Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea: The overlap syndrome

Aggelos S. Aggelakas, MD
Medical Department, St. Anargiroi General Hospital

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Cite as: Aggelakas AS. Chronic Obstructive Pulmonary Disease and Sleep Apnea: The Overlap Syndrome. Alveolus 2013; 1(1):6-8

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) represent two of the most prevalent chronic respiratory disorders in clinical practice. The coexistence of OSA and COPD is also common, and is was described by Flenley in 1985 as the overlap syndrome[1]. Recent epidemiological data suggest that the two disorders coexist in approximately 1% of adults[2], while the overlap syndrome occurs in 10–20% of patients with OSA[3]. Subclinical form of overlap syndrome could be estimated as 4% in men based on a reported prevalence of 16.8% for GOLD 1(Global Obstructive Lung Disease stages) and 24% among men for an apnea/hypopnea index (AHI) of at least 5/h[2].

Patients with overlap syndrome develop more pronounced nocturnal oxygen desaturation and hypercapnia than COPD or OSA alone, which predisposes to pulmonary hypertension and right heart failure[4]. Bradley et al. studied 50 patients with OSA and found that about 10% had evidence of right-heart failure.5 The risk factors for development of right-heart failure were daytime hypoxemia - hypercapnia and a reduced FEV1[5,6]  Clinical trials, have also demonstrated that even those with severe OSA alone, tend not to develop marked pulmonary hypertension if they are free from other cardiopulmonary disease[7]. However, they have confirmed the presence of pulmonary hypertension in those with the coexistence of obstructive lung disease and daytime hypoxemia and hypercapnia[8]. Additionally, Hawrylkiewicz et al. observed that 86% of those with overlap syndrome had pulmonary hypertension, compared with 16% of those with OSA[9].

Mortality data for patients with the overlap syndrome have not been well studied until recently. OSA has been reported to increase mortality in patients with COPD. Marin et al. studied patients with COPD and patients with the overlap syndrome and after a median follow-up of over 9 years, proved that the all-cause mortality was higher in the overlap group (42.2%) than in the COPD-only group (24.2%)[10]. Even when adjusted for COPD severity, comorbid OSA remained a risk factor for death. Similarly, both the diagnosis of concomitant COPD and markers of COPD, such as a reduced FEV1 or smoking history, increase mortality in OSA patients[11] and Lavie et al. showed that COPD conferred a 7-fold risk of death in OSA patients[12].

The relationship between COPD and OSA is determined by several pathophysiological mechanisms[2]. In COPD, the promoting factors for upper airway obstruction include rostral shift of peripheral edema when supine, predisposing to upper airway edema[13] and cigarette smoking, resulting in local upper airway inflammation. Furthermore, corticosteroids promote truncal obesity (a common feature of OSA), which causes ventilatory disturbances by reducing chest wall compliance and respiratory muscle strength[14]. Meanwhile, COPD has direct sleep effects such as diminished sleep quality and oxygen desaturation, factors that are directly correlated to OSA[2].

There is also increasing evidence that both COPD and OSA have systemic consequences and the most important is the cardiovascular disease. The mechanisms that contribute to cardiovascular disease are interlinked and multifactorial. Both COPD and OSA cause systemic inflammation via various mediators (tumor necrosis factor alpha, interleukin-6, and interleukin-8), in addition to the oxidative stress they create. Inflammation and oxidative stress develop as a result of hypoxia and they cause endothelial dysfunction[15-17]. This, in turn, promotes atherosclerosis, the cornerstone of cardiovascular disease. Therefore, it seems likely that the overlap syndrome is associated with greater cardiovascular morbidity and mortality than each disorder alone, although detailed studies are required to prove this possibility.

As far as treatment of the overlap syndrome is concerned, it doesn’t differ from treatment of the constituent diseases. The goal of treatment is to maintain adequate oxygenation at all times and to prevent sleep-disordered breathing. CPAP remains the accepted standard treatment for OSA, and currently is the accepted standard for overlap syndrome[18]. Marin et al. showed that CPAP therapy in overlap patients is associated with improved survival and decreased hospitalization rate[10]. Moreover, Machado et al. examined the impact of OSA treatment with CPAP on the survival of hypoxemic COPD patients. The authors reported that CPAP therapy was associated with a higher survival in patients with moderate-to-severe OSA and hypoxemic COPD. The 5-year survival rate was 71% and 26% in the CPAP-treated and nontreated groups, respectively[19].

In conclusion, COPD and OSA are prevalent worldwide and their effect becomes even higher when these diseases coexist. The overlap syndrome is associated with worst pulmonary implications, systemic consequences, morbidity and mortality than these of either COPD or OSA alone.. However long-term follow-up clinical studies are needed to clarify the exact pathophysiological mechanisms and clinical consequences of overlap syndrome.

 

References:

[1] Flenley DC. Sleep in chronic obstructive lung disease. Clin Chest Med. 1985; 6(4):651–661.

[2] McNicholas WT. Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease. Am J Respir Crit Care Med 2009; 180:692–700.

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[13] Redolfi S, Yumino D, Ruttanaumpawan P, et al. Relationship between overnight rostral fluid shift and obstructive sleep apnea in nonobese men. Am J Respir Crit Care Med 2009; 179:241–246.

[14] Poulain M, Doucet M, Major GC, et al. The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies. Can Med Assoc J 2006; 174:1293–1299.

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[17] Fabbri LM, Luppi F, Beghe B, et al. Complex chronic comorbidities of COPD. Eur Respir J 2008; 31:204–212.

[18] Toraldo D, De Nuccio F, Nicolardi G. Fixed-pressure nCPAP in patients with obstructive sleep apnea (OSA) syndrome and chronic obstructive pulmonary disease (COPD): a 24-month follow-up study. Sleep Breath 2010; 14:115–123.

[19] Machado MCL, Vollmer WM, Togeiro SM, et al. CPAP and survival in moderate-to-severe obstructive sleep apnoea syndrome and hypoxaemic COPD. Eur Respir J 2010; 35:132–137.

 

Conflicts of Interest: None