Role of hypoxia in inflammatory upper airway disease

Hypoxia is a potent stimulus for inflammation and remodeling. Hypoxia develops in chronic sinusitis as shown via tissue oxygen concentrations and colonization with obligate anaerobes. This hypoxia reflects occlusion of the sinus ostia and thereby failure of transepithelial oxygenation, nonvascularized exudates, and the tendency of inflammatory hyperplasia to exceed neovascularization.

Hypoxia-induced transcription factors are responsible for transcription of numerous inflammatory cytokines and growth factors, including vascular endothelial growth factor, CXCL8, CCL11, transforming growth factor-beta, inducible nitric oxide synthase, as well as matrix remodeling proteins such as procollagen and matrix metalloproteinases.

Many diseases, such as asthma, share the tendency to afflict respiratory epithelium of the lower (bronchi) and upper (sinus) airway. Although the histopathology and inflammation of asthma and its associated sinusitis share many features, aggressive fibrosis, polyp formation and intense hyperplasia are not features of asthma, a disease seldom associated with significant chronic hypoxia. In contrast, fibrosis is a cardinal feature of hypoxic diseases of the lungs such as interstitial lung diseases and primary pulmonary hypertension. Arguably, chronic sinusitis can be viewed as reflecting both 'asthma' and 'primary pulmonary hypertension' of the upper airway.