Piotr Bielicki

Diabetes Mellitus Prevalence and Control in Sleep-Disordered Breathing: The European Sleep Apnea Cohort (ESADA) Study

BACKGROUND OSA is associated with an increased risk of cardiovascular morbidity. A driver of this is metabolic dysfunction and in particular type 2 diabetes mellitus (T2DM). Prior studies identifying a link between OSA and T2DM have excluded subjects with undiagnosed T2DM, and there is a lack of population-level data on the interaction between OSA and glycemic control among patients with diabetes. We assessed the relationship between OSA severity and T2DM prevalence and control in a large multinational population. METHODS We performed a cross-sectional analysis of 6,616 participants in the European Sleep Apnea Cohort (ESADA) study, using multivariate regression analysis to assess T2DM prevalence according to OSA severity, as measured by the oxyhemoglobin desaturation index. Patients with diabetes were identified by previous history and medication prescription, and by screening for undiagnosed diabetes with glycosylated hemoglobin (HbA1c) measurement. The relationship of OSA severity with glycemic control was assessed in diabetic subjects. RESULTS T2DM prevalence increased with OSA severity, from 6.6% in subjects without OSA to 28.9% in those with severe OSA. Despite adjustment for obesity and other confounding factors, in comparison with subjects free of OSA, patients with mild, moderate, or severe disease had an OR (95% CI) of 1.33 (1.04-1.72), 1.73 (1.33-2.25), and 1.87 (1.45-2.42) (P < .001), respectively, for prevalent T2DM. Diabetic subjects with more severe OSA had worse glycemic control, with adjusted mean HbA1c levels 0.72% higher in patients with severe OSA than in those without sleep-disordered breathing (analysis of covariance, P < .001). CONCLUSIONS Increasing OSA severity is associated with increased likelihood of concomitant T2DM and worse diabetic control in patients with T2DM.

Premature ventricular complex-induced chronic cough and cough syncope

The present case study reports a case of chronic cough and cough syncope associated with frequent premature ventricular complexes (PVCs). Careful analysis of cough-related symptoms and ECG monitoring led to the suspicion of PVC-induced cough. A coincidence between PVCs and episodes of cough was also documented by a portable multichannel recorder. Moreover, Doppler echocardiography revealed a PVC-induced transient increase in the pulmonary artery blood flow. After exclusion of other possible aetiologies, complete relief of chronic cough and cough syncope was achieved by radiofrequency ablation of the arrhythmogenic focus located in the right ventricular outflow tract. Premature ventricular complexes should be considered as a cause of chronic cough and cough syncope and an interdisciplinary cooperation can lead to successful diagnosis and treatment of this condition.

Diagnosis and Management of Premature Ventricular Complexes-Associated Chronic Cough

BACKGROUND Chronic cough frequently remains unexplained. Although various cardiac arrhythmias have already been reported as a cause of chronic cough, this phenomenon has not been evaluated prospectively. Therefore, we studied the incidence and management of cough associated with premature ventricular complexes (PVCs) in a population of patients with this condition. METHODS Patients without organic heart disease who had been referred for the management of symptomatic PVC were evaluated prospectively. PVC-associated cough was recognized if cough episodes occurred just after spontaneous or induced PVC or observed in an ECG or a multichannel recording system that included ECG. A differential diagnosis of cough was performed according to the guidelines on cough. Afterward, antiarrhythmic therapy was instituted to eliminate PVC and cough. RESULTS Of the 120 patients who were referred for the management of PVC, 10 had a chronic cough. After extensive workup for the cause of chronic cough, the cough was thought to be solely due to PVC in one patient, partially due to PVC plus another cause in five patients, and not due to PVC but to nonasthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and chronic sinusitis in four patients. Patients with PVC-associated cough reported more severe perception of symptoms associated with arrhythmia than patients without cough (mean [+/- SD] visual analog scale score, 8.2 +/- 0.5 vs 5.7 +/- 1.6, respectively; p < 0.01). PVC-associated cough disappeared after antiarrhythmic treatment (radiofrequency ablation [n = 4], oral antiarrhythmic agent [n = 1]), or after spontaneous remission of PVC (n = 1). CONCLUSIONS PVC may be a cause of chronic cough. Interdisciplinary cooperation is warranted for the proper diagnosis and management of PVC-associated cough.

Obstructive sleep apnea in shift workers.

OBJECTIVE In modern society, the number of people working night shifts is increasing. The aim of the study was to investigate effects of shift work on obstructive sleep apnea syndrome (OSAS) and oxygen desaturation index (ODI) during daytime and nighttime sleep in patients with OSAS. METHODS Twenty-nine male and two female shift workers (SW) with OSAS were investigated. Their mean age was 47±10years, BMI 32±4kg/m(2). The control group consisted of 10 male patients with OSAS, matched for age, BMI, and hours of night sleep, not working on shifts. Nocturnal and diurnal after night shift or sleep deprivation polysomnographies (PSG) were performed in all subjects. RESULTS Comparison of diurnal and nocturnal PSG recordings in the SW group demonstrated a significantly higher AHI in diurnal PSG after the night shift vs. nocturnal PSG (50±27 vs. 32±22, P<0.05). During daytime sleep SW OSAS patients demonstrated higher AHI than sleep-deprived controls (49.7±26.6 vs. 30.1±21.9, P<0.05) and higher ODI (44.1±25.1 vs. 21.6±18.5, P<0.05). CONCLUSIONS Significantly higher severity of OSAS during daytime sleep after night shift may intensify unfavorable health effects of OSAS. Patients with OSAS if not effectively treated should avoid nighttime work.

T, B, and NKT Cells in Systemic Inflammation in Obstructive Sleep Apnoea

Background. Obstructive sleep apnoea syndrome (OSAS) brings risk of serious complications. The study objective was to assess elements of the cellular immune response in the course of OSAS. Methods. Peripheral blood (PB) lymphocytes: T, B, NK, NKT-like, Th, Tc, and HLA DR+ T cells were evaluated by flow cytometry of 48 OSA patients; the concentration of adiponectin, interleukin 1β, and TNFα was measured by ELISA method. The OSA complication score was developed and used for statistical analysis. Results. The proportion of B cells and Th/Tc ratio were significantly lower in the BP of OSA patients when compared with control subjects (median 7.9 versus 10.9%, 0.9 versus 1.5, p < 0.05). The proportion of Tc, NK, NKT-like, and HLADR positive T cells were elevated in OSA patients when compared with healthy subjects (36.4 versus 26.8, 15.5 versus 8.5, 5.7 versus 3.0, and 8.4 versus 4.5%, p < 0.05, resp.) and were more pronounced in patients with metabolic syndrome. The grade of OSA complication score correlated with systemic inflammation markers and the proportion of B cells. The value of adiponectin/BMI ratio correlated significantly with SpO2 (r = 0.31, p < 0.05), CRP (r = −0.35, p < 0.05), TNFα concentration (r = −0.36, p < 0.05), and proportion of B cells (r = 0.32, p < 0.05). Conclusion. Lymphocytes B, Tc, NK, NKT-like, and adiponectin are involved in systemic immune response in OSA patients possibly predisposing them to cardiovascular and metabolic complications.

Cytokine gene polymorphisms in obstructive sleep apnoea/hypopnoea syndrome

OBJECTIVE The pro-inflammatory cytokines, TNF-α, IL-6, and IL-8 are elevated in obstructive sleep apnoea/hypopnoea syndrome (OSAHS). Cytokine gene interactions are complex and haplotype analysis may be more informative. We hypothesized that the effects of TNF-α in OSAHS might be due to linkage disequilibrium of the TNF-α (-308A) single nucleotide polymorphism (SNP) with other polymorphisms within the TNF-α gene, and that predisposition to elevated IL-6 and IL-8 levels in OSAHS might be attributable to pro-inflammatory IL-6 and IL-8 gene promoter polymorphisms. METHOD 173 subjects were classified as having definite OSAHS or not on the basis of apnoea-hypopnoea frequency, sex, age, and symptoms. Population controls comprised 192 random UK blood donors. Genotyping was undertaken for the TNF-α promoter polymorphisms (-1031, -863, -857, -238), two lymphotoxin-α polymorphisms (intron 1 and Thr60Asn), the pro-inflammatory IL-6 gene promoter polymorphism (-174), and IL-8 gene promoter polymorphisms (-251; -781). RESULTS There was no significant difference between groups re: genotype/allelic frequency in the genes investigated. Association between disease status and the TNF-α alleles independently (TNF-103, TNF-803, TNF-857, TNF-238) with five haplotypes of TNF-α was not significant (p > 0.05). There was no difference in allelic or genotypic frequencies between obese and non-obese subjects with OSAHS. The TNF-α (-863A) allele alone, was significantly associated with obesity (OR 2.4; CI95% 1.1-5; p = 0.025). CONCLUSION Only the TNF-α (308A) SNP appears to be significantly associated with OSAHS. The impact of cytokine gene polymorphisms on phenotypic expression of inflammation in OSAHS is likely to be complex.

Continuous Positive Airway Pressure Treatment Increases Bronchial Reactivity in Obstructive Sleep Apnea Patients

Background: The effects of continuous positive airway pressure (CPAP) treatment on the function of the lower airways are poorly understood. One of the methods used to determine the influence of positive pressure breathing on lower airways is the bronchial hyperreactivity test. Some authors report that CPAP increases bronchial hyperreactivity, while others report decreases. Objectives: To assess the influence of CPAP treatment on bronchial reactivity and the effects of bronchial hyperreactivity on compliance to CPAP treatment. Methods: The study group consisted of 101 obstructive sleep apnea syndrome patients (88 men and 13 women) with a mean age of 51 ± 11 years, mean apnea-hypopnea index of 53 ± 20 and mean body mass index of 32.6 ± 5.4. Patients were randomly assigned to a treatment group that received 3 weeks of CPAP therapy (group 1) or to a nontreatment control group (group 2). Pulmonary function tests and the methacholine bronchial provocation test were performed at baseline and 3 weeks later. Results: There were no statistically significant differences between treated and control groups in anthropometry and polysomnography variables. At baseline, bronchial hyperreactivity was found in 6 patients from group 1 and 5 patients from group 2. A significant increase in bronchial reactivity was observed after CPAP treatment. Log PC20M decreased from 1.38 ± 0.30 at baseline to 1.26 ± 0.50 (p < 0.05). In group 2, changes were statistically insignificant. Patients with bronchial hyperreactivity during CPAP treatment were characterized by significantly lower FEV1, FVC and MEF50 values. Conclusions: CPAP produces statistically significant bronchial hyperreactivity. However, there were no clinical symptoms and it is not necessary to withdraw previous therapies.

Thyroid Hormone Levels and TSH Activity in Patients with Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSAS) is characterized by complete cessation of inspiratory flow (apnea) or upper airway airflow limitation (hypopnea) with increased respiratory muscle activity, which is repeatedly observed during sleep. Hypothyroidism has been described as a rare cause of OSAS, but it is considered to be the main cause of breathing disorders during sleep in patients in whom an improvement of OSAS is observed after thyroid hormone replacement therapy. Nevertheless, euthyreosis due to thyroxine replacement in patients with OSAS often does not improve the breathing disorder and treatment with continuous positive airway pressure is usually applied. The aim of this study was to assess thyroid function in patients with OSAS. We studied 813 patients in whom severe OSAS was diagnosed; the mean apnea-hypopnea index was 44.0. Most of the patients were obese (mean BMI 33.1 ± 6.6 kg/m2) and had excessive daytime sleepiness (ESS 12.8 ± 6.6). With the thyroid stimulating hormone (TSH) concentration as the major criterion, hypothyroidism was diagnosed in 38 (4.7%) and hyperthyroidism was diagnosed in 31 (3.8%) patients. Analysis of basic anthropometric data, selected polysomnography results, and TSH, fT3, and fT4 values did not reveal any significant correlations. In conclusion, the incidence of thyroid function disorders seems to be no different in OSAS than that in the general population. We did not find correlations between TSH activity and the severity of breathing disorders during sleep.

Fixed But Not Autoadjusting Positive Airway Pressure Attenuates the Time-dependent Decline in Glomerular Filtration Rate in Patients With OSA

Background The impact of treating OSA on renal function decline is controversial. Previous studies usually included small samples and did not consider specific effects of different CPAP modalities. The aim of this study was to evaluate the respective influence of fixed and autoadjusting CPAP modes on estimated glomerular filtration rate (eGFR) in a large sample of patients derived from the prospective European Sleep Apnea Database cohort. Methods In patients of the European Sleep Apnea Database, eGFR prior to and after follow‐up was calculated by using the Chronic Kidney Disease‐Epidemiology Collaboration equation. Three study groups were investigated: untreated patients (n = 144), patients receiving fixed CPAP (fCPAP) (n = 1,178), and patients on autoadjusting CPAP (APAP) (n = 485). Results In the whole sample, eGFR decreased over time. The rate of eGFR decline was significantly higher in the subgroup with eGFR above median (91.42 mL/min/1.73 m2) at baseline (P < .0001 for effect of baseline eGFR). This decline was attenuated or absent (P < .0001 for effect of treatment) in the subgroup of patients with OSA treated by using fCPAP. A follow‐up duration exceeding the median (541 days) was associated with eGFR decline in the untreated and APAP groups but not in the fCPAP group (P < .0001 by two‐way ANOVA for interaction between treatment and follow‐up length). In multiple regression analysis, eGFR decline was accentuated by advanced age, female sex, cardiac failure, higher baseline eGFR, and longer follow‐up duration, whereas there was a protective effect of fCPAP. Conclusions fCPAP but not APAP may prevent eGFR decline in OSA.

Treatment with continuous positive airway pressure and diurnal and nocturnal serum melatonin concentration in patients with obstructive sleep apnea

INTRODUCTION Melatonin secretion, one of the main factors controlling the sleep-wake rhythm, may be disrupted in patients with sleep disorders. OBJECTIVES The aim of the study was to evaluate the profile of circadian melatonin secretion in patients with obstructive sleep apnea (OSA) and to assess the impact of 2-day and 3-month treatment with continuous airway pressure (CPAP) on diurnal and nocturnal serum melatonin levels. PATIENTS AND METHODS Serum melatonin levels were evaluated in 71 untreated patients with OSA and 18 healthy controls at 6 time points: 10 AM, 2 PM, 6 PM, 10 PM, 2 AM, and 6 AM. The measurements were repeated after 2 days and 3 months of CPAP treatment. RESULTS Melatonin secretion rhythm was altered in 25.4% of the patients with OSA. In patients with preserved secretion rhythm, the serum melatonin level was significantly lower at 2 AM and 6 AM, compared with healthy controls: 68.2 pg/ml (interquartile range [IQR], 30.1-109.8 pg/ml) vs 109.1 pg/ml (IQR, 63-167.9 pg/ml), P = 0.02 and 40.8 pg/ml (IQR, 20.8-73.2 pg/ml) vs 67.7 pg/ml (IQR, 32.7-131.7 pg/ml), P = 0.04, respectively. Melatonin levels did not change significantly after the 2-day and 3-month CPAP treatment. However, at 3 months, a shift of the peak melatonin concentration to 2 AM was observed in patients with an altered secretion rhythm. CONCLUSIONS OSA has a significant effect on serum melatonin levels. Neither short-term nor long-term CPAP treatment significantly changes melatonin concentrations; however, our results seem to indicate that a 3-month CPAP treatment may be helpful in restoring the physiological rhythm of melatonin secretion in patients with OSA.