Effect of compliance to continuous positive airway pressure on exacerbations, lung function and symptoms in patients with chronic obstructive pulmonary disease and obstructive sleep apnea (overlap syndrome).

INTRODUCTION: Patients with overlap syndrome (OS), that is obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), are at increased risk of acute exacerbations related to COPD (AECOPD). We assessed the effect of CPAP compliance on AECOPD, symptoms and pulmonary function in OS patients. METHODS: Consecutive OS patients underwent assessment at baseline and at 12 months under treatment with CPAP of: AECOPD and hospitalizations, COPD Assessment Test (CAT) and modified British Medical Research Council (mMRC) questionnaires, pulmonary function testing and 6-min walking test (6MWT). RESULTS: In total, 59 patients (54 males) with OS were followed for 12 months and divided post hoc according to CPAP compliance into: group A with good (≥4 h CPAP use/night, n = 29) and group B with poor (<4 h CPAP use/night, n = 30) CPAP compliance. At 12 months, group A showed improvements in FEV1 (p = 0.024), total lung capacity (p = 0.024), RV/TLC (p = 0.003), 6MWT (p < 0.001) and CAT (p < 0.001). COPD exacerbations decreased in patients with good CPAP compliance from baseline to 12 months (17 before vs. 5 after, p = 0.001), but not in those with poor compliance (15 before vs. 15 after, p = 1). At multivariate regression analysis, COPD exacerbations were associated with poor CPAP compliance (ß = 0.362, 95% CI: 0.075-0.649, p = 0.015). CONCLUSIONS: When compared to poorly compliant patients, OS patients with good CPAP compliance had a lower number of AECOPD and showed improved lung function and COPD related symptoms.

Current and novel treatment options for obstructive sleep apnoea.

Obstructive sleep apnoea is a challenging medical problem due to its prevalence, its impact on quality of life and performance in school and professionally, the implications for risk of accidents, and comorbidities and mortality. Current research has carved out a broad spectrum of clinical phenotypes and defined major pathophysiological components. These findings point to the concept of personalised therapy, oriented on both the distinct clinical presentation and the most relevant pathophysiology in the individual patient. This leads to questions of whether sufficient therapeutic options other than positive airway pressure (PAP) alone are available, for which patients they may be useful, if there are specific indications for single or combined treatment, and whether there is solid scientific evidence for recommendations. This review describes our knowledge on PAP and non-PAP therapies to address upper airway collapsibility, muscle responsiveness, arousability and respiratory drive. The spectrum is broad and heterogeneous, including technical and pharmaceutical options already in clinical use or at an advanced experimental stage. Although there is an obvious need for more research on single or combined therapies, the available data demonstrate the variety of effective options, which should replace the unidirectional focus on PAP therapy.

European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea.

Treatment of obstructive sleep apnoea (OSA) in adults is evolving, as new therapies have been explored and introduced in clinical practice, while other approaches have been refined or reconsidered. In this European Respiratory Society (ERS) guideline on non-continuous positive airway pressure (CPAP) therapies for OSA, we present recommendations determined by a systematic review of the literature. It is an update of the 2011 ERS statement on non-CPAP therapies, advanced into a clinical guideline. A multidisciplinary group of experts, including pulmonary, surgical, dentistry and ear-nose-throat specialists, methodologists and patient representatives considered the most relevant clinical questions (for both clinicians and patients) relating to the management of OSA. Eight key clinical questions were generated and a systematic review was conducted to identify published randomised clinical trials that answered these questions. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the quality of the evidence and the strength of recommendations. The resulting guideline addresses gastric bypass surgery, custom-made dual-block mandibular advancement devices, hypoglossal nerve stimulation, myofunctional therapy, maxillo-mandibular osteotomy, carbonic anhydrase inhibitors and positional therapy. These recommendations can be used to benchmark quality of care for people with OSA across Europe and to improve outcomes.

European Respiratory Society statement on sleep apnoea, sleepiness and driving risk.

Obstructive sleep apnoea (OSA) is highly prevalent and is a recognised risk factor for motor vehicle accidents (MVA). Effective treatment with continuous positive airway pressure has been associated with a normalisation of this increased accident risk. Thus, many jurisdictions have introduced regulations restricting the ability of OSA patients from driving until effectively treated. However, uncertainty prevails regarding the relative importance of OSA severity determined by the apnoea-hypopnoea frequency per hour and the degree of sleepiness in determining accident risk. Furthermore, the identification of subjects at risk of OSA and/or accident risk remains elusive. The introduction of official European regulations regarding fitness to drive prompted the European Respiratory Society to establish a task force to address the topic of sleep apnoea, sleepiness and driving with a view to providing an overview to clinicians involved in treating patients with the disorder. The present report evaluates the epidemiology of MVA in patients with OSA; the mechanisms involved in this association; the role of screening questionnaires, driving simulators and other techniques to evaluate sleepiness and/or impaired vigilance; the impact of treatment on MVA risk in affected drivers; and highlights the evidence gaps regarding the identification of OSA patients at risk of MVA.

Clusters of sleep apnoea phenotypes: A large pan-European study from the European Sleep Apnoea Database (ESADA).

BACKGROUND AND OBJECTIVE: To personalize OSA management, several studies have attempted to better capture disease heterogeneity by clustering methods. The aim of this study was to conduct a cluster analysis of 23 000 OSA patients at diagnosis using the multinational ESADA. METHODS: Data from 34 centres contributing to ESADA were used. An LCA was applied to identify OSA phenotypes in this European population representing broad geographical variations. Many variables, including symptoms, comorbidities and polysomnographic data, were included. Prescribed medications were classified according to the ATC classification and this information was used for comorbidity confirmation. RESULTS: Eight clusters were identified. Four clusters were gender-based corresponding to 54% of patients, with two clusters consisting only of men and two clusters only of women. The remaining four clusters were mainly men with various combinations of age range, BMI, AHI and comorbidities. The preferred type of OSA treatment (PAP or mandibular advancement) varied between clusters. CONCLUSION: Eight distinct clinical OSA phenotypes were identified in a large pan-European database highlighting the importance of gender-based phenotypes and the impact of these subtypes on treatment prescription. The impact of cluster on long-term treatment adherence and prognosis remains to be studied using the ESADA follow-up data set.

Gender Differences in Obstructive Sleep Apnea: The Value of Sleep Questionnaires with a Separate Analysis of Cardiovascular Patients.

BACKGROUND: Gender affects the clinical presentation of obstructive sleep apnea (OSA). The classic OSA symptoms, such as sleepiness, snoring, and apnea, are not so frequent in women. OBJECTIVES: To evaluate possible gender differences in questionnaires used for OSA prediction, such as the Epworth Sleepiness Scale (ESS), STOP, STOP Bang (SB), Berlin Questionnaire (BQ), Athens Insomnia Scale (AIS), and Fatigue Scale (FS). METHODS: 350 males were matched with 350 women referred to a sleep clinic, according to OSA severity. All responded to the questionnaires and underwent a sleep study. Cardiovascular disease (CVD) patients were separately analyzed. RESULTS: ESS did not differ between genders. SB was higher in males, whereas STOP, BQ, AIS, and FS were higher in females. BQ presented the highest sensitivity in both genders, whereas STOP exhibited the highest specificity in males and ESS in females. AIS and FS were more sensitive and SB more specific in females, whereas BQ was more specific in males. For severe OSA, the predictive values of SB and BQ were almost similar for both genders; however AIS and FS were higher in women. CVD patients presented higher scores, independent of gender, except for AIS, which was higher in females. CONCLUSION: Gender-specific evaluation of questionnaires is necessary to prevent OSA under-diagnosis.

Central sleep apnoea and periodic breathing in heart failure: prognostic significance and treatment options.

Central sleep apnoea (CSA) including periodic breathing is prevalent in more than one-third of patients with heart failure and is highly and independently associated with poor outcomes. Optimal treatment is still debated and well-conducted studies regarding efficacy and impact on outcomes of available treatment options are limited, particularly in cardiac failure with preserved ejection fraction. While continuous positive airway pressure and oxygen reduce breathing disturbances by 50%, adaptive servoventilation (ASV) normalises breathing disturbances by to controlling the underlying mechanism of CSA. Results are contradictory regarding impact of ASV on hard outcomes. Cohorts and registry studies show survival improvement under ASV, while secondary analyses of the large SERVE-HF randomised trial showed an excess mortality in cardiac failure with reduced ejection fraction. The current priority is to understand which phenotypes of cardiac failure patients may benefit from treatment guiding individualised and personalised management.

Sleep in chronic respiratory disease: COPD and hypoventilation disorders.

COPD and obstructive sleep apnoea (OSA) are highly prevalent and different clinical COPD phenotypes that influence the likelihood of comorbid OSA. The increased lung volumes and low body mass index (BMI) associated with the predominant emphysema phenotype protects against OSA whereas the peripheral oedema and higher BMI often associated with the predominant chronic bronchitis phenotype promote OSA. The diagnosis of OSA in COPD patients requires clinical awareness and screening questionnaires which may help identify patients for overnight study. Management of OSA-COPD overlap patients differs from COPD alone and the survival of overlap patients treated with nocturnal positive airway pressure is superior to those untreated. Sleep-related hypoventilation is common in neuromuscular disease and skeletal disorders because of the effects of normal sleep on ventilation and additional challenges imposed by the underlying disorders. Hypoventilation is first seen during rapid eye movement (REM) sleep before progressing to involve non-REM sleep and wakefulness. Clinical presentation is nonspecific and daytime respiratory function measures poorly predict nocturnal hypoventilation. Monitoring of respiration and carbon dioxide levels during sleep should be incorporated in the evaluation of high-risk patient populations and treatment with noninvasive ventilation improves outcomes.

Use of the Clinical Global Impression scale in sleep apnea patients - Results from the ESADA database.

OBJECTIVE/BACKGROUND: The Clinical Global Impression scale (CGI) reflects the clinician's assessment of the disease impact on patient's global functioning. We assessed predictors of CGI scale rating in patients with obstructive sleep apnea (OSA). PATIENTS/METHODS: Consecutive patients with suspected OSA (n = 7581) were identified in the European Sleep Apnea Database (ESADA). Anthropometrics, comorbidities, apnea severity obtained by polygraphy or polysomnography, and daytime sleepiness [Epworth Sleepiness Scale (ESS)] were assessed. The CGI 7-point scale was completed at the end of the diagnostic process (CGI-severity, ie, CGI-S) and, in a subpopulation, at treatment follow-up (CGI-Improvement). RESULTS: CGI-S was rated mild to moderate in 44% of patients. CGI rating at any given apnea intensity was worse in women than in men (p < 0.01). Patients undergoing polygraphy (n = 5075) were more frequently rated as severely ill compared to those studied with polysomnography (19.0% vs 13.0%, p < 0.001). In patients aged ≤65 years, CGI scoring was generally better than in the elderly despite a similar degree of OSA (eg, 'normal, not ill' 24.2% vs 15.3%, p < 0.01, respectively). Independent predictors of CGI rating included age, BMI, AHI, ESS, cardio-metabolic comorbidities, and diagnosis based on polygraphy. CGI-improvement rating (Beta = -0.406, p < 0.01) was superior to sleep apnea severity or ESS-score (Beta = 0.052 and -0.021, p = 0.154 and 0.538 respectively) at baseline for prediction of good CPAP compliance at follow-up. CONCLUSIONS: CGI rating is confounded by gender, age class and the type of sleep diagnostic method. As OSA phenotypes differ, CGI may contribute as a clinical tool to reflect the significance of clinical disease.

Change in weight and central obesity by positive airway pressure treatment in obstructive sleep apnea patients: longitudinal data from the ESADA cohort.

The effect of positive airway pressure treatment on weight and markers of central obesity in patients with obstructive sleep apnea remains unclear. We studied the change in body weight and anthropometric measures following positive airway pressure treatment in a large clinical cohort. Patients with obstructive sleep apnea with positive airway pressure treatment from the European Sleep Apnea Database registry (n = 1,415, 77% male, age 54 ± 11 [mean ± SD] years, body mass index 31.7 ± 6.4 kg/m2 , apnea-hypopnea index 37 ± 24 n per hr, Epworth Sleepiness Scale 10.2 ± 5.0) were selected. Changes in body mass index and neck/waist/hip circumferences at baseline and at follow-up visit were analysed. Overall, body mass index (0.0 [95% confidence interval, -0.1 to 0.2] kg/m2 ) and neck circumference (0.0 (95% confidence interval, -0.1 to 0.1] cm) were unchanged after positive airway pressure treatment compared with baseline (follow-up duration 1.1 ± 1.0 years and compliance 5.2 ± 2.1 hr per day). However, in non-obese (body mass index <30 kg/m2 ) patients, positive airway pressure treatment was associated with an increased body mass index and waist circumference (0.4 [0.3-0.5] kg/m2 and 0.8 [0.4-1.2] cm, respectively, all p < 0.05), and weight gain was significantly associated with higher positive airway pressure compliance and longer positive airway pressure treatment duration. In the obese subgroup, body mass index was reduced after positive airway pressure treatment (-0.3 [-0.5 to -0.1] kg/m2 , p < 0.05) mainly in patients with a strong reduction in Epworth Sleepiness Scale. In conclusion, positive airway pressure therapy was not found to systematically change body mass index in the European Sleep Apnea Database cohort, but the response was heterogeneous. Our findings suggest that weight gain may be restricted to an obstructive sleep apnea phenotype without established obesity. Lifestyle intervention needs to be considered in both lean and obese patients with obstructive sleep apnea receiving positive airway pressure treatment.

Molecular profiling of EGFR family in chronic obstructive pulmonary disease: correlation with airway obstruction.

BACKGROUND: Growth factors mediate various cellular responses to environmental stimuli. Specifically, exposure of lung epithelium to oxidative stress induced by cigarette smoke stimulates aberrant epidermal growth factor receptor (ERBB) family activation. This study's objective was to evaluate the expression of ERBB1-4 receptors in the lung tissue of smokers with or without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: ERBBs expression was measured by microarray analysis in lung tissue samples from five patients with COPD and five non-COPD smokers, and by quantitative real-time PCR in additional 20 patients with COPD (GOLD stage II), 15 non-COPD smokers and 10 nonsmoker controls. RESULTS: Microarray data analysis revealed that ERBB receptors expression was elevated in patients with COPD compared to non-COPD smokers, ranging from 1·62- to 2·45-fold, (P < 0·01). Real-time qPCR verified that patients with COPD had higher ERBB1-3 expression levels compared with non-COPD smokers (PERBB1  < 0·001; PERBB2  = 0·003; PERBB3  = 0·003) and nonsmokers (PERBB1  = 0·019; PERBB2  = 0·005; PERBB3  = 0·011). On the other hand, ERBB4 mRNA levels gradually increased from nonsmokers (0·74 ± 0·19) to non-COPD smokers (1·11 ± 0·05) to patients with COPD (1·57 ± 0·28) and were correlated with the degree of airflow obstruction (PFEV1  < 0·001). DISCUSSION: These data suggest that ERBB1-3 overexpression is not related only to smoking exposure but probably to epithelial remodelling and mucociliary system distortion, characterizing COPD. Additionally, the inverse correlation of ERBB4 with FEV1 exhibits a possible link between ERBB4 and COPD severity.

Evidence of dysregulated affect indicated by high alexithymia in obstructive sleep apnea.

Alexithymia refers to dysregulation of affect characterized by difficulty in identifying and expressing emotions. Obstructive sleep apnea (OSA) is characterized by increased medical/psychiatric comorbidity and possibly by affect dysregulation. In the present case-control study, we examined alexithymia levels with the Toronto Alexithymia Scale (TAS-20) in 23 psychiatrically uncomplicated OSA outpatients and 23 same gender controls one-to-one matched for age, education and subjective depressive symptomatology. General health/quality of life was assessed with the Short-Form 36 Health Survey (SF-36) in the patient group. Hierarchical multivariate regression models were used to evaluate the association of alexithymia with the presence of OSA, and clinical and polysomnographic parameters of this condition. TAS-20 total and subscale scores were associated positively with Beck Depression Inventory (BDI)-21 and negatively with SF-36 scores. After adjusting for all confounders, OSA was positively associated with total TAS-20 score, 'expressing feelings' and 'externally oriented thinking' subscales. The latter was associated with increased sleepiness and reduced blood oxygenation in the OSA group. Finally, 'difficulty describing feelings' and 'externally oriented thinking' significantly predicted risk for OSA. Alexithymia is higher in non-psychiatrically ill patients with OSA compared with carefully matched controls even after adjustment for subjective depressive symptoms and demographic confounders. Total alexithymia is associated with greater subjective depression and poor general health/quality of life, while 'externally oriented thinking' is associated with disease severity and together with 'difficulty describing feelings' may be vulnerability factors for OSA, although reverse causality cannot be excluded.

Angiogenic molecule Tie-2 and VEGF in the pathogenesis of pleural effusions.

BACKGROUND: The role of angiogenesis in the pathogenesis of pleural effusion (PE) has not been determined. The expression of angiogenic factors may represent useful markers for the diagnosis and prediction of disease outcome. To measure the pleural fluid (PF) and serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and Tie receptor tyrosine kinase (Tie-2) in order to investigate their role in the pathogenesis of PEs. METHODS: Sixty-seven, 17 with transudative PEs due to heart failure and 50 with exudative PEs (malignant, 22; inflammatory, 15; undiagnosed, 13) were included in the study. PF and serum levels of the growth factors (VEGF, bFGF and Tie-2) were measured using enzyme-linked immunosorbent assays. RESULTS: PF and serum VEGF levels but not bFGF and Tie-2 levels were higher (p<0.005) in exudates than in transudates. PF VEGF levels were significantly higher in malignant than inflammatory and undiagnosed PEs (p=0.03). In addition, PF Tie-2 levels were not found different in malignant or in parapneumonic PEs. CONCLUSION: Our results showed that VEGF is one of the main mediators in exudative PEs, but this effect is not mediated through the angiogenetic pathway Ang-1/Tie-2. However, the role of angiogenesis and its pathways in the pathogenesis of exudative PEs needs further exploration.

Laser-assisted uvulopalatoplasty for the treatment of snoring and mild obstructive sleep apnea syndrome.

OBJECTIVE: To determine the efficacy of the laser-assisted uvulopalatoplasty (LAUP) procedure on snoring and Apnea-Hypopnea-Index (AHI) improvement in patients with snoring and mild obstructive sleep apnea syndrome (OSAS). STUDY DESIGN: Prospective, nonrandomized, nonblinded assessment of outcomes after LAUP in patients suffering from benign habitual snoring and/or mild OSAS. METHODS: Fifty-nine patients with habitual snoring and 25 patients with mild OSAS underwent LAUP (6 of them underwent simultaneous classic tonsillectomy and 20 carbon-dioxide laser tonsillotomy). All patients and their bed partners completed pre- and post-treatment questionnaires ranking snoring, whereas the patients with mild OSAS underwent postoperative polysomnography (PSG). RESULTS: During a 6-month to 5-year follow-up (mean 40 months), 91.5% of the patients with habitual snoring reported significant short-term improvement based on post-treatment questionnaires, whereas 79.7% reported long-term subjective improvement. Nineteen of 25 patients (76%) with mild OSAS reported significant improvement of snoring based on posttreatment questionnaires. According to the postoperative PSG, only 2% showed a worse AHI, whereas 60% showed reduction of the AHI to < or = 5. Eight patients (32%) showed little or no improvement of AHI. CONCLUSIONS: LAUP, in combination with carbon-dioxide laser tonsillotomy in some cases, is a safe, cost-effective, outpatient procedure for the treatment of many cases of habitual snoring and mild OSAS when preceded by careful selection of the candidates.