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Role of hypoxia in inflammatory upper airway disease

Steinke, John W; Woodard, Charles R; Borish, Larry

Current Opinion in Allergy and Clinical Immunology: February 2008 - Volume 8 - Issue 1 - p 16–20
doi: 10.1097/ACI.0b013e3282f3f488
Upper airway disease: Edited by Ruby Pawankar and David P. Skoner
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Purpose of review 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.

Recent findings 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-ß, inducible nitric oxide synthase, as well as matrix remodeling proteins such as procollagen and matrix metalloproteinases.

Summary 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.

aAsthma and Allergic Disease Center, Beirne Carter Center for Immunology, Department of Medicine, USA

bDepartment of Otolaryngology–Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, USA

Correspondence to Larry Borish, Asthma and Allergic Disease Center, Box 801355, University of Virginia Health System, Charlottesville, VA 22908, USA Tel: +1 434 243 6570; fax: +1 434 924 5779; e-mail: lb4m@virginia.edu

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