role in males is achieved at an earlier time point. Gender-related hormonal and genetic factors may influence the above CRP evolution pattern.     

The effect of continuous positive airway pressure therapy on blood pressure and arterial stiffness in hypertensive patients with obstructive sleep apnea

Aim

We aimed to evaluate the effect of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) and arterial stiffness in hypertensive patients with obstructive sleep apnea (OSA).

Patients and methods

We studied 38 hypertensive patients who suffered from severe OSA. Ambulatory BP measurement was performed at baseline and after at least 3 months of uninterrupted CPAP therapy. In 19 of these patients, we also measured pulse wave velocity (PWV) at baseline, after the first night of CPAP therapy and at 3 months. Fifteen normotensive subjects without OSA comprised the control group.

Results

CPAP therapy reduced systolic BP from 141.5?±?12.1 to 133.5?±?9.7 mmHg (p?=?0.007) and diastolic BP from 87.8?±?6.8 to 83?±?5.4 mmHg (p?=?0.004). CPAP also reduced the PWV from 8.81?±?1.4 to 8.18?±?1 m/s after the first night of CPAP therapy (p?=?0.003) and to 7.37?±?1 m/s at 3 months (p?=?0.007).

Conclusions

To the best of our knowledge, this is the first study demonstrating that CPAP therapy in hypertensive patients with OSA improves arterial stiffness from the first night and that this favorable effect is maintained for at least 3 months of CPAP use. A reduction in BP was also observed, even though BP control was not always achieved.     

Levels of thioredoxin are related to the severity of obstructive sleep apnea: based on oxidative stress concept

Background

Oxidative stress is a typical feature of obstructive sleep apnea (OSA). Thioredoxin (TRX), as one of the oxidative stress biomarkers, is a potent protein disulfide reductase in antioxidant defense. Our study is designed to test whether thioredoxin could assess the severity of OSA.

Methods

Sixty-three adults suspected of having OSA were included in this study and were divided into four groups based on the results of polysomnography (PSG): control, mild, moderate, and severe. Subjects with chronic medical diseases (with the exception of essential hypertension) or taking any antioxidant medication were excluded. Blood samples were obtained within an hour after the overnight PSG test. Plasma TRX levels were detected by enzyme-linked immunosorbent assay.

Results

The plasma TRX level in severe group was obviously increased (8.62?±?2.14, 13.33?±?5.60, 14.71?±?5.53, and 16.10?±?7.34 ng/ml; p?<?0.05). The TRX positively related to AHI (r?=?0.313; p?<?0.05), while negatively related to the lowest O₂ saturation (r?=?0.266; p?<?0.037). The OSA patients associated with hypertension showed elevated TRX level (17.70?±?6.98 vs. 13.43?±?5.83 ng/ml; t?=?2.434, p?<?0.018). The cutoff value of TRX for identifying OSA was 9.39 ng/ml (sensitivity 91 %, specificity 78 %), and its cutoff value for differentiating moderate–severe OSA from mild OSA was 11.79 ng/ml (sensitivity 75 %, specificity 65 %).

Conclusion

These results suggest that plasma TRX level is associated with the severity of OSA. Therefore, TRX may be used as a severity indicator of OSA.     

Clinical and polysomnographic findings of patients with large goiters

Introduction

Goiters cause a series of compressive symptoms, including dyspnea and dysphagia. There have been reports of the coexistence of this syndrome with obstructive sleep apnea (OSA). The objective of this study was to evaluate the prevalence of OSA in a group of patients with goiters.

Methods

Twenty-four patients with a mean age of 52.7?±?12.7 years, including five males (20.8 %) and 19 (79.2 %) females, who were diagnosed with euthyroid goiters with volumes exceeding 100 ml were consecutively selected. The protocol consisted of sleep questionnaires, physical examinations, and baseline polysomnography measurements. Patients were divided into two groups, OSA and NOSA (no OSA), and all findings were compared between the two groups.

Results

Of the studied patients, 70.8 % had OSA (p?=?0.004). Regarding clinical parameters, age (p?=?0.001), Epworth Sleepiness Scale scores (p?=?0.039) and complaints of habitual snoring (p?<?0.001) had higher values in the OSA group. Regarding physical examination parameters, body mass index (p?=?0.012), neck circumference (p?=?0.009) and the presence of tracheal compression (p?=?0.021) had higher values in the OSA group. The polysomnographic parameters that were significantly different between the two groups were the greater apnea and hypopnea index per hour of sleep (p?<?0.001) and the lower minimum oxyhemoglobin saturation in the OSA group (p?=?0.011).

Conclusions

There is a high prevalence of OSA in patients with goiters. The main findings that were associated with the presence of OSA are known clinical predictors of OSA and the presence of tracheal compression.     

Reverse atrial electrical remodelling induced by continuous positive airway pressure in patients with severe obstructive sleep apnoea

Background

Obstructive sleep apnoea (OSA) is associated with cardiovascular morbidity and mortality, including atrial arrhythmias. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; its impact on atrial electrical remodelling has not been fully investigated. Signal-averaged p-wave (SAPW) duration is an accepted marker for atrial electrical remodelling.

Objective

The objective of this study is to determine whether CPAP induces reverse atrial electrical remodelling in patients with severe OSA.

Methods

Consecutive patients attending the Sleep Disorder Clinic at Kingston General Hospital underwent full polysomnography. OSA-negative controls and severe OSA were defined as apnoea–hypopnea index (AHI)?<?5 events/hour and AHI?≥?30 events/hour, respectively. SAPW duration was determined at baseline and after 4–6 weeks of CPAP in severe OSA patients or without intervention controls.

Results

Nineteen severe OSA patients and 10 controls were included in the analysis. Mean AHI and minimum oxygen saturation were 41.4?±?10.1 events/hour and 80.5?±?6.5 % in severe OSA patients and 2.8?±?1.2 events/hour and 91.4?±?2.1 % in controls. At baseline, severe OSA patients had a greater SAPW duration than controls (131.9?±?10.4 vs 122.8?±?10.5 ms; p?=?0.02). After CPAP, there was a significant reduction of SAPW duration in severe OSA patients (131.9?±?10.4 to 126.2?±?8.8 ms; p?<?0.001), while SAPW duration did not change after 4–6 weeks in controls.

Conclusion

CPAP induced reverse atrial electrical remodelling in patients with severe OSA as represented by a significant reduction in SAPW duration.     

P wave duration and dispersion in Holter electrocardiography of patients with obstructive sleep apnea

Purpose

The underlying mechanisms of the association between obstructive sleep apnea (OSA) and atrial fibrillation (AF) remained unclear. We investigated P wave parameters as indicators of atrial conduction status among OSA patients.

Methods

We studied 42 untreated OSA patients, categorized into mild (6), moderate (18), and severe (18) OSA based on the apnea/hypopnea index (AHI) and 18 healthy controls. Twenty-four-hour Holter electrocardiography was applied to measure P wave parameters including P wave duration and P wave dispersion; difference between the maximum (P-max) and minimum (P-min) measured P wave duration.

Results

Mean P wave duration ranged from 110.2?±?9.3 ms in mild OSA patients to 121.1?±?15.4 ms in severe OSA patients and was 113.4?±?10.0 ms in controls with no significant difference among the groups, P?=?0.281. P wave dispersion and P-max were significantly longer in those with moderate OSA (68.0?±?9.3 and 154.2?±?9.3 ms) and those with severe OSA (71.6?±?13.7 and 157.2?±?13.3 ms) than controls (52.6?±?15.3 and 142.1?±?15.4 ms), P?r?=?0.407, P?=?0.012) and P wave dispersion (r?=?0.431, P?=?0.008). With linear regression analysis controlling for age, gender, and BMI, the AHI was independently associated with P wave dispersion (β?=?0.482, P?=?0.002).

Conclusions

Using Holter monitoring for measurement of P wave parameters, this study showed an association of OSA with prolonged P-max and P wave dispersion. These results indicate that patients with OSA have disturbances in atrial conduction associated with OSA severity. Repeating this study in a larger sample of patients is warranted.     

Eicosapentaenoic Acid Combined with Optimal Statin Therapy Improves Endothelial Dysfunction in Patients with Coronary Artery Disease

Purpose

Eicosapentaenoic acid (EPA) has been reported to augment endothelial function and improve clinical outcomes in patients with coronary artery disease (CAD). The purpose of this study was to determine whether EPA could improve residual endothelial dysfunction despite adequate lipid-lowering with statin in CAD patients.

Methods

Eighty patients with established CAD, who had been on statin treatment and had serum low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dl, were randomly assigned to receive either 1,800 mg of EPA daily plus statin (EPA group, n?=?40) or statin alone (Control group, n?=?40). Lipid profiles and flow-mediated dilation (FMD) were assessed just before and after more than 3 months of treatment in both groups. Only patients who had impaired FMD (<6 %) before randomization were enrolled.

Results

After treatment for 5.2?±?1.7 months, the EPA group showed a significant increase in the serum concentration of EPA and EPA to arachidonic acid (AA) (EPA/AA) ratio (62.5?±?38.1 to 159.8?±?53.8 μg/ml, 0.45?±?0.34 to 1.20?±?0.55, p?<?0.01 for both). In the EPA group, serum triglycerides significantly decreased (150.7?±?92.9 to 119.3?±?60.7 mg/dl, p?=?0.02), whereas no significant change was seen in the Control group. FMD, the primary study endpoint, showed a significant improvement in the EPA group (2.6?±?1.6 % to 3.2?±?1.6 %, p?=?0.02), whereas no significant change was observed in the Control group (2.7?±?1.6 % to 2.4?±?1.7 %, p?=?0.29).

Conclusions

EPA improved endothelial function and impaired FMD in patients with established CAD who were on optimal statin therapy.     

Circulating Survivin Levels in Obstructive Sleep Apnoea

Introduction

Obstructive sleep apnoea (OSA) is characterised by a low-grade systemic and airway inflammation; however, the regulatory mechanisms of inflammation are poorly explored. Survivin (Birc5) is an anti-apoptotic protein which inhibits Type 1 inflammation; however, this molecule has not been investigated in OSA.

Methods

Forty-five patients with OSA and 31 non-OSA control subjects were involved. Venous blood was collected for plasma survivin measurements before and after diagnostic overnight polysomnography. Plasma survivin levels were compared between the two groups and correlated to OSA severity and comorbidities.

Results

Plasma survivin levels were lower in OSA in the evening (27.6?±?89.9 vs. 108.3?±?161.2 pg/ml, p?<?0.01) and in the morning (17.4?±?48.6 vs. 36.4?±?69.2 pg/ml, p?=?0.02) compared to the control group. This OSA-related decrease was also present when only the non-obese patients were analysed. Significant indirect relationships were observed between plasma survivin levels and measures of OSA severity such as the apnoea–hypopnoea index (r?=???0.45) or oxygen desaturation index (r?=???0.40, both p?<?0.01); however, when adjusting to BMI, these became insignificant (p?>?0.05). Low plasma survivin concentrations were associated with high BMI (r?=???0.35), high CRP (r?=???0.31), low HDL cholesterol (r?=?0.24) and high triglyceride levels (r?=???0.24, all p?<?0.05).

Conclusion

Plasma survivin levels are reduced in OSA, relate to disease severity, and are associated with high CRP levels. This suggests an impaired immunoregulation in this disorder which needs to be studied in further detail.

     

Effects of calcium–vitamin D co-supplementation on glycaemic control,inflammation and oxidative stress in gestational diabetes: a randomised placebo-controlled trial

Aims/hypothesis

This study was designed to assess the effects of calcium and vitamin D supplementation on the metabolic status of pregnant women with gestational diabetes mellitus (GDM).

Methods

This randomised placebo-controlled trial was performed at maternity clinics affiliated to Kashan University of Medical Sciences, Kashan, Iran. Participants were 56 women with GDM at 24–28 weeks’ gestation (18 to 40 years of age). Subjects were randomly assigned to receive calcium plus vitamin D supplements or placebo. All study participants were blinded to group assignment. Individuals in the calcium–vitamin D group (n?=?28) received 1,000 mg calcium per day and a 50,000 U vitamin D₃ pearl twice during the study (at study baseline and on day 21 of the intervention), and those in the placebo group (n?=?28) received two placebos at the mentioned times. Fasting blood samples were taken at study baseline and after 6 weeks of intervention.

Results

The study was completed by 51 participants (calcium–vitamin D n?=?25, placebo n?=?26). However, as the analysis was based on an intention-to-treat approach, all 56 women with GDM (28 in each group) were included in the final analysis. After the administration of calcium plus vitamin D supplements, we observed a significant reduction in fasting plasma glucose (?0.89?±?0.69 vs +0.26?±?0.92 mmol/l, p?p?=?0.02) and HOMA-IR (?0.91?±?1.18 vs +0.63?±?2.01, p?=?0.001) and a significant increase in QUICKI (+0.02?±?0.03 vs ?0.002?±?0.02, p?=?0.003) compared with placebo. In addition, a significant reduction in serum LDL-cholesterol (?0.23?±?0.79 vs +0.26?±?0.74 mmol/l, p?=?0.02) and total cholesterol: HDL-cholesterol ratio (?0.49?±?1.09 vs +0.18?±?0.37, p?=?0.003) and a significant elevation in HDL-cholesterol levels (+0.15?±?0.25 vs ?0.02?±?0.24 mmol/l, p?=?0.01) was seen after intervention in the calcium–vitamin D group compared with placebo. In addition, calcium plus vitamin D supplementation resulted in a significant increase in GSH (+51.14?±?131.64 vs ?47.27?±?203.63 μmol/l, p?=?0.03) and prevented a rise in MDA levels (+0.06?±?0.66 vs +0.93?±?2.00 μmol/l, p?=?0.03) compared with placebo.

Conclusions/interpretation

Calcium plus vitamin D supplementation in women with GDM had beneficial effects on their metabolic profile.

Trial registration

www.irct.ir IRCT201311205623N11

Funding

The study was supported by a grant (no. 92110) from Kashan University of Medical Sciences.     

Statin-Induced Immunomodulation Alters Peripheral Invariant Natural Killer T-cell Prevalence in Hyperlipidemic Patients

Purpose

To assess the difference in the prevalence of invariant Natural Killer T (iNKT) lymphocytes between hyperlipidemic and control individuals and to evaluate changes in iNKT cell levels after 6?months lipid lowering therapy.

Methods

A total of 77 hyperlipidemic individuals (54?±?5?years) were assigned to simvastatin 40?mg or ezetimibe 10?mg daily for 6?months. Fifty individuals with normal cholesterol levels were used as control. iNKT cells were measured by flow cytometry in peripheral blood.

Results

Patients with hypercholesterolemia had significantly lower iNKT cell levels (percentage on the lymphocyte population) compared to control group (0.16?±?0.04% vs 0.39?±?0.08%, p?=?0.03). iNKT cells significantly increased after 6?months treatment with simvastatin (from 0.15?±?0.04% to 0.28?±?0.11%, p?=?0.03) but not with ezetimibe (from 0.16?±?0.05% to 0.17?±?0.06%, p?=?0.55). Simvastatin treatment did not alter the activation status of iNKT cells as measured by HLA-DR expression. Changes of iNKT cells were independent from changes in total (r ²?=?0.009, p?=?0.76) or LDL cholesterol (r ²?=?0.008, p?=?0.78) reached by simvastatin.

Conclusions

Hyperlipidemic patients have reduced numbers of iNKT in peripheral circulation compared to individuals with normal cholesterol levels. Their number is increasing after long term administration of simvastatin 40?mg but not after ezetimibe.     

Obstructive sleep apnea is common in patients with interstitial lung disease

Purpose

The incidence of obstructive sleep apnea (OSA) in interstitial lung disease (ILD) has been reported at different frequencies in several studies. The aims of our study were to evaluate the frequency of OSA in ILD and to analyze the relationship between polysomnography (PSG) findings and pulmonary function, disease severity, parenchymal involvement, and Epworth Sleepiness Scale (ESS) scores.

Methods

ILD patients with parenchymal involvement were evaluated. The disease severity was assessed using an index consisting of body mass index (BMI), carbon monoxide diffusion capacity, the Modified Medical Research Council dyspnea scale, and the 6-min walking distance. All of the patients had lung function, chest X-ray, PSG, ESS scoring, and an upper airway examination. Patients with a BMI?≥?30 or significant upper airway pathologies were excluded.

Results

Of 62 patients, 50 patients comprised the study group (14 male, 36 female; mean age 54?±?12.35 years, mean BMI 25.9?±?3.44 kg/m²) with diagnoses of idiopathic pulmonary fibrosis (IPF; n?=?17), stage II–III sarcoidosis (n?=?15), or scleroderma (n?=?18). The frequency of OSA was 68 %. The mean apnea–hypopnea index (AHI) was 11.4?±?12.5. OSA was more common in IPF patients (p?=?0.009). The frequency of rapid eye movement-related sleep apnea was 52.9 %. The frequency of OSA was higher in patients with a disease severity index ≥3 (p?=?0.04). The oxygen desaturation index and the AHI were higher in patients with diffuse radiological involvement (p?=?0.007 and p?=?0.043, respectively).

Conclusions

OSA is common in ILD. PSG or at minimum nocturnal oximetry should be performed, particularly in patients with functionally and radiologically severe disease.     

A case–control study of craniofacial features of children with obstructed sleep apnea

Objective

This study aims to analyze differences in the skeletal, dental, and soft tissue components of craniofacial structure predisposing to the pediatric obstructive sleep apnea, by a comparison of the cephalograms between children with obstructive sleep apnea (OSA) and controls.

Materials and methods

The study enrolled a total of 30 children who were composed of the following two groups: 15 OSA patients and 15 controls. The two groups were strictly matched by age and sex. Lateral head radiographs were obtained and then cephalometric measurements were compared between the two. Fifty-six measurements were determined to study various skeletal, soft tissue, and airway structure.

Results

Marked differences were demonstrated in terms of SNB, PG-NB, lower facial height, H-C3Me, and adenoid (A) and tonsil (T/P). The SNB angle (75.82?±?4.30) in case group was smaller than in the control (78.71?±?2.61; p?=?0.035), the PG/NB value in case group (1.32?±?0.84?mm) was higher than that in the control (0.62?±?0.60?mm; p?=?0.015). The anterior lower facial height was 65.12?±?5.91?mm in case group (p?=?0.048), while the anterior lower facial height in control was 61.51?±?3.22?mm. The position of hyoid was lower in case group (5.30?±?3.67?mm) compared with the control one (2.64?±?2.58?mm; p?=?0.029). Furthermore, the patients with OSA had larger As and T/Ps than the controls.

Conclusions

The case group differed from the control group in the length of mandible, anterior lower facial height, position of hyoid and the chin, and the size of the As and T/Ps.     

CPAP therapy in patients with idiopathic pulmonary fibrosis and obstructive sleep apnea: does it offer a better quality of life and sleep?

Background

The recent literature shows an increased incidence of obstructive sleep apnea (OSA) in patients with idiopathic pulmonary fibrosis (IPF). On the other hand, there are no published studies related to continuous positive airway pressure (CPAP) treatment in this patient group. Our aim was to assess the effect of CPAP on sleep and overall life quality parameters in IPF patients with OSA and to recognize and overcome possible difficulties in CPAP initiation and acceptance by these patients.

Methods

Twelve patients (ten males and two females, age 67.1?±?7.2 years) with newly diagnosed IPF and moderate to severe OSA, confirmed by overnight attended polysomnography, were included. Therapy with CPAP was initiated after a formal in-lab CPAP titration study. The patients completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), the Functional Outcomes in Sleep Questionnaire (FOSQ), the Fatigue Severity Scale (FSS), the SF-36 quality of life questionnaire, and the Beck Depression Inventory (BDI) at CPAP initiation and after 1, 3, and 6 months of effective CPAP therapy.

Results

A statistically significant improvement was observed in the FOSQ at 1, 3, and 6 months after CPAP initiation (baseline 12.9?±?2.9 vs. 14.7?±?2.6 vs. 15.8?±?2.1 vs. 16.9?±?1.9, respectively, p?=?0.02). Improvement, although not statistically significant, was noted in ESS score (9.2?±?5.6 vs. 7.6?±?4.9 vs. 7.5?±?5.3 vs. 7.7?±?5.2, p?=?0.84), PSQI (10.7?±?4.4 vs. 10.1?±?4.3 vs. 9.4?±?4.7 vs. 8.6?±?5.2, p?=?0.66), FSS (39.5?±?10.2 vs. 34.8?±?8.5 vs. 33.6?±?10.7 vs. 33.4?±?10.9, p?=?0.44), SF-36 (63.2?±?13.9 vs. 68.9?±?13.5 vs. 72.1?±?12.9 vs. 74.4?±?11.3, p?=?0.27), and BDI (12.9?±?5.5 vs. 10.7?±?4.3 vs. 9.4?±?4.8 vs. 9.6?±?4.5, p?=?0.40). Two patients had difficulty complying with CPAP for a variety of reasons (nocturnal cough, claustrophobia, insomnia) and stopped CPAP use after the first month, despite intense follow-up by the CPAP clinic staff. Heated humidification was added for all patients in order to improve the common complaint of disabling nocturnal cough.

Conclusion

Effective CPAP treatment in IPF patients with OSA results in a significant improvement in daily living activities based on the FOSQ, namely an OSA-specific follow-up instrument. Improvement was also noted in other questionnaires assessing quality of life, though not to a statistically significant degree, probably because of the multifactorial influences of IPF on physical and mental health. The probability of poor CPAP compliance was high and could only be eliminated with intense follow-up by the CPAP clinic staff.     

Cardiopulmonary coupling analysis: changes before and after treatment with a mandibular advancement device

Purpose

The aim of this study is to evaluate the changes of sleep quality in patients using a mandibular advancement device (MAD) for obstructive sleep apnea (OSA) based upon cardiopulmonary coupling (CPC).

Methods

A total of 52 patients (mean age 53.7?±?9.6 years, range 33–74 years) were included in this study. Of them, there were 47 males (90.4 %). All subjects were diagnosed with OSA after in-laboratory full-night polysomnography and reevaluated after 3-month use of a MAD. At baseline, apnea-hypopnea index (AHI) was 33.6?±?17.0, Epworth sleepiness scale was 10.5?±?4.8, and Pittsburgh sleep quality index was 5.8?±?2.8. The CPC parameters were extracted from single-lead electrocardiography of polysomnography. We compared CPC parameters at baseline with those after 3-month use of a MAD.

Results

All respiratory indices improved with the use of MAD. However, there were no differences in the sleep architectures except N3 sleep (3.7?±?4.3 to 6.9?±?6.4 %, p?p?p?p?=?0.004) and very low frequency coupling (11.7?±?7.2 to 15.3?±?6.6 %, p?=?0.028) significantly increased. The change of AHI significantly correlated with changes of the CPC parameters: negatively correlated with high-frequency coupling change (r?=??0.572, p?r?=?0.604 and 0.497, respectively; p?Epworth sleepiness scale and Pittsburgh sleep quality index after MAD therapy showed no significant correlation with the changes in the CPC parameters.

Conclusions

To our knowledge, this is the first study to evaluate the quality of sleep in patients using a MAD for their OSA based upon CPC analysis. Low-frequency coupling decreased as AHI improved, while high-frequency coupling increased as AHI improved. The CPC parameters showed that the sleep quality was improved by MAD therapy.     

An electrocardiogram-based analysis evaluating sleep quality in patients with obstructive sleep apnea

Objective

The study compares polysomnography (PSG) and cardiopulmonary coupling (CPC) sleep quality variables in patients with (1) obstructive sleep apnea (OSA) and (2) successful and unsuccessful continuous positive airway pressure (CPAP) response.

Patients/methods

PSGs from 50 subjects (32 F/18 M; mean age 48.4?±?12.29 years; BMI 34.28?±?9.33) were evaluated. OSA patients were grouped by no (n?=?16), mild (n?=?13), and moderate to severe (n?=?20) OSA (apnea–hypopnea index (AHI)?≤?5, >5–15, >15 events/h, respectively). Outcome sleep quality variables were sleep stages in non-rapid eye movement, rapid eye movement sleep, and high (HFC), low (LFC), very low-frequency coupling (VLFC), and elevated LFC broad band (e-LFC_BB). An AHI?≤?5 events/h and HFC?≥?50 % indicated a successful CPAP response. CPC analysis extracts heart rate variability and QRS amplitude change that corresponds to respiration. CPC-generated spectrograms represent sleep dynamics from calculated coherence product and cross-power of both time series datasets.

Results

T tests differentiated no and moderate to severe OSA groups by REM % (p?=?0.003), HFC (p?=?0.007), VLFC (p?=?0.007), and LFC/HFC ratio (p?=?0.038) variables. The successful CPAP therapy group (n?=?16) had more HFC (p?=?0.003), less LFC (p?=?0.003), and e-LFC_BB (p?=?0.029) compared to the unsuccessful CPAP therapy group (n?=?8). PSG sleep quality measures, except the higher arousal index (p?=?0.038) in the unsuccessful CPAP group, did not differ between the successful and unsuccessful CPAP groups. HFC?≥?50 % showed high sensitivity (77.8 %) and specificity (88.9 %) in identifying successful CPAP therapy.

Conclusions

PSG and CPC measures differentiated no from moderate to severe OSA groups and HFC?≥?50 % discriminated successful from unsuccessful CPAP therapy. The HFC?≥?50 % cutoff showed clinical value in identifying sleep quality disturbance among CPAP users.     

Glucocorticoid treatment impairs microvascular function in healthy men in association with its adverse effects on glucose metabolism and blood pressure: a randomised controlled trial

Aims/hypothesis

Glucocorticoids (GCs) are widely used anti-inflammatory agents that frequently induce side effects, including insulin resistance, diabetes and hypertension. Here, we investigated the contribution of microvascular dysfunction to the development of these adverse effects in healthy men.

Methods

In a randomised, placebo-controlled, dose–response intervention study, 32 healthy normoglycaemic men (age: 21?±?2 years; BMI: 21.9?±?1.7 kg/m²) were allocated to receive prednisolone 30 mg once daily (n?=?12), prednisolone 7.5 mg once daily (n?=?12) or placebo (n?=?8) for 2 weeks using block randomisation. A central office performed the treatment allocation, and medication was dispersed by the hospital pharmacy that was also blinded. Treatment allocation was kept in concealed envelopes. Participants, study personnel conducting the measures and assessing the outcome were blinded to group assignment. The study was conducted at a university hospital. Primary endpoint was prednisolone-induced changes in microvascular function, which was assessed by capillary microscopy. Insulin sensitivity was determined by hyperinsulinaemic–euglycaemic clamp and postprandial glycaemic excursions by standardised meal tests.

Results

Compared with placebo, prednisolone 7.5 mg and 30 mg decreased insulin-stimulated capillary recruitment by 9?±?4% and 17?±?3%, respectively (p?<?0.01). In addition, prednisolone 7.5 mg and 30 mg reduced insulin sensitivity (M value) by ?11.4?±?4.5 μmol kg^?1 min^?1 and ?25.1?±?4.1 μmol kg^?1 min^?1 (p?<?0.001) and increased postprandial glucose levels by 11?±?5% and 27?±?9% (p?<?0.001), respectively. Only high-dose prednisolone increased systolic blood pressure (6?±?1.2 mmHg, p?=?0.006). Prednisolone-induced changes in insulin-stimulated capillary recruitment were associated with insulin sensitivity (r?=?+0.76; p?<?0.001), postprandial glucose concentrations (r?=??0.52; p?<?0.03) and systolic blood pressure (r?=??0.62; p?<?0.001). Prednisolone increased resistin concentrations, which were negatively related to insulin-stimulated capillary recruitment (r?=??0.40; p?=?0.03). No effects were noted on adiponectin and leptin concentrations. Prednisolone treatment was well tolerated; none of the participants left the study.

Conclusions/interpretation

Prednisolone-induced impairment of insulin-stimulated capillary recruitment was paralleled by insulin resistance, increased postprandial glucose levels, hypertension and increased circulating resistin concentrations in healthy men. We propose that GC-induced impairments of microvascular function may contribute to the adverse effects of GC treatment on glucose metabolism and blood pressure.

Trial registration

isrctn.org ISRTCN 78149983

Funding

The study was funded by the Dutch Top Institute Pharma T1-106.     

Effects of twin block appliance on obstructive sleep apnea in children: a preliminary study

Background

Oral appliances are increasingly advocated as a treatment option for obstructive sleep apnea (OSA). However, it is not clear how the different designs influence treatment efficacy in children. The aim of this study was to investigate the effects of twin block (TB) appliance on children with OSA and mandibular retrognathia.

Methods

A total of 46 children (31 males, 15 females, aged 9.7?±?1.5 years, BMI: 18.1?±?1.04 kg/m²) diagnosed with mandibular retrognathia and OSA by polysomnography (PSG) and with no obesity or adenotonsillar hypertrophy were recruited for the study. Patients in the treatment group were instructed to wear the twin block oral appliance full time for an average of 10.8 months. The efficacy of treatment was determined by monitoring the PSG and cephalometric changes before and after appliance removal. Data were analyzed using paired t test.

Results

Results showed an improvement in patient's facial profile after treatment with the TB appliance. The average AHI index decreased from 14.08?±?4.25 to 3.39?±?1.86 (p?<?0.01), and the lowest SaO₂ increased from 77.78?±?3.38 to 93.63?±?2.66 (p?<?0.01). Cephalometric measurements showed a significant increase in the superior posterior airway space, middle airway space, SNB angle and facial convexity which indicate an enhancement in mandibular growth, and reduction in the soft palate length.

Conclusions

This preliminary study suggests that twin block appliance may improve the patient's facial profile and OSA symptoms in a group of carefully selected children presented with both OSA and mandibular retrognathia symptoms.     

Lack of Effect of Nitrates on Exercise Stress Test Results in Patients with Microvascular Angina

Purpose

To assess the effects of short-acting nitrates on exercise stress test (EST) results and the relation between EST results and coronary blood flow (CBF) response to nitrates in patients with microvascular angina (MVA).

Methods

We completed 2 symptom/sign limited ESTs on 2 separate days, in a random sequence and in pharmacological washout, in 29 MVA patients and in 24 patients with obstructive coronary artery disease (CAD): one EST was performed without any intervention (control EST, C-EST), and the other after sublingual isosorbide dinitrate, 5 mg (nitrate EST, N-EST). CBF response to nitroglycerin (25 μg) was assessed in the left anterior descending coronary artery by transthoracic Doppler-echocardiography.

Results

At C-EST. ST-segment depression ≥1 mm (STD) was induced in 26 (90 %) and 23 (96 %) MVA and CAD patients, respectively (p?=?0.42), whereas at N-EST, STD was induced in 25 (86 %) and 14 (56 %) MVA and CAD patients, respectively (p?=?0.01). Time and rate pressure product at 1 mm STD increased during N-EST, compared to C-EST, in CAD patients (475?±?115 vs. 365?±?146 s, p?<?0.001; and 23511?±?4352 vs. 20583?±?6234 bpm?mmHg, respectively, p?=?0.01), but not in MVA patients (308?±?160 vs. 284?±?136 s; p?=?0.19; and 21290?±?5438 vs. 20818?±?4286 bpm?mmHg, respectively, p?=?0.35). In MVA patients, a significant correlation was found between heart rate at STD during N-EST and CBF response to nitroglycerin (r?=?0.40, p?=?0.04).

Conclusions

Short-acting nitrates improve EST results in CAD, but not in MVA patients. In MVA patients a lower nitrate-dependent coronary microvascular dilation may contribute to the lack of effects of nitrates on EST results.     

Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity

Aims/hypothesis

Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity.

Methods

Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined.

Results

Maternal insulin increased from a fasting level of 67?±?25 pmol/l (mean ± SD) to 918?±?492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4?±?0.3 to 7.4?±?1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297?±?99 to 235?±?84 ms (p?=?0.01) and then remained stable until 120 min (235?±?84 vs 251?±?91 ms, p?=?0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r?=?0.68, p?=?0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283?±?79 ms) than those of insulin-sensitive mothers (178?±?46 ms, p?=?0.03).

Conclusions/interpretation

Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.