Obstructive Sleep Apnoea and COPD: Can we use auto-titrating ventilator devices? Dr. Patrick B. Murphy Lane Fox Unit, Guy s & St Thomas Hospital Westminster Bridge Rd SE1 7EH London UNITED KINGDOM patrick.murphy@gstt.nhs.uk AIMS Describe epidemiology of COPD-OSA overlap syndrome Outline the pathophysiology of sleep disordered breathing in COPD-OSA overlap syndrome Assess need for therapeutic intervention Rationale for auto-titrating modes and potential benefits SUMMARY Introduction Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are 2 of the most prevalent respiratory conditions in the western world. As such they would be frequently expected to co-exist, and estimates based on population prevalence data suggests that approximately 1% of the general population could be affected, compared to estimates of 0.3% for obesity hypoventilation syndrome.[1, 2] Furthermore, there are features of COPD, such as cigarette smoking, steroid associated weight gain and nocturnal rostral fluid shift, which may increase the likelihood of OSA. Increasing rates of obesity within the general population and specifically within patients with COPD is likely to further increase prevalence of the overlap syndrome making it pertinent that the clinician is aware of the clinical features and optimal management.[3] Pathophysiology Nocturnal symptoms are common in COPD and significantly impact on patient quality of life and function which is frequently underestimated by physicians.[4] Patients with COPD have increased objective sleep latency and sleep fragmentation with subsequent impact on subjective sleep quality.[5] The impact of the normal physiological changes which occur during sleep are magnified in patients with COPD-OSA overlap leading to significant hypoxia, hypercapnia and further sleep fragmentation.[6, 7] Patients with COPD-OSA have significantly worse sleep quality compared to patients with either COPD or OSA alone.[7] Although bronchodilators used to treat COPD have been shown to improve nocturnal hypoxia they do not significantly improve sleep architecture.[8, 9] Although continuous positive airway pressure (CPAP) can act as a pneumatic splint for the upper airway this can adversely affect pulmonary mechanics in patients with COPD, exacerbating hyperinflation. This has the potential to exacerbate sleep fragmentation as degree of hyperinflation in COPD correlates with sleep efficiency. Furthermore application of high levels of CPAP during the day has been shown to exacerbate breathlessness in patients with OSA and correlates with
subsequent CPAP compliance, a similar relationship between breathlessness on PAP has been demonstrated in COPD-OSA overlap.[10] Clinical consequences Despite its prevalence COPD-OSA overlap may go unrecognised due to the high levels of nocturnal symptoms in COPD alone and the poor predictive value of commonly used tests such as the Epworth sleepiness score.[11] COPD-OSA overlap syndrome has a range of clinical consequences for patients outside of the expected sequelae of sleep disruption and daytime hypersomnolence. There is compelling evidence that exacerbation frequency is higher in patients with overlap syndrome with the inevitable impact on health status and disease progression.[12-14] The hypoxic load associated with sleep disordered breathing also appears to increase the inflammatory pathway and lead to adverse cardiovascular consequences and increased rates of arrhythmias.[15, 16] The complex interaction between the inflammatory pathways which are part of the pathological process of atherosclerotic plaque formation leading to ischaemic heart disease and overlap syndrome are yet to be fully elucidated. In addition to the impact on disease severity and health related quality of life patients with COPD-OSA have a higher mortality than patients with COPD alone with particular burden at night during acute exacerbations.[14, 17] Treatment All patients with overlap syndrome should have optimisation of medical management for COPD performed including pulmonary rehabilitation as well as pharmacotherapy. However, the impact of these interventions on sleep quality is limited.[8, 9, 18] Treatment of the OSA element of overlap syndrome with CPAP therapy improves sleep architecture and reduces respiratory events. This has the effect of improving daytime symptoms and there is a suggestion of reduced exacerbations and improved mortality.[14] Data supporting the impact of CPAP on mortality are based on non-randomised trials using non-compliant or not treated patients as controls, with significant numbers of non-compliant patients. Detailed assessment of outcomes suggests that the benefit of CPAP therapy on mortality may be confined to those patients with significant hypercapnia.[19] The large numbers that are non-compliant with therapy raise several important questions. Firstly, this may bias the results of the reported studies with non-compliant patients making other poor health choices that mean they serve as poor quality controls and may therefore over estimate any treatment effect. The poor level of complaince may be attributable to adverse effects of therapy. The level of CPAP required to maintain airway patency varies through sleep stages and body position and is set at the minimum level which achieves this throughout the night during a manual titration or 95 th centile from an auto-titration study. This means that the delivered fixed level CPAP is often substantially higher at sleep onset than is required to open the airway. The fixed pressure is delivered to the lower airway and can exacerbate the static hyperinflation associated with COPD. Worsening hyperinflation works to worsen dyspnoea and may negatively impact on sleep quality therefore reduce patient compliance with CPAP.[20] Data from both OSA and COPD-OSA suggest that reported breathlessness when on PAP during wakefulness correlates to future device compliance with the most breathless patients having the worst compliance.[10] The use of an auto-titrating device is therefore of empirical appeal with only the necessary level of CPAP applied at any given time point preventing unnecessary exacerbation of hyperinflation.
Auto-titrating devices The most recent American Academy of Sleep Medicine practice parameters recommends not using auto-titrating devices in COPD-OSA overlap due to a lack of data on clinical efficacy [21]. The majority of auto-titrating CPAP devices use flow wave analysis to examine for flow limitation and optimisation of upper airway patency. Flow wave analysis is more difficult in patients with COPD due to changes in flow characteristics and as such general algorithms may be less successful in identifying flow limitation. Newer devices have been developed which use forced oscillatory technology to assess upper airway patency which overcomes some of the difficulties of flow wave analysis. There are limited data to guide the clinician on the efficacy of such modes but a small pilot study has demonstrated that one such mode, AVAPS-AE (Philips-Respironics, Murrysville, Pa, USA), can stabalise complex sleep disordered breathing in COPD-OSA and may enhance patient comfort and compliance.[22] The pilot study took 10 patients established on fixed bilevel non-invasive ventilation (NIV) for COPD-OSA and in a sequential non-randomised trial transferred them to AVAPS-AE with single night polysomnography (PSG) and follow up limited respiratory polygraphy on night 14 and 42. The 1 st night PSG demonstrated safe and effective control of sleep disordered breathing which was maintained over the following 6 weeks whilst using the novel ventilator. Arterial blood gas analysis and diary card review confirmed clinical stability over the trial period. Interestingly there was improved reported sleep comfort associated with increased ventilator compliance over the trial (Δ126 min, 95%CI 9 to 243 min, p=0.035). The ventilator download indicated a trend to lower EPAP and higher pressure support over the trial period when compared to fixed bilevel pressures supporting the concept that reduced hyperinflation achieved by reducing applied PAP led to benefits in breathlessness, sleep quality and thus compliance. Conclusion COPD-OSA is a prevalent condition that is associated with worse outcomes than the individual diseases alone. Treatment in symptomatically sleepy patients is mandatory but other benefits such as reduced exacerbation frequency need to be confirmed in non-sleepy patients in well conducted randomised controlled trials. Algorithms used to assess upper airway patency are largely based on flow wave analysis and have few data to support their use in overlap syndrome. Clinicians should use algorithms with data in this specific patient population, manual titration in order to obtain therapeutic PAP levels. REFERENCES 1. McNicholas WT. Chronic obstructive pulmonary disease and obstructive sleep apnoea-the overlap syndrome. J Thorac Dis 2016;8(2):236-42 doi: 10.3978/j.issn.2072-1439.2016.01.52 jtd- 08-02-236 [pii][published Online First: Epub 2. Mokhlesi B. Obesity hypoventilation syndrome: a state-of-the-art review. Respir Care 2010;55(10):1347-62; discussion 63-5 3. Marquis K, Maltais F, Duguay V, et al. The metabolic syndrome in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil 2005;25(4):226-32; discussion 33-4 doi: 00008483-200507000-00010 [pii][published Online First: Epub 4. Price D, Small M, Milligan G, Higgins V, Gil EG, Estruch J. Impact of night-time symptoms in COPD: a real-world study in five European countries. International journal of chronic obstructive pulmonary disease 2013;8:595-603 doi: 10.2147/COPD.S48570[published Online First: Epub
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