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Purpose Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function. Methods We conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP. Results Nineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI − 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP. Conclusions CPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function. ISRCTN 78082983, 23/10/2014, Prospectively registered.

Introduction The severity of obstructive sleep apnoea (OSA) is highly variable on a night-to-night basis. Patients are commonly categorised based on the severity of their OSA, and this is then used to influence management and reimbursement, including continuous positive airway pressure (CPAP). We aimed to establish to what extent the OSA severity category changes during two periods of OSA, based on mean and maximum oxygen desaturation index (ODI). Methods Patients with a diagnosis of moderate to severe OSA who had been on CPAP for greater than 1 year were included in this study. Subjects underwent two periods of CPAP withdrawal for four nights each. Results Twenty-five patients completed the study. Based on the mean ODI of the four nights, 14 (56%) patients changed OSA severity categorisation, with three (12%) changing category to mild. Based on the maximum ODI of the four nights, nine (36%) patients changed OSA severity categorisation, with one (4%) changing category to mild. One third to a half of patients’ OSA severity category changed between the two periods of four night’s CPAP withdrawal. Conclusions OSA is highly variable on a period-to-period basis as well as on a night-to-night basis. We believe the concept of patients having a definable and ‘real’ level of OSA severity is therefore flawed. OSA severity should be based mainly on symptoms, as these are the dominant reasons for treatment, and the sleep study should be used qualitatively to ascertain whether respiratory events are the likely cause of the symptoms. Trial Registration ISRCTN17987510.

For obstructive sleep apnoea (OSA), few mechanical treatment options are available and no pharmacotherapy is approved [1–3]. However, safe and efficacious pharmacotherapy would have substantial appeal for many people with OSA., BAY 2253651 is a nasally applied genioglossus muscle activator via pharyngeal mucosal receptor stimulation (potassium channel blocker) aimed to treat obstructive sleep apnoea. Although well-tolerated and safe, there was no significant therapeutic effect. https://bit.ly/3zDbyia

Damage to the blood vessels supplying the lung accompanies several systemic disorders, and their classification can be confusing. This chapter clearly explains the different presentations, the different blood tests available, and the pathology (mainly based on size of vessel involved) associated with diseases such as granulomatosis with polyangiitis (Wegener’s), microscopic polyangiitis, Goodpasture’s disease, Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis), and the rarer arteritides such as Takayasu’s.

These common infections are typically self-limiting and managed in the community but, in the immunocompromised, can be devastating (especially with suppressed T-cell function such as following organ transplant). Viral pathogens discussed include influenza, cytomegalovirus (CMV), adenovirus, measles, human metapneumovirus, parainfluenza, respiratory syncitial virus (RSV), varicella pneumonia, hantavirus. Severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) are covered and reflect recent developments. The circumstances surrounding these infections and appropriate laboratory tests are discussed in detail, as imaging of the lung is rarely diagnostic.

This chapter covers all aspects of the diagnosis and management of community and hospital acquired pneumonia. Community-acquired pneumonia represents the commonest infectious cause of death in the UK and USA. Up to 10% require ITU admission where mortality remains at 50%. The predisposing conditions are discussed. This chapter includes guidance on community-acquired pneumonia severity scores and antibiotic choice, based on the recent British Thoracic Society guidelines. Strategies for patients who may need ITU care, who fail to respond to initial antibiotics, and who need follow-up after pneumonia are discussed. Other forms of respiratory infection are covered, including their aetiology and their management. These include ventilator-acquired pneumonia (VAP), aspiration pneumonia, lung abscess (including Lemierre’s syndrome), nocardiosis, actinomycosis, anthrax, tularaemia, melioidosis, and leptospirosis. The differential diagnosis of fever and CXR infiltrates in a patient on ITU is highlighted.

This chapter covers three diagnostic tests in common use that are not described elsewhere in this Handbook. Skin prick tests are still used, although some units have replaced them with the more expensive RAST tests for specific IgE. A full description of how to do and read them is included. The simple technique of induced sputum for TB and PCP is less frequently used although likely to increase in use as specific new biomarkers of disease are identified in sputum. Bronchoprovocation testing to measure bronchial reactivity is also done by many units to help in the diagnosis of asthma, and a full description of the various techniques is included in this chapter.

The aim of pleurodesis is to seal visceral to parietal pleura with adhesions to prevent pleural fluid or air accumulating. Pleurodesis is dependent upon lung re-expansion following removal of pleural fluid or air, which allows the apposition of visceral and parietal pleura. This may be encouraged by applying suction to an intercostal drain. Inflammation of the pleural surfaces and local activation of coagulation, required to produce pleural fibrosis and adhesions. May be induced by chemical sclerosing agent or by mechanical pleural abrasion at VATS.

This chapter considers pneumothorax aspiration. 1° pneumothorax: Consider aspiration if patient breathless, hypoxic, and pneumothorax large. 2° pneumothorax: Consider aspiration if evidence of underlying lung disease (or patient with significant smoking history, aged >50 years), with small pneumothorax and breathlessness.

Includes: Indications and risks, bleeding and bronchoscopy, patient preparation, bronchial washings, bronchial brushings, bronchial biopsies, bronchoalveolar lavage (BAL), transbronchial lung biopsy (TBB), central airway obstruction, diagnostic procedures, TBNA, EBUS, Radial EBUS, autofluorescence bronchoscopy, rigid bronchoscopy, navigation bronchoscopy, therapeutic procedures, bronchial laser resection, electrocautery, argon–plasma coagulation (APC), and cryotherapy/cryoextraction, photodynamic therapy (PDT), tracheobronchial stent insertion, and rachytherapy.

Thoracic ultrasound (TUS) is increasingly used for bedside evaluation of the pleural space and thorax. Given improved safety, NPSA and BTS guidance ‘strongly recommend’ TUS for pleural fluid procedure site selection. TUS also gives useful diagnostic information that may alter management (e.g. a patient with a transudative effusion who has pleural nodularity, suggestive of malignancy).

Includes: Positive pressure ventilators, CPAP, high-flow nasal oxygen (HFNO), indications, acute exacerbation of COPD, acute cardiogenic pulmonary oedema, decompensated OSA and obesity hypoventilation, respiratory failure from neuromuscular weakness, Immunocompromised patients, CAP, contraindications, chest wall deformity and neuromuscular weakness, sleep apnoea, cystic fibrosis, COPD, NIV end-of-life weaning

Includes: Simple airway adjuncts, oropharyngeal airway (Guedel), nasopharyngeal airway, supra-glottic airway devices (SGAD), intubation, endotracheal tube

Many fungi can affect the lung through direct invasion or immunological mechanisms. This chapter covers the range of fungi and the mechanisms by which they can cause damage, as well as the factors provoking invasion, such as immunosuppression, HIV, infection, bone marrow suppression, and use of biological therapies like infliximab. Aspergillus is the most common and covered in detail, including simple allergic asthma, allergic bronchopulmonary aspergillosis, invasive Aspergillus disease, aspergilloma, and hypersensitivity pneumonitis due to Aspergillus. The role of steroids and antifungal agents is explored. Pneumocystis pneumonia (PCP) is also covered in detail, particularly its treatment in different settings. The endemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis and paracoccidioidomycosis), cryptococcosis, and candidal pneumonia are all discussed, with sections on their presentation, diagnosis, and treatment.

Immunosuppressive drugs are used mainly in the management of pulmonary vasculitis, but also in asthma, sarcoidosis, and ILD. The chapter also covers corticosteroids, azathioprine, methotrexate, cyclophosphamide, rituximab

Using image guidance (either CT or US), a cutting needle takes several 1–2 cm cores along the long axis of any parietal pleural pathology. PET/CT may have a role guiding pleural biopsy in patients with diffuse pleural abnormality to increase sensitivity. US-guided pleural biopsies increase microbiological diagnosis in pleural infection but this is not routine practice. Using thoracoscopic biopsy (medical thoracoscopy/VATS), multiple biopsies are taken of visually abnormal parietal pleura. Using a pleural biopsy needle in a ‘blind’ percutaneous fashion to take multiple biopsies. Not advocated for diagnosing malignancy. May have utility in resource-limited settings for diffuse pleural diseases, but thoracoscopy still preferred.

Background: The efficacy of CPAP at the mildest end of the OSA spectrum is unclear. The MERGE trial investigated the effect of CPAP on quality of life in patients with mild OSA (Wimms et al. 2019). This subset analysis aimed to determine the effectiveness of CPAP in a subset of patients with ‘very9 mild OSA, defined as having mild OSA according to the sensitive AASM 2012 criteria, but no OSA using the earlier AASM 2007 criteria (i.e. AHI >5 to Methods: The MERGE trial randomised patients with mild OSA (AHI >5 to ≤15 events/hr, AASM 2007 or 2012) in parallel to receive either CPAP plus Standard Care or Standard Care alone for 3 months. A subset of 95 of 301 patients were identified as having ‘very9 mild OSA. Results: The subset of 95 ‘very9 mild OSA patients had a median (IQR) AHI 6.80(5.7, 8.8) events/hr, and were symptomatic (Vitality 41.9(10.9); ESS 10.3(4.7)). 50 of 95 were allocated to CPAP, and 45 to Standard Care. ‘Very9 mild OSA patients had significantly improved Vitality after 3 months of CPAP, compared to Standard Care (+9.2 points, 95% CI +5.6 to +12.7; p Conclusions: This subset analysis has shown the clinical effectiveness of CPAP treatment in patients at the mildest end of the disease spectrum, with 9very9 mild but symptomatic OSA. The results were similar to those observed in the primary analysis of the MERGE trial.

Background and objective Obstructive sleep apnoea (OSA) is associated with cardiovascular disease. Intermittent hypoxia, endothelial dysfunction and adipose tissue-mediated inflammation have all been linked to cardiovascular disease in OSA. We therefore explored the effect of OSA on relevant associated blood markers: adrenomedullin (ADM), endocan, endothelin-1 (ET-1), resistin and vascular endothelial growth factor (VEGF). Methods Patients with OSA, established on and compliant with continuous positive airways pressure (CPAP) therapy for >1 year were included from three randomized controlled trials, conducted at two centres. Patients were randomized to either continued therapeutic CPAP or sham CPAP (CPAP withdrawal) for 2 weeks. Blood markers were measured at baseline and at 14 days and the treatment effect between sham CPAP and therapeutic CPAP was analysed. Results A total of 109 patients were studied (therapeutic CPAP n = 54, sham CPAP n = 55). Sham CPAP was associated with a return of OSA (between-group difference in oxygen desaturation index (ODI) 36.0/h, 95% CI 29.9-42.2, P Conclusion Whilst CPAP withdrawal was associated with return of OSA, it was associated with an unexpected significant reduction in the vasodilator ADM and not with expected increases in hypoxia-induced markers, markers of endothelial function or resistin. We propose that the vascular effects occurring in OSA may be brought about by other mechanisms, perhaps partly through a reduction in ADM.

We previously published data in the European Respiratory Journal describing the return of obstructive sleep apnoea (OSA) following the withdrawal of continuous positive airway pressure (CPAP) [1]. In this study, about one third of patients did not experience a significant return of OSA by the fourth night without CPAP, as measured using the oxygen desaturation index (ODI). This suggested that CPAP need not be an every night therapy in some patients with OSA, although there was no clear way of identifying such patients in advance of the trial of CPAP withdrawal. Limitations to this study were discussed in the paper and correctly highlighted by van Zeller and Drummond [2].

We thank Dr. Jaster for reading our articles with interest and sharing his thoughts on the potential impacts of untreated obstructive sleep apnoea (OSA) and continuous positive airway pressure (CPAP) effects on medullary brain nuclei. There are three topics we would like to address: (I) the hypothesis of an association between OSA and ischemic pathology of medullary brain nuclei and a potential exacerbation by CPAP, (II) the different roles of pCO2 in OSA and central sleep apnoea (CSA), and (III) the effects of a short-term CPAP withdrawal on the brain and the heart.

The effect of continuous positive airway pressure (CPAP) on cardiovascular events is uncertain in minimally symptomatic obstructive sleep apnoea. Previous 2-year follow-up data from the Multicentre Obstructive Sleep Apnoea Intervention Cardiovascular (MOSAIC) trial showed a marginal reduction in cardiovascular events with CPAP therapy. We now present long-term MOSAIC study follow-up data. Median (first quartile, third quartile) follow-up was 5.0 (2.2, 5.0) and 3.7 (1.5, 5.0) years for CPAP and standard care, respectively. Compared to standard care, CPAP had no statistically significant effect on the risk of cardiovascular events (HR=0.83, p=0.54, 95% CI 0.46–1.51).

Introduction: The observation that oxygen desaturations do not necessarily return during CPAP withdrawal has been used to suggest that CPAP may not need to be an every night treatment. We explored the possibility that heart rate rises may return before oxygen desaturations; suggesting that sleep fragmentation may still be a problem. Methods: We analysed pulse oximetry data from 92 patients with OSA undergoing CPAP withdrawal (3 nights on CPAP followed by 4 nights off CPAP). The nightly oxygen desaturation index ≥4% (ODI) and heart rate rises >6bpm index (HRR), were assessed during CPAP withdrawal using ANOVA and Fisher’s post hoc tests; in all patients, and in a subset of 27 patients with gradual ODI return. Results: In the whole group the ODI and HRR increased equivalently and maximally on the first night off CPAP (Off CPAP 1; ODI=87% and HRR=104% of Off CPAP 4). In a subset with gradual ODI return, HRR returned rapidly (Off CPAP 1; ODI=43% and HRR=77% of Off CPAP 4; see table). Nightly pulse oximetry from 27 patients with gradual ODI return. Both ANOVA tests were significant (p Discussion: During CPAP withdrawal, in some patients, heart rate rises return before oxygen desaturations. This suggests that ODI alone may fail to adequately identify patients in whom potentially symptomatic OSA returns off CPAP.

Obstructive sleep apnea (OSA) is associated with systemic hypertension. Either overnight intermittent hypoxia, or the recurrent arousals that occur in OSA, could cause the daytime increases in blood pressure (BP).To establish the role of intermittent hypoxia in the increased morning BP in patients with OSA.Randomized, double-blinded, crossover trial assessing the effects of overnight supplemental oxygen versus air (sham) on morning BP, after continuous positive airway pressure (CPAP) withdrawal in patients with moderate to severe OSA. The primary outcome was the change in home morning BP after CPAP withdrawal for 14 nights, oxygen versus air. Secondary outcomes included oxygen desaturation index (ODI), apnea-hypopnea index (AHI), subjective sleepiness (Epworth Sleepiness Scale score), and objective sleepiness (Oxford Sleep Resistance Test).Supplemental oxygen virtually abolished the BP rise after CPAP withdrawal and, compared with air, significantly reduced the rise in mean systolic BP (-6.6 mm Hg; 95% confidence interval [CI], -11.3 to -1.9; P = 0.008), mean diastolic BP (-4.6 mm Hg; 95% CI, -7.8 to -1.5; P = 0.006), and median ODI (-23.8/h; interquartile range, -31.0 to -16.3; P 0.001) after CPAP withdrawal. There was no significant difference, oxygen versus air, in AHI, subjective sleepiness, or objective sleepiness.Supplemental oxygen virtually abolished the rise in morning BP during CPAP withdrawal. Supplemental oxygen substantially reduced intermittent hypoxia, but had a minimal effect on markers of arousal (including AHI), subjective sleepiness, or objective sleepiness. Therefore intermittent hypoxia, and not recurrent arousals, appears to be the dominant cause of daytime increases in BP in OSA.

Obstructive sleep apnoea (OSA) is increasing in prevalence due to rising obesity. While OSA is a disorder primarily of the upper airway during sleep, its pathophysiological impact on other body systems is increasingly recognised. There has been interest in the prevalence of OSA in different ophthalmic conditions and possible causation has been postulated. As OSA is common, it can be expected that people with co-existent OSA will be found in any ophthalmic disease population studied. To determine with confidence the significance of finding patients with OSA in a particular cohort requires a well matched control group, ideally matched for age, obesity, gender and co-morbidities. Only if one can say with certainty that the prevalence of OSA is higher in a group with a particular co-existent ophthalmic disease can we begin to speculate about possible mechanisms for the overlap in these conditions. Possible mechanisms for how OSA might affect the eye are discussed in this review. The current literature is reviewed with respect to diabetic retinopathy, glaucoma, floppy eyelid syndrome, non-arteritic ischaemic optic neuropathy, keratoconus and AMD. Associations with OSA have been found, but robust prospective studies using multi-channel sleep studies to diagnose OSA are lacking. Gaps remain in the evidence and in our knowledge. It is hoped that this review will highlight the need for ophthalmologists to consider OSA in their patients. It also makes recommendations for future research, especially to consider whether therapies for OSA can also be effective for ophthalmic disorders.

Introduction: Oxidative stress is thought to be important in the development of cardiovascular disease in OSA. However, our unit recently reported no increases in biomarkers of oxidative stress in OSA with an unexpected reduction in urinary F2-isoprostanes (F2ISO) 1 . These urinary measurements were made on early morning urinary samples which may have missed any rise resulting from the OSA occurring during the night. We aimed to test the hypothesis that overnight urinary F2ISO levels are increased, and that early morning levels may thus be misleading. Methods: Patients had OSA with an ODI > 20, used CPAP for > 1 year and > 4 h/n. Patients were randomised to 2 weeks of either sham CPAP or continuing CPAP. Overnight urine collections were carried out by patients at baseline and after two weeks. Urinary F2ISO levels were measured by ELISA technique and adjusted for age, gender, BMI, smoking status, statin use, anti-hypertensive use and urine creatinine. Results: 23 patients were enrolled with 12 randomised to sham CPAP and 11 to CPAP. Patients were well matched for age, gender, BMI, smoking status and statin therapy. More patients in the sham CPAP arm were on antihypertensive medication (58% vs 46%). There was a significant reduction in overnight urinary F2ISO with sham CPAP compared with continuing CPAP (adjusted treatment effect -1.2 ng/ml, 95%CI -2.1 to -0.2, p=0.02). Discussion: Overnight urinary F2ISO were reduced with return of OSA, as in our original study using early morning urines, further suggesting that oxidative stress is not increased by OSA. 1.ERJ 2015:46:1065-71.

Purpose Obesity is associated with both obstructive sleep apnea (OSA) and obesity hypoventilation. Differences in adipose tissue distribution are thought to underlie the development of both OSA and hypoventilation. We explored the relationships between the distribution of upper airway, neck, chest, abdominal and muscle fat in very obese individuals. Methods We conducted a cross-sectional cohort study of individuals presenting to a tertiary sleep clinic or for assessment for bariatric surgery. Individuals underwent magnetic resonance (MR) imaging of their upper airway, neck, chest, abdomen and thighs; respiratory polygraphy; 1 week of autotitrating CPAP; and morning arterial blood gas to determine carbon dioxide partial pressure and base excess. Results Fifty-three individuals were included, with mean age of 51.6 ± 8.4 years and mean BMI of 44.3 ± 7.9 kg/m2; there were 27 males (51%). Soft palate, tongue and lateral wall volumes were significantly associated with the AHI in univariable analyses (p Conclusions In very obese individuals, our results indicate that increased volumes of upper airway structures are associated with increased severity of OSA, as previously reported in less obese individuals. Increasingly large upper airway structures that reduce pharyngeal lumen size are likely to lead to OSA by increasing the collapsibility of the upper airway. However, we did not show any significant association between regional fat distribution and propensity for hypoventilation, in this population.

Introduction Intermittent hypoxia and/or intermittent arousals are thought to be the two key pathological mechanisms in the development of hypertension in obstructive sleep apnoea (OSA). We aimed to investigate the effect of abolishing the hypoxia on the rise in blood pressure (BP) that has been shown to follow continuous positive airway pressure (CPAP) withdrawal in patients with OSA. In addition, we explored the effect of supplemental oxygen on obstructive events during sleep. Methods Patients with OSA, established on CPAP≥1 year, and with ≥4 hours/ night usage, underwent a week of screening oximetry and were eligible if they had a nocturnal oxygen desaturation index ≥4% (ODI) of Results Twenty-five patients completed the study. Their mean ±standard deviation age was 63±7 years, mean BMI was 35.3±6.7 kg/m2, median (interquartile range) ODI at diagnosis was 48/hour (25, 68), and 21 (84%) were male. Table 1 shows the Results of the primary outcome and the overnight sleep studies. Discussion Supplemental oxygen abolished the rise in early morning blood pressure during CPAP withdrawal when compared to supplemental air. As expected, supplemental oxygen substantially attenuated intermittent hypoxia and had only a small non-significant effect on the apnoea hypopnoea index. Thus intermittent hypoxia appears to be the dominant determinant of the rise in morning blood pressure seen in patients with OSA, rather than any other consequence of the obstructive events.

Obstructive sleep apnoea (OSA) is a common disorder and is associated with cardiovascular disease. Continuous positive airway pressure, whilst reducing blood pressure, has not been shown to reduce cardiovascular events when used as a treatment solely for this purpose in patients with previous cardiovascular disease. Developing a better understanding of the mechanisms underlying cardiovascular disease in OSA is important to develop new treatments. Potential causative mechanisms for cardiovascular disease in OSA include arousal induced sympathetic activation, large intrathoracic pressure swings leading to shear stress on the heart and great vessels, and intermittent hypoxia. This review discusses the role of intermittent hypoxia, as a major physiological consequence of OSA, in the development of cardiovascular disease.

One night of a sleep study is the standard for diagnosis and exclusion of obstructive sleep apnea. Single testing requires high sensitivity of the test method and a stable disease of interest to warrant a low rate of false-negative tests. Obstructive sleep apnea is diagnosed and graded by conventional thresholds of apneas and hypopneas per hour of sleep, and treatment is usually initiated in the presence of symptoms. The aim of this study was to assess night-to-night variability of obstructive sleep apnea to reassess the current practice. Seventy-seven patients previously diagnosed with obstructive sleep apnea, randomised to continuous positive airway pressure withdrawal within four trials, performed nightly pulse-oximetry over 2 weeks while off continuous positive airway pressure. The main outcome of interest was the coefficient of variation of the oxygen desaturation index marking night-to-night variability in obstructive sleep apnea. Obstructive sleep apnea was categorised according to conventional thresholds using oxygen desaturation index (no obstructive sleep apnea:5 per h; mild: 5-15 per h; moderate: 15-30 per h; and severe:30 per h). High night-to-night variability of obstructive sleep apnea was evidenced by a coefficient of variation of oxygen desaturation index of 31.1% (SD 16.5). Differences in oxygen desaturation index of10 per h between nights were found in 84.4% and shifts in obstructive sleep apnea severity category in 77.9% of patients. The probability of missing moderate obstructive sleep apnea was up to 60%. Variability was higher in less severe obstructive sleep apnea. Obstructive sleep apnea shows a considerable night-to-night variability. Single-night diagnostic sleep studies are prone to miscategorise obstructive sleep apnea if arbitrary thresholds are used. Thus, treatment decisions should be based less on the conventional derivatives from sleep studies, especially in patients with less severe obstructive sleep apnea.www.controlled-trials.com (ISRCTN 93153804, ISRCTN 73047833) and www.clinicaltrials.gov (NCT01332175NCT02050425).

Screening tests are widely used, either in low disease prevalence populations, e.g., breast cancer screening, or more focused screening in patients declaring symptoms suggestive of a disease, such as CT coronary angiography for patients with chest pain. Three papers in this journal look at screening for obstructive sleep apnea (OSA) using questionnaires in varied populations with very different prevalences of OSA [1]; [2] ; [3]. However, there is surprisingly little evidence that such activities are valuable, or that they should divert resources away from patients with symptomatic OSA.

Introduction: The causes of cardiovascular disease in OSA are not fully established. The predominant mechanisms of vascular damage in OSA could be either intermittent hypoxia (IH), arousal induced sympathetic activation or excessive pleural pressure swings. Thus, we investigated the effects of CPAP withdrawal on two cardiovascular markers induced by hypoxia via hypoxia inducible factor (HIF) activation: adrenomedullin (ADM, an endothelial-derived vasodilator) and vascular endothelial growth factor (VEGF, an angiogenesis stimulator). In addition we measured the classical HIF target erythropoietin (EPO, a kidney-derived glycoprotein that stimulates erythropoiesis). Methods: Patients with OSA, an ODI > 15 and CPAP compliance of > 4 h/n for > 1 year from 3 RCTs were included. Patients were randomised to either two weeks of sham CPAP or continuing CPAP. Plasma ADM, EPO and serum VEGF levels were measured by ELISA at baseline and at two weeks, and differences between groups were compared. Results: Patients in the two groups (sham n=51, CPAP n=52) were well matched for OSA severity, BMI and age. There was a significant decrease in plasma ADM level at two weeks in the sham CPAP group compared to CPAP (-32.4pg/ml, p=0.009). There were no significant differences between the groups for VEGF or EPO levels. Conclusions: Unexpectedly, the return of OSA led to reductions in ADM, and no changes in VEGF or EPO levels, all of which are increased by sustained hypoxia. This suggests that the particular pattern of IH in OSA does not have the same effects as sustained hypoxia, and that the vascular effects occurring in OSA, could be brought about by mechanisms other than hypoxia, perhaps through a reduction in the vasodilator ADM.

Purpose The pressures delivered by autotitrating continuous positive airways pressure (CPAP) devices not only treat obstructive sleep apnoea (OSA) effectively but also give potentially interesting physiological information about the forces impinging on the pharynx. In earlier work from this unit, we used correlations between autoCPAP pressure and both OSA severity and obesity, to construct an algorithm to estimate the fixed CPAP pressure a patient required for subsequent clinical use. We wished to discover if these relationships could be reliably extended to a much more obese group. Methods We performed a prospective cohort study in an obese population. Measurements of obesity were made, OSA severity was recorded, and the 95th centile autoCPAP pressure was recorded during 1 week of autoCPAP. Spearman’s rank correlation was performed between measurements of obesity and autoCPAP pressure, and between OSA severity and autoCPAP pressure. Results Fifty-four obese individuals (median body mass index (BMI) 43.0 kg/m2), 52 % of whom had OSA (apnoea-hypopnoea index (AHI) ≥ 15), had a median 95th centile autoCPAP pressure of 11.8 cmH2O. We found no significant correlation between autoCPAP pressure and neck circumference, waist circumference or BMI. There was a moderate correlation between autoCPAP pressure and OSA severity (AHI r = 0.34, p = 0.02; oxygen desaturation index (ODI) r = 0.48, p Conclusions In this population, neither BMI nor neck circumference nor waist circumference is predictive of autoCPAP pressure. Therefore, the previously derived algorithm does not adequately predict the fixed CPAP pressure for subsequent clinical use in these obese individuals. In addition, some subjects without OSA generated high autoCPAP pressures, and thus, the correlation between OSA severity and autoCPAP pressure was only moderate.

Introduction Positional treatments have a long history of usage in obstructive sleep apnoea (OSA). Recent developments of more sophisticated therapies reported good response in patients with an AHI of 1,2 We hypothesised that patients with mild to moderate OSA usually have periods both with and without OSA, and that the OSA periods will be mainly due to supine OSA. Such patients might therefore be trialled on positional therapies without specific assessment of posture. Methods Patients included had OSA and underwent an in-hospital respiratory sleep study between May- July 2016. Sleep studies included video review for identification of supine sleep. The oxygen desaturation index >4% (ODI) was recorded in supine and non-supine positions. The ratio of the total to non-supine ODI was calculated. Results 40 patients’ sleep studies were suitable for analysis. 7 patients were excluded: 3 due to comorbidities (hypoventilation/CSA), 3 due to lack of supine sleep ( 2 (SD 9.0). The median supine ODI was significantly higher than the median total ODI (supine ODI 54.3/h, IQR 47.9; total ODI 28.6/h, IQR 34.4; p Discussion Our data suggests that patients with lower ODIs are more likely to have supine predominant OSA. At ODI values over 40 it is very unlikely that there is a posturally dependant component to a patient’s OSA. However, the reverse is not the case; although many patients with low ODIs do have a postural component, many do not. It is therefore necessary to objectively assess the degree of supine predominant OSA in future trials of positional therapies, but patients with ODIs over 40 could be excluded at the outset. References Levendowski DJ, et al . Assessment of a neck-based treatment and monitoring device for positional obstructive sleep apnea. J Clin Sleep Med 2014; 10 (8):863–71. Levendowski DJ, et al . Capability of a neck worn device to measure sleep/wake, airway position, and differentiate benign snoring from obstructive sleep apnea. J Clin Monit Comput 2015; 29 :53–64.

Introduction: Patterns of CPAP usage have been shown to be determined early. Early identification is important because patients with lower usage benefit less from CPAP. We wished to see if early CPAP usage was also predictive of longer term usage in minimally symptomatic patients. Methods: The MOSAIC trial was an international multicentre trial where patients were randomised to CPAP or standard care. Patients with OSA were recruited with an oxygen desaturation index 4% >7.5/ hour, but insufficient symptoms to mandate CPAP. Primary outcomes have been reported previously. CPAP usage data was downloaded at 2-4 week assessment and the week prior to 6 month assessment. Those who withdrew prior to 6 months were assumed to have 0h/n usage. Results: 195 patients were randomised to CPAP and 188 of these attended 2-4 week follow up with a median average usage of 2:49 h/n (interquartile range IQR 0:44,5:13). The median average usage at 6 months was 2:12 h/n (IQR 0:00,5:27). Average usage of CPAP at 2-4 week assessment was correlated with the average usage preceding 6 month assessment ([Figure 1][1]). [Figure 1][1]: Correlation between 2-4 week CPAP usage (h/ n) and the 6 month CPAP usage (h/ n). R=0.66, p

Introduction: It has been suggested that modifying the OSLER test (non-EEG-based behavioural maintenance of wakefulness test, MWT) improves its performance (1,2). We have tested whether modifying the original OSLER test improves its sensitivity in minimally symptomatic patients. Methods: The MOSAIC trial compared 6 months CPAP with standard care in 391 OSA patients with an oxygen desaturation index > 7.5 events/ hour whose symptom severity did not mandate CPAP treatment. The original OSLER test terminates when the subject fails to respond to 7 consecutive regular 3 second light flashes, or terminates at 40 minutes. It was performed at baseline and 6 months and showed significant improvements in the CPAP group. We reanalysed looking at time to 6, 5, and 4 consecutive misses, error rate and number of misses from 3-6, and assessed whether these new derivatives were better at distinguishing between the two groups. Results: OSLER tests were available for re-analysis in 118 standard care and 116 CPAP patients. Conclusions: None of the alternative analyses greatly improved the OSLER test9s ability to distinguish between patients on CPAP versus controls, in minimally symptomatic OSA. This contrasts with studies on more symptomatic OSA patients, either compared with healthy controls, or before and after treatment. 1) Mazza et al. AJRCCM 2002 166:474-8 2) Alakuijala et al. J Clin Sleep Med 2014 15;10:1075-82.

Background Anaesthesia worsens OSA, and may lead to respiratory and cardiac complications. Three critical incidents have occurred in the Oxford Hospitals in recent years. OSA is very common at around 5–25%, but half the cases are not diagnosed. So should we screen for OSA pre-operatively? Audit Over 9 months from July 2015 all patients completed a STOP-BANG questionnaire in a gynaecology pre-operative clinic. Those with snoring and a score of 3 or greater were referred for a sleep study. Data is presented for 102 patients (100 female; 2 transgender) with a mean ± SD age of 55.7 ± 11.4 yrs, BMI 35.8 ± 7.6 kg/m2 and collar size 40.0 ± 4.8 cm. The rate of non-attendance was high at 19/102 (19%), with those with a lower STOP-BANG score being more likely not to attend. Of those undergoing a sleep study, a new diagnosis was made in 53/83 (52%) patients. Symptoms and OSA/hypoventilation were sufficient for CPAP to be started in 23 patients and NIV in 1 (29% of those screened), with positive diagnoses more likely with higher STOP-BANG scores. The median (IQR) time to CPAP set-up was 80 (52, 100) days, thus a substantial proportion of patients had surgery before treatment. How should we ensure anaesthetic safety for patients at risk of OSA? Completing a sleep study and establishing OSA patients on CPAP prior to surgery would significantly slow the surgical pathway, and there is no evidence that this would improve outcome. However it seems sensible for anaesthesia of all patients deemed at risk of OSA (STOP-BANG 3+) to be managed with special precautions. We pragmatically recommend that all patients found to have a STOP-BANG score of 5+ or strong clinical suspicion of OSA, who are undergoing major surgery AND in whom it is reasonable to delay surgery, are referred for a sleep study prior to surgery. Patients with a STOP-BANG of 3+ not falling into this category should be informed they are at risk of OSA, and advised to seek a referral from their GP to the sleep clinic if they find symptoms of sleepiness troublesome.

Introduction Severity of OSA and early patterns of CPAP usage have previously been shown to determine subsequent long term CPAP use in patients with symptomatic moderate-to-severe disease. 1 We wished to see if different factors influenced compliance in minimally symptomatic patients. Methods Patients were randomised to 6-months of CPAP or standard care if they had an ODI of >7.5 h due to OSA on a baseline sleep study, but had insufficient daytime OSA symptoms to mandate CPAP. 2 Baseline characteristics (Table 1), medical history, ESS, SAQLI and SF-36 were recorded. Repeat overnight pulse oximetry was performed after entry for uniformity of trial ODI across recruiting centres. CPAP usage data were downloaded at the 2–4 week assessment, and at the 6 month assessment. Those who withdrew were assumed to have 0:00 h/n usage. Correlations were calculated between CPAP usage at the 6 month assessment and both the baseline characteristics and to the 2–4 week CPAP usage data. Results Median CPAP usage at 2–4 week follow-up was low at 2:49 h/n (n = 174, IQR 0:44, 5:13). Median usage at 6 month follow-up was 2:17 h/n (n = 195, IQR 0:08, 4:54). At 6 months males had significantly greater mean usage at 2:56 h/n compared to 1:47 h/n in females (95% confidence intervals of the difference, -1:49 to -0:09 h/n, p = 0.02). There were no other significant predictors of 6 month usage (age, BMI, ODI, ESS, sleep symptoms, smoking status, ethnicity, SAQLI, SF-36). Average usage of CPAP at 2–4 week assessment was moderately correlated with the average usage at the 6 month assessment (r = 0.76, p Conclusions Male gender predicted greater CPAP usage at 6 months, but no other baseline characteristics were predictive of CPAP usage in these minimally symptomatic patients with generally mild OSA. 2–4 week CPAP usage was predictive of 6 month usage, but by no means could all patients’ usage be predicted at such an early stage. Thus in clinical practice, trials of CPAP are necessary in patients with minimally symptomatic OSA but it may be necessary for patients to try CPAP for longer than one month to determine those benefitting from treatment in the long term. References 1 Thorax 2010; 65 :829–32 2 Thorax 2012; 67 :1090-66

The Multicentre Obstructive Sleep Apnoea Intervention Cardiovascular (MOSAIC) trial investigated the effect of continuous positive airway pressure (CPAP) on both sleepiness and predicted cardiovascular risk over 6 months in minimally symptomatic patients with obstructive sleep apnoea. Although there was clear benefit in terms of Epworth Sleepiness Score, there was no improvement in blood pressure and predicted vascular risk score. In order to calculate the required size of future trials, with real vascular events as the endpoint, the rate of such events in this population is needed. 188 patients from the original trial were followed for 2 years. The overall number of new vascular events over the 2 years was 25, and all-cause mortality was 4. There was a weak statistically significant reduction in vascular events in the CPAP group (p=0.049). Large-scale randomised trials are needed to determine if CPAP causes a real reduction in vascular events in minimally symptomatic patients. Based on our figures, future trials of CPAP versus no treatment would need to randomise approximately 2540 patients to not miss a real reduction in vascular events and over 6000 for mortality.

Introduction The MOSAIC multicentre trial investigated the effect of CPAP versus no CPAP on both sleepiness and a vascular risk score, over 6 months, in nearly 400 minimally symptomatic patients with OSA. The results on the vascular risk score, reported previously, suggested no potential vascular benefit of CPAP, although endothelial function improved. The incidence of real events is needed to calculate the size of any future trials in this group of patients. Methods We have followed the Oxford cohort of 189 patients for two years to assess real vascular event rates and the incidence of accidents and hospital admissions. The events have been verified by inspection of hospital notes and phone calls to patients. The CPAP/No CPAP allocation was based on intention to treat. At the end of the original 6 month trial, 71% of patients, initially randomised to CPAP, stated an intention to continue CPAP. Results The table shows the 2 year incidence of accidents at home, work and driving (66/189), the incidence of new vascular events (25/189), and all cause mortality (4/189). Conclusions The event rates are moderate, and there is no statistically significant difference between the groups. A power calculation, based on these figures, suggests that in order not to miss a 30% reduction in relative risk over 2 years (4% absolute reduction), with 90% power, would require 2,540 patients randomised; for accidents, 880; for mortality over 6,000.

Urinary isoprostanes, a key biomarker of oxidative stress, are not increased by OSA during CPAP withdrawal http://ow.ly/grU8305ZX1s