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4 to 6 weeks. Although data from these studies support the use in itraconazole as an adjuvant therapy in select patients with CRS, larger prospective trials are needed to develop guidelines for dose and duration and to determine which patients would benefit most from therapy. OTHER TREATMENTS Decongestants There are no randomized clinical trials evaluating decongestant use for CRS. Decongestants are a-adrenergic agonists that induce the release of norepinephrine from sympathetic nerves leading to vasoconstriction of the nasal vasculature (5). They are used for relief of nasal congestion, but no studies have demonstrated quicker resolution of sinusitis. Symptoms are improved with topical decongestants, but reduced mucosal blood flow may increase inflammation (70) and increase ciliary loss (71). Despite these reservations, topical decongestants will usually reduce symptoms and speed recovery in patients with rhinosinusitis. However, topical decongestants, such as oxymetazoline or Neo-Synephrine, should not be used for longer than 3 days to avoid rebound nasal congestion and rhinitis medicamentosa. Mucolytics Mechanical drainage can also be improved with a mucolytic. Guaifenesin is the most commonly used medication to thin mucus secretions. In a double-blind study involving HIVpositive patients, Wawrose and colleagues (72) reported less nasal congestion and thinner postnasal drainage at doses of 2,400 mg/d at 3 weeks. Nausea was the major reported side effect in doses greater than 1,200 mg/d. Antihistamines Antihistamines work by competitive inhibition of histamine receptor sites on respiratory mucosal cells. Histamine type 1 blockers are most effective for atopic patients with symptoms of watery rhinorrhea, sneezing, and facial itching (5, 8). Antihistamines are first-line therapy for allergic rhinitis (73). Secondgeneration antihistamines have a higher affinity for the histamine receptor, with less of the sedating anticholinergic effects. Azelastine, a topical nasal second-generation antihistamine, has also demonstrated antiinflammatory and mast cell–stabilizing properties (74, 75). The anticholinergic effects of the first-generation antihistamines can cause excessive drying, which can impair mucus clearance by thickening mucus. At this time, there is no evidence to 136 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 8 2011 support the use of antihistamines for treatment of patients with acute bacterial rhinosinusitis or chronic rhinosinusitis (5). Leukotriene Inhibitors Leukotriene inhibitors are systemic medications that are used for the treatment of asthma and allergic rhinitis. The drugs block leukotrienes that cause contraction of smooth muscle, chemotaxis, and increased vascular permeability (5, 8). The observation that leukotriene levels are increased in the nasal secretions of people with asthma with aspirin sensitivity and nasal polyposis raised the possibility that antileukotriene therapy could benefit patients with CRS with nasal polyps (8). Some studies have demonstrated some effect on reducing sinonasal symptoms and nasal polyps (76). Jung and colleagues (77) demonstrated increased leukotrienes as well as other arachidonic acid metabolites in nasal polyps from patients with aspirin sensitivity, nasal polyposis, and asthma. At this time, more research is required to determine which subset of patients with CRS will benefit most from leukotriene inhibitors. SURGICAL TREATMENT OF CRS In general, the incidence of patients with CRS requiring surgery is very low, and surgery is reserved for patients who fail medical management. However, in selected patient populations, up to 50% of patients with CRS (not acute sinusitis) will ultimately require surgical intervention (78). The most common reasons for surgical intervention are CRS that does not respond to
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