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ObjectivesUnilateral clear thin rhinorrhea (UCTR) can be concerning for a nasal cerebrospinal fluid (CSF) leak. Beta‐2 transferrin electrophoresis has been the gold standard for initial non‐invasive confirmatory testing for CSF rhinorrhea, but there can be issues with fluid collection and testing errors. Ipratropium bromide nasal spray (IBNS) is highly effective at reducing rhinitis‐related rhinorrhea, and should presumably not resolve CSF rhinorrhea. This study assessed whether different clinical features and IBNS response helped predict presence or absence of CSF rhinorrhea.MethodsA prospective cohort study was conducted where all patients with UCTR had nasal fluid tested for beta‐2 transferrin, and were prescribed 0.06% IBNS. Patients were diagnosed with CSF rhinorrhea or other rhinologic conditions. Clinical variables like IBNS response (rhinorrhea reduction), positional worsening, salty taste, postoperative state, female gender, and body‐mass index were assessed for their ability to predict CSF rhinorrhea. Sensitivity, specificity, and predictive values and odds ratios were calculated for all clinical variables.ResultsTwenty patients had CSF rhinorrhea, and 53 had non‐CSF etiologies. Amongst clinical variables assessed for predicting CSF absence or presence, significant associations were shown for IBNS response (OR = 844.66, p = 0.001), positional rhinorrhea worsening (OR = 8.22, p = 0.049), and body‐mass index ≥30 (OR = 2.92, p = 0.048). IBNS response demonstrated 96% sensitivity and 100% specificity, and 100% positive and 91% negative predictive values for predicting CSF rhinorrhea.ConclusionsIn patients with UCTR, 0.06% IBNS response is an excellent screening tool for excluding CSF rhinorrhea, and should be considered in the diagnostic workup of CSF rhinorrhea.Level of Evidence2 Laryngoscope, 2023