Role of primary care in the follow-up of patients with obstructive sleep apnoea undergoing CPAP treatment: a randomised controlled trial.

OBJECTIVE: To evaluate whether follow-up of patients with obstructive sleep apnoea (OSA) undergoing CPAP treatment could be performed in primary care (PC) settings. DESIGN: Non-inferiority, randomised, prospective controlled study. SETTINGS: Sleep unit (SU) at the University Hospital and in 8 PC units in Lleida, Spain. PARTICIPANTS: Patients with OSA were randomised to be followed up at the SU or PC units over a 6-month period. MAIN OUTCOMES MEASURED: The primary outcome was CPAP compliance at 6 months. The secondary outcomes were Epworth Sleep Scale (ESS) score, EuroQoL, patient satisfaction, body mass index (BMI), blood pressure and cost-effectiveness. RESULTS: We included 101 patients in PC ((mean±SD) apnoea-hypopnoea index (AHI) 50.8±22.9/h, age 56.2±11 years, 74% male) and 109 in the SU (AHI 51.4±24.4/h, age 55.8±11 years, 77% male)). The CPAP compliance was (mean (95% CI) 4.94 (4.47 to 5.5) vs 5.23 (4.79 to 5.66) h, p=0.18) in PC and SU groups, respectively. In the SU group, there were greater improvements in ESS scores (mean change 1.79, 95% CI +0.05 to +3.53, p=0.04) and patient satisfaction (-1.49, 95% CI -2.22 to -0.76); there was a significant mean difference in BMI between the groups (0.57, 95% CI +0.01 to +1.13, p=0.04). In the PC setting, there was a cost saving of 60%, with similar effectiveness, as well as a decrease in systolic blood pressure (-5.32; 95% CI -10.91 to +0.28, p=0.06). CONCLUSIONS: For patients with OSA, treatment provided in a PC setting did not result in worse CPAP compliance compared with a specialist model and was shown to be a cost-effective alternative. TRIAL REGISTRATION NUMBER: Clinical Trials NCT01918449.

The Carotid Body Does Not Mediate the Acute Ventilatory Effects of Leptin.

Leptin is a hormone produced mostly in adipose tissue and playing a key role in the control of feeding and energy expenditure aiming to maintain a balance between food intake and metabolic activity. In recent years, it has been described that leptin might also contributes to control ventilation as the administration of the hormone reverses the hypoxia and hypercapnia commonly encountered in ob/ob mice which show absence of the functional hormone. In addition, it has been shown that the carotid body (CB) of the rat expresses leptin as well as the functional leptin-B receptor. Therefore, the possibility exists that the ventilatory effects of leptin are mediated by the CB chemoreceptors. In the experiments described below we confirm the stimulatory effect of leptin on ventilation, finding additionally that the CB does not mediate the instant to instant control of ventilation.

Impact of treating obesity hypoventilation syndrome on body mass index.

STUDY OBJECTIVES: To evaluate the impact of positive airway pressure (PAP) therapy on body mass index (BMI) in patients with obesity hypoventilation syndrome (OHS) associated with obstructive sleep apnea (OSA). METHODS: A systematic review using the following terms: "obesity hypoventilation syndrome" AND "treatment" AND "randomized" using Cochrane Central Register of Controlled Trials, Medline and Web of Science was performed from the first data available until February 10, 2023. The inclusion criteria were: (1) original article; (2) adult OHS with concomitant OSA (apnea-hypopnea index or AHI ≥5 events/h); (3) randomized trial with PAP arm and standard care (control); (4) BMI evaluation at baseline and after the first months. We performed an individual participant data meta-analysis of randomized controlled trials. RESULTS: Our initial search retrieved 32 articles and 3 randomized studies fulfilled study criteria and were included in the final analysis, leading to a total of 342 participants. Patients were predominantly females (62%) and had OHS associated with at least mild OSA. As compared to baseline, a decrease in BMI was observed at study endpoint but this difference was not different intergroups (-0.50 ± 1.49 and -0.50 ±1.83, in control and PAP groups respectively (p=0.939)). Weight change was not associate with PAP adherence, OSA severity or use of supplemental oxygen. CONCLUSIONS: In contrast to treatment of eucapnic OSA with PAP that is associated with weight gain, treatment of OSA+OHS patients with or without PAP is associated with weight loss. Future studies are necessary to elucidate the mechanism by which weight loss occurs.

Validity of spirometry performed online.

Spirometry is essential for the diagnosis and management of common respiratory diseases. However, its use and quality are low in primary care. An important reason for this is the technical difficulty in performing conventional spirometry. If high-quality spirometry could be performed online, from the pulmonary function laboratory in hospitals, most of the technical problems could be solved. The aim of the present study was to compare spirometries performed online by remote technicians with conventional spirometry. This was a controlled, randomised crossover study of 261 patients referred from primary care centres for pulmonary consultation. They were randomised to undergo either conventional or online spirometry. The technician, located remotely, controlled the spirometer computer. Using a teleconference link, the technician guided the patient through the spirometry. The comparison between conventional and online spirometries was performed on intention to treat and per protocol bases for spirometric values and quality criteria. Agreement between the two spirometric methods was assessed with a Bland-Altman plot. A subpopulation of off-range patients was also characterised. Finally, intra- and interobserver agreement was evaluated using the intraclass correlation coefficient. No clinically significant differences were seen between the online and conventional spirometric values in both the intention to treat and per protocol analyses. The agreement in Bland-Altman analysis was poorer for intention to treat than for the per protocol analysis. The latter had a lower percentage of off-range patients and high agreement to determine abnormal spirometry in the off-range group. Conventional spirometry had a higher percentage of patients with spirometric quality criteria although the quality criteria difference was only 5.9%, when both procedures were the first to start. Very good agreement was found between intra- and interobserver reliability. Spirometry performed online from a hospital can be an adequate alternative to conventional spirometry for primary care centres.

The European Sleep Apnoea Database (ESADA): report from 22 European sleep laboratories.

The European Sleep Apnoea Database (ESADA) reflects a network of 22 sleep disorder centres in Europe enabled by a COST action B26 programme. This ongoing project aims to describe differences in standard clinical care of patients with obstructive sleep apnoea (OSA) and to establish a resource for genetic research in this disorder. Patients with suspected OSA are consecutively included and followed up according to local clinical standards. Anthropometrics, medical history, medication, daytime symptoms and sleep data (polysomnography or cardiorespiratory polygraphy) are recorded in a structured web-based report form. 5,103 patients (1,426 females, mean±sd age 51.8±12.6 yrs, 79.4% with apnoea/hypopnoea index (AHI) ≥5 events·h(-1)) were included from March 15, 2007 to August 1, 2009. Morbid obesity (body mass index ≥35 kg·m(-2)) was present in 21.1% of males and 28.6% of females. Cardiovascular, metabolic and pulmonary comorbidities were frequent (49.1%, 32.9% and 14.2%, respectively). Patients investigated with a polygraphic method had a lower AHI than those undergoing polysomnography (23.2±23.5 versus 29.1±26.3 events·h(-1), p<0.0001). The ESADA is a rapidly growing multicentre patient cohort that enables unique outcome research opportunities and genotyping. The first cross-sectional analysis reveals a high prevalence of cardiovascular and metabolic morbidity in patients investigated for OSA.

Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997-2007.

We aimed to describe changes in the prevalence of chronic obstructive pulmonary disease (COPD) in Spain by means of a repeated cross-sectional design comparing two population-based studies conducted 10 yrs apart. We compared participants from IBERPOC (Estudio epidemiológico de EPOC en España) (n = 4,030), conducted in 1997, with those of EPI-SCAN (Epidemiologic Study of COPD in Spain) (n = 3,802), conducted in 2007. Poorly reversible airflow obstruction compatible with COPD was defined according to the old European Respiratory Society definitions. COPD prevalence in the population between 40 to 69 yrs of age dropped from 9.1% (95% CI 8.1-10.2%) in 1997 to 4.5% (95% CI 2.4-6.6%), a 50.4% decline. The distribution of COPD prevalence by severity also changed from 38.3% mild, 39.7% moderate and 22.0% severe in 1997, to 85.6% mild, 13.0% moderate and 1.4% severe in 2007, and in the 40-69 yr EPI-SCAN sub-sample to 84.3% mild, 15.0% moderate and 0.7% severe. Overall, underdiagnosis was reduced from 78% to 73% (not a significant difference) and undertreatment from 81% to 54% (p<0.05) within this 10-yr frame. The finding of a substantial reduction in the prevalence of COPD in Spain is unexpected, as were the observed changes in the severity distribution, and highlights the difficulties in comparisons between repeated cross-sectional surveys of spirometry in the population.

Apnoeic and obstructive nonapnoeic sleep respiratory events.

Obstructive nonapnoeic event (ONE) scoring is shrouded in confusion. This is important in patients with mild disease, in whom precision is crucial. The aims of the present study were: 1) to identify ONEs using oesophageal pressure (OP) (OP-ONEs) and a noninvasive (NI) method (NI-ONEs); 2) to compare both methods of scoring; and 3) to determine the contribution of ONE definitions to clinical findings. Patients with suspected sleep apnoeas (respiratory disturbance index

Noninvasive positive pressure ventilation and not oxygen may prevent overt ventilatory failure in patients with chest wall diseases.

Some patients with chest wall diseases (CWD) without respiratory failure manifest important alterations in nocturnal gas exchange, as a previous stage to the future development of daytime respiratory failure. The purpose of this study was to evaluate the efficacy of nasal intermittent positive pressure ventilation (NIPPV) during sleep in a group of obese patients and in another group with restrictive thoracic diseases (RTD), comparing the results with those obtained from conventional nocturnal oxygen therapy. From a total of 42 patients with CWD free of daytime respiratory failure, 27 (64%) were considered nocturnal oxygen desaturators without sleep apnea and were included in the study. The study protocol was completed by 21 of these patients. After 2 weeks of treatment, symptoms of dyspnea, morning headaches, and morning obnubilation improved significantly (p<0.05) in both groups of patients after NIPPV but not with oxygen. Baseline daytime PaO2 was 68+/-7 mm Hg in the obese group of patients and 73+/-11 mm Hg in the RTD group. It improved significantly with NIPPV to 73+/-5 mm Hg in obese patients (p<0.05) and to 77+/-12 mm Hg in the RTD group (p<0.05) but did not change with oxygen (68+/-8 mm Hg in the obese group and 73+/-12 mm Hg in the RTD group). Both treatments improved oxygen saturation during sleep, but oxygenation tends to be higher with oxygen than with NIPPV. Only NIPPV was able to normalize the baseline nocturnal alveolar hypoventilation. From the 21 patients treated, 19 decided to continue with long-term NIPPV, one with oxygen, and one refused treatment. We conclude that in patients with CWD who manifest nighttime oxygen desaturation and hypoventilation, early initiation of NIPPV is preferable to supplemental oxygen. Our results also suggest that NIPPV initiated before overt ventilatory failure could prevent its onset.

Geographic variations in prevalence and underdiagnosis of COPD: results of the IBERPOC multicentre epidemiological study.

OBJECTIVES: To ascertain the prevalence, diagnostic level, and treatment of COPD in Spain through a multicenter study comprising seven different geographic areas. DESIGN AND PARTICIPANTS: This is an epidemiologic, multicenter, population-based study conducted in seven areas of Spain. A total of 4,035 men and women (age range, 40 to 69 years) who were randomly selected from a target population of 236,412 subjects participated in the study. INTERVENTIONS: Eligible subjects answered the European Commission for Steel and Coal questionnaire. Spirometry was performed, followed by a bronchodilator test when bronchial obstruction was present. RESULTS: The prevalence of COPD was 9.1% (95% confidence interval [CI], 8.1 to 10.2%), 15% in smokers (95% CI, 12.8 to 17.1%), 12.8% in ex-smokers (95% CI, 10.7 to 14.8%), and 4.1% in nonsmokers (95% CI, 3.3 to 5.1%). The prevalence in men was 14.3% (95% CI, 12.8 to 15. 9%) and 3.9% in women (95% CI, 3.1 to 4.8%). Marked differences were observed between sexes in smoking; the percentage of nonsmokers was 23% in men and 76.3% in women (p<0.0001). The prevalence of COPD varied among the areas, ranging from 4.9% (95% CI, 3.2 to 7.0%) in the area of the lowest prevalence to 18% (95% CI, 14.8 to 21.2%) in the area of the highest. There was no previous diagnosis of COPD in 78.2% of cases (284 of 363). Only 49.3% of patients with severe COPD, 11.8% of patients with moderate COPD, and 10% of patients with mild COPD were receiving some kind of treatment for COPD. Multivariate analysis showed that individuals had a higher probability of having received a previous diagnosis of COPD if they lived in urban areas, were of male gender, were > 60 years old, had higher educational levels, had > 15 pack-year smoking history, or had symptoms of chronic bronchitis. CONCLUSIONS: COPD is a very frequent disease in Spain, and presents significant geographic variations and a very low level of previous diagnosis and treatment, even in the most advanced cases.

The obesity hypoventilation syndrome can be treated with noninvasive mechanical ventilation.

STUDY OBJECTIVES: To assess the effectiveness of nasal noninvasive mechanical ventilation (NIMV) in patients with obesity hypoventilation syndrome (OHS). DESIGN: Clinical assay that compares two groups of patients with hypercapnic respiratory failure, one group with OHS and the other group with kyphoscoliosis, in their basal situation and after 4 months of treatment with nocturnal NIMV. Thirty-six patients (22 patients with OHS and 14 patients with kyphoscoliosis) completed the study protocol. RESULTS: The frequency of symptoms, such as morning headache, morning drowsiness, dyspnea, and leg edema, improved in a statistically significant way in both groups of patients. The sleepiness improved only in the group with OHS. The comparison of frequency of symptoms between both groups of patients after NIMV treatment did not present statistically significant differences. In the resting situation and without nasal ventilation in place, the PO(2) (mean +/- SD) changed from 51 +/- 10 to 64 +/- 11 mm Hg (p < 0.001) and PCO(2) from 58 +/- 10 to 45 +/- 5 mm Hg (p < 0.001) when the patients with OHS were treated with NIMV. In the group of patients with kyphoscoliosis, likewise without nasal ventilation in place, PO(2) changed from 53 +/- 6 to 65 +/- 5 mm Hg (p < 0.001) and PCO(2) from 59 +/- 11 to 45 +/- 4 mm Hg (p < 0.001) with NIMV treatment. When we compared PO(2) and PCO(2) in both groups of patients at the beginning and at the end of NIMV treatment, we did not find statistically significant differences between OHS and kyphoscoliosis. CONCLUSIONS: NIMV improves the clinical symptoms and the respiratory failure of patients with OHS to a similar degree to that reported for diseases in which its use is completely established, such as kyphoscoliosis. Therefore, NIMV could be an alternative to the treatment of patients with OHS.

[Costs of chronic obstructive pulmonary disease in Spain. Estimation from a population-based study]. / Costes de la EPOC en España. Estimación a partir de un estudio epidemiológico poblacional.

OBJECTIVE: In the studies carried out to date, the cost of chronic obstructive pulmonary disease (COPD) may have been overestimated due to the inclusion of previously diagnosed patients seeking medical attention for their symptoms. As a result, the severity of the cases included in these studies may have been greater than in an unselected sample of the general population. The aim of the present study was to estimate the direct cost of COPD on the basis of a representative sample of the overall Spanish population between 40 and 69 years of age (from the IBERPOC study). METHOD: The cost was evaluated retrospectively by means of a questionnaire completed by the 363 patients with COPD from the IBERPOC study with questions referring to the previous year. Standardized spirometry was performed on all the patients by a pneumologist in each of the 7 geographical areas in which the study was carried out. RESULTS: Hospitalization accounted for the greatest expenditure (41% of total), followed by drug therapy (37%). The cost was euro;98.39 per patient, and euro;909.50 per previously diagnosed patient. The cost per person of severe COPD was more than 3 times that of moderate COPD and more than 7 times that of mild COPD. The estimated annual cost of COPD in Spain was euro;238.82 million (for 1997). CONCLUSION: The present study, which was the first to estimate the cost of COPD in a representative sample of the general population, found the cost to be lower than in studies analyzing samples of patients with previous diagnoses of COPD. The cost distribution is not in line with recommended health care practices, underlining the need to optimize resources used to monitor and treat the disease, with an emphasis on early diagnosis.

[Epidemiological study of chronic obstructive pulmonary disease in Spain (IBERPOC): recruitment and field work]. / Estudio epidemiológico de la EPOC en España (IBERPOC): reclutamiento y trabajo de campo.

Chronic obstructive pulmonary disease (COPD) is a large-scale social and health problem. Because prevalence studies have been performed only in certain areas of Spain, the Spanish Society of Pneumology and Chest Surgery initiated the IBERPOC study with the aim of determining the prevalence of COPD in several parts of the country. IBERPOC is a multicenter, population-based epidemiological study in which subjects have been selected randomly. Seven full-time pneumologists work full-time in seven different areas of Spain. A study of this nature involves a series of difficulties that should be taken into account at the time of planning studies of a similar nature. After 5,827 attempts to reach subjects, a total of 4,967 useful contacts were made, to provide 97.3% of the 5,104 contacts expected. Of those 4,967 useful contacts, 4,035 subjects completed interviews. Among the 932 refusals, 882 (94.6%) agreed to answer a short telephone questionnaire. The field work took 13 months to complete, 30% more time than had been anticipated. The rates at which subjects could not be traced differed from one zone to another, ranging between 5% and 30%; higher rates were attributable to the absence of telephone data in the corresponding census report. In one zone, the dispersion of the census population over a very large area supposed greater difficulty and delay in carrying out the study. In conclusion, the rate of participation and the time required for recruitment can be considered satisfactory. The performance of field work by trained, full-time pneumologists has been essential to the development and quality of the study. Similar epidemiological studies should consider problems derived from the lack of adequate census data, as well as to avoid defining areas of extreme population dispersion in order to facilitate field work.

[Epidemiological study of chronic obstructive pulmonary disease in Spain (IBERPOC): prevalence of chronic respiratory symptoms and airflow limitation]. / Estudio IBERPOC en España: prevalencia de síntomas respiratorios habituales y de limitación crónica al flujo aéreo.

The prevalence of chronic respiratory symptoms and chronic airflow limitation (CAFL) was determined in a multicentric epidemiological study carried out in seven different areas of Spain. Based on a target population of 236,412 persons, a random census sample of 4,035 individuals between 40 and 69 years of age was chosen. Subjects answered several questionnaires and performed spirometric tests followed by a bronchodilation test if bronchial obstruction was detected. Respiratory symptoms were reported by 48% of the population (95% CI: 46.4-49.5%) with greater frequency of symptoms among men than women (55.2% versus 41%, p < 0.001). The following levels of prevalence of chronic symptoms were found: cough, 13.5% (95% CI: 12.5-14.6%); expectoration, 10.7% (95% CI: 9.7-11.6%); dyspnea after one flight of stairs, 10.4% (95% CI: 9.5-11.4%); and wheezing, 40.2% (95% CI: 38.7-41.7%). The prevalence of chronic bronchitis (CB) was 4.8% (95% CI: 4.1-5.4%) and was more frequent among men than among women (8.3% and 1.4%, respectively; p < 0.001). Asthma had been diagnosed previously in 4.9% (95% CI: 4.2-5.5%), more often in women than in men (5.8% and 3.8%, respectively; p < 0.003). CAFL was found in 10.6% (95% CI: 9.6-11.5%), 15.8% in men and 5.5% in women (p < 0.001). All respiratory symptoms except asthma were more frequent among smokers than among ex-smokers, and in turn were more common among ex-smokers than non-smokers. The frequency of symptoms increased in accordance with accumulated smoking. The prevalence of CB and CAFL was vastly different from one region to another. Multivariate analysis showed that factors associated independently with the appearance of CB were smoking, age over 60 years, male sex and having worked in industry. In conclusion, respiratory symptoms, including CB and CAFL, are common in the Spanish population. Smoking and amount of smoking are directly related to the frequency of such symptoms. Substantial differences were found in the prevalence of CB and CAFL among the regions where the study was performed.

[Usefulness of transbronchial punction and mediastinoscopy in mediastinal nodal staging of non-microcytic bronchogenic carcinoma. Preliminary study]. / Utilidad de la punción transbronquial y la mediastinoscopia en la estadificación ganglionar mediastínica del carcinoma broncogénico no microcítico. Estudio preliminar.

Preliminary study to compare the sensitivity and specificity of transbronchial needle aspiration (TBNA) and mediastinoscopy/anterior mediastinotomy (MED/AMED) and/or thoracotomy for staging of mediastinal nodes in non-small cell carcinoma. To determine the sensitivity and specificity of computerized tomography (CT) as a screening technique. Thirty-three patients with non-small cell carcinoma but no remote metastasis and good lung function were evaluated. A chest CT scan was performed before bronchoscopy in 27 patients and before surgery in the others. Nodular areas considered diseased based on CT images were staged by TBNA. When CT images were not available before bronchoscopy. TBNA for staging was performed in the subcarinal region. Results by TBNA were compared with those obtained by MED/AMED and/or thoracotomy. The prevalence of metastatic nodular disease was 47%. CT detected enlarged mediastinal nodes in 24 patients; the images were considered normal in 9 patients. Sensitivity and specificity of CT was 93% and 54%, respectively, with a positive predictive value (PPV) of 68% and negative predictive value (NPV) of 87.5%. The sensitivity and specificity of MED/AMED were 73% and 100%, respectively; PPV was 100% and NPV was 75%. The sensitivity and specificity of TBNA were 36% and 92%, respectively; PPV was 83% and NPV was 57%. The pneumothorax with pleural empyema suffered by one patient after MED could have been avoided, given that the earlier TBNA was positive. TBNA is a safe, useful technique for staging nodes in non-small cell carcinoma. Although the sensitivity of TBNA is lower than that of MED, regions that are difficult to reach with the latter technique can be sampled by TBNA. Furthermore, MED can be rendered unnecessary by positive TBNA results. CT imaging of the chest is sensitive but its specificity is low for detecting ganglial metastasis.

[Respiratory symptoms and diagnosis of COPD in smokers of various types to tobacco. Results from the IBERPOC study]. / Síntomas respiratorios y diagnóstico de EPOC en fumadores de distintas labores de tabaco. Resultados del estudio IBERPOC.

BACKGROUND: The aim of this study was to investigate the sociodemographic characteristics, smoking habits, the prevalence of respiratory symptoms and chronic obstructive pulmonary disease (COPD) in four groups of smokers: of cigarettes (SCt), of cigars (SCigar), of both (SB), of cigars currently but of cigarettes in the past (SCigarExCt) and of cigarettes currently but of cigars in the past (SCtExCigar). METHOD: A multicenter epidemiological study enrolling 4,035 subjects aged between 40 and 69 years. One thousand nine hundred sixty-three were non-smokers and 1,146 were current smokers. Among the smokers, 869 were SCt, 37 were SCigar, 97 were SB, 86 were SCigarExCt and 57 were SCtExCigar. We analyzed sociodemographic characteristics, smoking and the prevalence of respiratory symptoms and COPD. RESULTS: Cigar smokers were usually men, of lower socioeconomic status (p < 0.001) and older than cigarette smokers (p < 0.001), but CO concentrations in expired air were lower in the SCigar group than in the SCt group (5 ppm vs 15.7; p < 0.001). Informants who believed their smoking was not detrimental to their health or to that of second-hand smokers made up 86.5% of the SCigar group and 79.1% of the SCigarExCt group. COPD was diagnosed in 13.2% of the SCt group, in 24.7% of the SB group, and in 12.8% of the SCigarExCt group, in comparison with 4% of the non-smokers (p < 0.001 for all comparisons). CONCLUSIONS: SCigar are mainly older men with lower educational levels. Their concentrations of CO in expired air are low and they have little awareness of the health risks posed by their habit. SCigar who were once smokers of cigarettes have a higher prevalence of respiratory symptoms and COPD than non-smokers and the same prevalence of COPD as SCt.

Plasma levels of neuropeptides and metabolic hormones, and sleepiness in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is related to obesity and metabolic disorders. The main clinical symptoms are excessive daytime sleepiness (EDS) and snoring. However, not all patients with OSA manifest EDS. Hypocretin-1, neuropeptide Y, leptin, ghrelin and adiponectin are implicated in both metabolic and sleep regulation, two conditions affected by OSA. We hypothesized that levels of these peptides may be related to EDS in OSA patients. METHODS: We included 132 patients with EDS, as defined by an Epworth Sleepiness Scale (ESS) score ≥ 13 (mean ± SD, 15.7 ± 2.3) and 132 patients without EDS as defined by an ESS score ≤ 9 (6.5 ± 1.9). All patients had an apnea-hypopnea index (AHI) ≥ 20 h(-1). Both groups were matched for gender (males; 83.3% vs. 85.6%), age (50.15 ± 11.2 yrs vs. 50.7 ± 9.9 yrs), body mass index (BMI) (31.8 ± 5.6 kg m(-2) vs. 32.1 ± 4.8 kg m(-2)), and apnea-hypopnea index (AHI) (45.5 ± 19.1 h(-1) vs. 43 ± 19.2 h(-1)). RESULTS: OSA patients with EDS showed significantly higher plasma hypocretin-1 levels (p < 0.001) and lower plasma ghrelin levels (p < 0.001) than OSA patients without EDS. There were no statistically significant differences in neuropeptide Y (p = 0.08), leptin (p = 0.07) and adiponectin (p = 0.72) between the two groups. In the multiple linear regression model ESS score was associated with plasma levels of hypocretin-1, ghrelin and total sleep time. CONCLUSION: Our study shows that EDS in patients with OSA is associated with increased circulating hypocretin-1 and decreased circulating ghrelin levels, two peptides involved in the regulation of body weight, energy balance, sympathetic tone and sleep-wake cycle. This relationship is independent of AHI and obesity (two key phenotypic features of OSA).