Similar relationships have been identified among other allergic and nonallergic respiratory diseases. Anecdotal associations between asthma and rhinosinusitis have been reported for more than 70 years.5 The prevalence of asthma, for instance, in patients with chronic rhinosinusitis (approximately 20%) is consistently noted to be much greater than that observed in the general population (5-8%),6 and in those patients who undergo endoscopic sinus surgery the prevalence climbs even higher, to approximately 42%.7 This same association exists between chronic rhinitis and allergic rhinitis, as shown by a cohort of patients with the diagnosis of recurrent acute or chronic rhinosinusitis who were followed within a major health care system. In this study, patients diagnosed with chronic rhinosinusitis demonstrated a 57% prevalence of positive in vitro or allergy skin testing.8
Explore this issue:August 2007
The overlap and interrelationship of these respiratory diseases become less surprising as definitions of disease and underlying pathophysiologies come into better focus. The concept of asthma as a chronic inflammatory disease emerged in 1991 as a result of a report by the National Institute of Health and the National Heart, Lung, and Blood Institute.9 With this report, the pathophysiological focus of asthma shifted from bronchospasm to one of inflammation that is mediated at the cellular level. The implications of this report were monumental and resulted in a major shift in treatment strategy for the disease. It was not until later that similar observations resulted in refinements in the definition of chronic rhinosinusitis. In 2003, a definition of chronic rhinosinusitis was introduced that emphasized the pathogenic role of inflammation in the disease.10
Inflammation as a common theme underlying the definitions of both chronic upper and lower respiratory disease makes sense for several reasons. The respiratory epithelium that lines the nose, sinuses, and lower airways is composed of the same pseudostratified, ciliated, columnar epithelium. Functionally, these respiratory surfaces share many similarities. In the case of chronic inflammation, mucosa of upper and lower air passages demonstrate similar patterns of inflammatory cellular infiltrate and eventual basement membrane thickening.11 Histopathology consistently points to the eosinophil as the primary effector cell common to all these diseases. Eosinophilic inflammation, thought originally to represent evidence of allergic stimulation, is now recognized as important to Th2-mediated inflammation independent of allergy. Other common inflammatory cells include CD4 T-lymphocytes and other mononuclear cells.1
Perhaps even more intriguing evidence of the overlap and potential interplay of asthma, allergy, and rhinosinusitis are commonalities in cytokines expressed by CD4 lymphocytes within inflamed respiratory tissue and the resulting cascade of local and regional events. Lemanske and Busse12 described cytokines released from patients with asthma. Cytokines such as interleukin (IL)-4, IL-5, and IL-13 are produced by Th2 lymphocytes in conjunction with chemokines such as RANTES and eostaxin. This soup of mediators leads to activation of cellular adhesion molecules, ICAM-1 and VCAM-1, essential for chemotaxis and activation of eosinophils to the site of inflammation. Evidence suggests that this signaling is not confined to one compartment of the respiratory tract. Inflammatory triggers from any one of these respiratory diseases appears capable of initiating inflammation at distant sites within the respiratory system. In fact, this characteristic of the unified airway theory is referred to as the concept of systemic amplification.