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Friday, December 4, 2015

Current and future treatment options for adult chronic rhinosinusitis: Focus on nasal polyposis

Chronic rhinosinusitis affects approximately 10% of the adult population in industrialized countries. Its effects range from pain in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) to nasal obstruction and comorbid asthma in those suffering from chronic rhinosinusitis with nasal polyps (CRSwNP). Current therapy approaches, such as pharmacotherapy and endoscopic surgery, focus on these two phenotypes. They have not, however, proved effective regarding long-term control of symptoms or risk of recurrence for many patients with severe polyp disease. Bachert et al. discuss the current shift in treatment focus from phenotype to endotype and the related innovative therapies on the horizon (J Allergy Clin Immunol 2015; 136(6): 1431-1440).

A clinical phenotype groups patients with similar clinically observable characteristics. Various pathomechanisms underlie a given phenotype. Understanding and characterizing disease via a shared and unique pathomechanism creates an endotype, opening novel targets for therapeutic intervention. Patients with severe CRSwNP, associated with disease recurrence and comorbid asthma, show TH2-biased inflammation and IgE formation. This has led to proof of concept studies using interventions such as Omalizumab, Reslizumab, Mepolizumab, and Dupilumab to target the associated TH2 cytokines. None of these has been registered yet for the indication of nasal polyposis, and it is unclear if one has advantages over the others.

For patients with severe CRSwNP, topical glucocorticosteroids are usually not effective. The permanent application of oral corticosteroids would lead to health deterioration, and repeated surgeries are not a feasible option. While biologics pose problems that remain to be solved, including the necessity of regular systemic application with the risk of side effects and the high financial cost, they offer a direction that is nonetheless promising. Approaches including silencing techniques, or the blocking of transcription factor GATA-3, and the local application of apathogenic bacteria to produce therapeutically effective proteins are currently under investigation as well.

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