Non-invasive study of airways inflammation in sleep apnea patients

Summary

The current view foresees that airway inflammation and oxidative stress are both important in the pathophysiology of obstructive sleep apnea syndrome (OSAS). Notwithstanding the fact that these events play a key role in OSAS, their monitoring is not included in the current management of this disease.

The direct sampling of airways is made possible today thanks to what can be defined as quite invasive techniques, such as bronchoscopy with broncho-lavage and biopsy. Recently there has been increasing interest in the non-invasive methods that allow the study of airways via the induced sputum (IS), the exhaled breath volatile mediators and the exhaled breath condensate (EBC). The non-invasiveness of these techniques makes them suitable for the evaluation and serial monitoring of OSAS patients. The aim of this review is to spread current knowledge on the non-invasive airway markers and on their potential clinical applications in OSAS.

Introduction

It is currently estimated that 5–10% of adults in Europe manifest some degree of obstructive sleep apnea syndrome (OSAS)¹ and that the economic burden for OSAS cases not coming to medical attention is steadily increasing,² thus making OSAS a major public health concern. In the light of its increasing incidence amongst the general population, the interest of researchers and clinicians has been recently directed to the study of pathological mechanisms underlying sleep disorders. Current opinion has it that airway inflammation and oxidative stress are both important in the pathophysiology of OSAS and its comorbidity. These key events seem to be the consequence of the local, repeated mechanical trauma related to the intermittent airway occlusion typical of the disease. Another potential mechanism involved is intermittent nocturnal hypoxemia which, through the phenomenon of ischemia-reperfusion injury, may induce the production of oxygen-free radicals and therefore cause local and systemic inflammation. Finally, a state of low-grade systemic inflammation may be related to obesity per se with the pro-inflammatory mediators synthesized in the visceral adipose cells.

Airway inflammation is closely linked with systemic inflammation, something which is known to play a fundamental role in the pathogenesis of arteriosclerosis and endothelial dysfunction.³ As a consequence, local inflammation seems to contribute to increasing cardiovascular diseases in OSA patients.³

However, the relationship between local and systemic inflammation still remains poorly understood. In this context two different hypotheses may usefully be evaluated: the first and easier hypothesis could well be that local inflammation is a direct consequence of systemic inflammation. Thus all the mechanisms involved in the development of systemic inflammation – such as intermittent hypoxia, sympathetic activation, obesity, sleep fragmentation, and the like – seem to be at the same time responsible for airway inflammation. On the contrary, another hypothesis suggests that airway inflammation is linked with the local injury consequent to mechanical stress, airway fat deposition or presence of comorbidity such as gastroesophageal reflux (Fig. 1). Obviously, both theories can co-exist; indeed, this is likely to be the better explanation.

To carry out an in-depth study of the inflammation can help us to understand more details about this relationship. However, the monitoring of inflammation is still not included in the current management of the OSAS.

The direct sampling of airway cells and mediators can be achieved by using what can be defined as quite invasive techniques, such as bronchoscopy with broncho-lavage and biopsy. However, these collection methods are not always well accepted by patients, as well as being not repeatable, and are therefore not suitable for clinical monitoring.

Recently there has been increasing interest in the investigation of lungs by non-invasive means measuring the inflammatory cells in the induced sputum (IS), the exhaled breath volatile mediators, such as nitric oxide (NO), carbon monoxide (CO), ethane and pentane, and finally the non-volatile substances in the liquid phase of exhalate (e.g., hydrogen peroxide), termed breath condensate. The non-invasiveness of these techniques for the study of airways affected by different respiratory disorders and among those, the OSAS, makes these ideally suited for the evaluation and serial monitoring of patients.

This review describes the current knowledge on airway inflammation and oxidative stress in OSAS assessed by non-invasive methods such as exhaled breath condensate (EBC) and IS, as well as discussing the advantages, the limitations, and the potential clinical applications of these techniques.