Clinical reviewCurrent evidence on prevalence and clinical outcomes of co-morbid obstructive sleep apnea and chronic obstructive pulmonary disease: A systematic review
Introduction
Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are common respiratory diseases. The concurrent presence of these two conditions in one individual is referred to as the “overlap syndrome” [1], a term first introduced by D.C. Flenley [2]. COPD is characterized by airflow obstruction, which is not fully reversible [3]. Obstructive sleep apnea results from obstruction of upper airway during sleep and leads to periodic apneas and hypopneas causing reduction in blood oxygen saturation. This often leads to symptoms like loud snoring, awakening due to gasping and choking and daytime sleepiness [4], [5]. There is substantial variation in the reported prevalence estimates for overlap syndrome between epidemiological studies thus far. This is likely to relate to the use of differing definitions for both OSA and COPD, and different study populations. Although narrative reviews exist which have highlighted some of these limitations in the current evidence and outlined gaps in our knowledge [1], [6], the evidence has not been systematically reviewed and synthesized.
The simultaneous occurrence of COPD and OSA can lead to more pronounced nocturnal oxygen desaturation (NOD) than when either condition occurs in isolation, which subsequently may increase the risk of multiple comorbidities ∗[7], ∗[8]. OSA causes repetitive and transient oxygen desaturations that induce oxidative stress, autonomic dysfunction, systemic inflammation and endothelial dysfunction. These have been proposed as possible complex pathophysiological mechanisms for the development of cardiovascular disease among OSA patients [9], [10]. Additionally, COPD increases the risk of cardiovascular disease by increased sympathetic nervous activity and persistent low-grade systematic inflammation [11]. However, whether these effects are additive or synergistic in overlap syndrome patients is not yet established and there is no epidemiological evidence studying the possible interaction between these two disorders on the development of cardiovascular diseases.
COPD patients with co-existent OSA have been reported to have poorer health related quality of life (QoL), in part related to sleep disruption and worse nocturnal oxygen desaturation [12]. The presence of sleep apnea has been shown to increase the rate of COPD exacerbation, hospitalization and mortality when compared with COPD-only patients ∗[13], [14]. Given that co-existing COPD and OSA patients have increased healthcare utilization, this poses a significant economic burden on the health system [15] Therefore, early identification and timely treatment is imperative for reducing morbidity and mortality in patients with overlap syndrome.
To our knowledge, no systematic review to date has collated evidence on the prevalence and clinical outcomes of overlap syndrome. The objective of this systematic review is to synthesize the evidence from observational epidemiological studies and, subsequently, recommend future research directions in this field.
Section snippets
Methods
We conducted this systematic review by following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines [16].
Results
Our final PubMed search yielded 591 articles. We excluded 542 articles after preliminary screening of titles and abstracts against the eligibility criteria. After reviewing full texts of 49 articles, 27 articles were selected for inclusion (Fig. 1). All the studies were conducted on middle aged to elderly populations of participants aged from 40 to 90 y.
Prevalence of overlap syndrome
The included studies reported the prevalence of overlap syndrome in three groups i.e., samples taken from the general and hospital population, OSA patients and COPD patients. The studies that included samples from the general population and hospitals reported much lower prevalence of overlap syndrome than the studies that sampled patients with either OSA or COPD.
Polysomnographic findings in overlap syndrome patients
Eight studies reported the findings from polysomnography of overlap syndrome patients and compared them with OSA only patients ∗[7], [18], ∗[19], [26], [32], [33], ∗[34] (Table 4). There were no significant differences in AHI across the included studies. The oxygen desaturation measured by mean peripheral capillary oxygen saturation (SpO2) was significantly greater in overlap syndrome patients than OSA patients in most of the studies ∗[7], [18], [32], [33]. In overlap patients, total sleep time
Clinical outcomes in overlap syndrome patients
The included studies reported various types of clinical outcomes, including cardiovascular diseases, mortality, COPD exacerbation, quality of life, as well as utilization of medical resources and associated costs (Table 5). Overlap syndrome was associated with increased nocturnal oxygen desaturation leading to increased cardiovascular comorbidities, including significantly higher proportions of pulmonary hypertension ∗[7], [32]; a higher incidence of new-onset atrial fibrillation [21] and right
Discussion
From this systematic review, the major findings are: 1) overlap syndrome is not common in the general population (range 1–3.6%), but is highly prevalent when populations of either COPD or OSA are assessed (range: 2.9–65.9%); 2) overlap syndrome patients suffer from a greater degree of NOD (i.e., reduced mean SpO2 and increased sleep time spent with SpO2 < 90%) and worse sleep quality than patients with OSA alone; 3) compared to either condition alone, overlap syndrome is associated with more
Conclusion
This systematic review documents that even though COPD and OSA are individually quite common in the general population, their co-existence is not highly prevalent at a population level. However, overlap syndrome is much more common when considering populations diagnosed with either OSA or COPD. Unfortunately, current evidence is not sufficient to delineate the true association between these two diseases due to variations in study population, definition, and methodology. The overlap syndrome is
Conflicts of interest
The authors do not have any conflicts of interest to disclose.
Acknowledgments
No financial support was taken for conducting this systematic review. Associate Professor Garun Hamilton has received equipment for research from Resmed, Philips Respironics and Compumedics Ltd. None of the other authors declared a conflict of interest.
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