Chronic obstructive pulmonary disease is a common chronic lung disease affecting more than 10% of Canadians. Patients with COPD have significant morbidity from the disease as almost 60% of Albertans living with COPD were hospitalized between 2012-2014. Sleep related breathing disorders (SRBD) are a common comorbidity of COPD, and contribute to the morbidity associated with COPD. The most common SRBD is OSA. It is estimated that 1.0-3.6% of Canadians are affected by both OSA and COPD. People with COPD and OSA have lower sleep quality, lower oxygen saturations and greater nocturnal oxygen desaturations when their sleep is compared to people with OSA. Observational studies suggest that patients with OSA and COPD have a higher risk of hospitalization, exacerbation of COPD, or death; however, the evidence to support the assessment and management of OSA improving COPD health outcomes has not been considered substantial enough to justify inclusion in COPD guidelines. Other SRBDs that may impact patients with COPD are sleep-related hypoventilation as a consequence of obesity, or central sleep apnea as a consequence of cardiac disease, stroke or use of opioids; however, these are less common and less studied types of SRBD within sleep literature.
Two treatments that are commonly prescribed for SRBD are CPAP or NIV. In patients with OSA, CPAP improves quality of life, daytime sleepiness, and blood pressure control. In patients with COPD who have OSA, observational studies suggest that CPAP use is associated with survival, with the duration of CPAP use per night lowering mortality in a dose dependent manner, an increased time to first moderate-severe COPD exacerbation and fewer hospitalizations related to exacerbations of COPD. The association of decreased health care utilization with CPAP is greater in patients with a higher COPD complexity and number of comorbidities, indicating those who are the sickest may derive the most harm from untreated disease. NIV is better tolerated than CPAP in some patients with OSA; yet, there have been only a few studies evaluating its use for a SRBD in COPD. Further work in this area is critically important as the indications for use of NIV are expanding among patients with COPD.
We are uniquely positioned to complete this study as NIV is provided province-wide in Alberta and patient health outcomes are available in provincial databases. In addition, within the provincial titration protocol for polysomnography, NIV is provided preferentially over CPAP with oxygen, differentiating the management of these patients from the titration protocols used in other studies.
Through this study, we will explore whether treatment with NIV or CPAP for a SRBD in patients with COPD results in fewer moderate-severe exacerbations of COPD and whether the use of these devices have an impact on health care utilization and mortality. In a subgroup analysis, we will explore whether NIV use results in similar outcomes as CPAP, and account for differences in disease severity in this comparison. Adherence with these CPAP or NIV will also be summarized. The results from this study will inform regional care as well as provide insight into the roles of CPAP and NIV in the treatment of SRBD in patients with COPD.
Sample size:
59% of Albertans with COPD experience an exacerbation within a 2 year period; however, a conservative estimate of 50% will be used for the power calculation. A clinically significant difference in COPD exacerbations is estimated to be 25%. An estimated standard deviation of 8 patients hospitalized per 2 years was estimated (variance 64). Given that the exposure group will be stratified by use of CPAP or NIV in subgroup analysis, a 2:1 proportion for the exposure to comparison group was utilized and the exposure arm will be composed of equal proportions of patients prescribed CPAP or NIV. A 10% drop out rate is anticipated.
Primary hypothesis: Null hypothesis (H0): CPAP or NIV is equivalent to no therapy; Alternate hypothesis (H1): CPAP or NIV is better than no therapy
Secondary hypothesis: Null hypothesis (H0): NIV is equivalent to CPAP; Alternate hypothesis (H1): NIV is better than CPAP
For the primary hypothesis, these estimates suggest that a sample size of 165 patients is required (n=110 patients in the exposure arm and 55 patients in the control arm). For the secondary hypothesis, it is not anticipated that a large difference between CPAP or NIV will be observed; however, the subgroup analysis of the primary outcome will be powered to detect a 25% difference between intervention with CPAP or NIV.
