Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction

Jake J. Lee, Andrew M. Peterson, Dorina Kallogjeri, Pawina Jiramongkolchai, Sara Kukuljan, John S. Schneider, Cristine N. Klatt-Cromwell, Andrew J. Drescher, Joseph D. Brunworth, Jay F. Piccirillo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Objective: To evaluate the efficacy and safety of intranasal theophylline saline irrigation on olfactory recovery in patients with post-viral olfactory dysfunction (PVOD). Methods: Between May 2019 and April 2020, we conducted a double-blinded, placebo-controlled randomized clinical trial of adults with 6–36 months of PVOD. Patients were randomized to nasal theophylline saline irrigation or placebo saline irrigation twice a day for 6 weeks. The primary outcome was the Global Rating of Smell Change. Secondary outcomes were changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). Results: Twenty-two patients (n = 12, theophylline; n = 10, placebo) completed the study. Slightly more patients in the theophylline group (33%) reported improved smell compared to the placebo group (30%, difference 3.3%, 95% CI -35.6% to 42.3%). The median differences in pre- and post-treatment UPSIT and QOD-NS change between the two groups were 1 (95% CI -3 to 5) and -10 (95% CI -15 to -4), respectively in favor of theophylline. Three patients receiving theophylline and 2 receiving placebo had clinically meaningful improvements on the UPSIT (difference 5%, 95% CI -30% to 40%). There were no adverse events, and serum theophylline levels were undetectable in 10/10 patients. Conclusions: While safe, there were no clinically meaningful differences in olfactory change between the two groups except for olfaction-related quality of life, which was better with theophylline. The imprecise estimates suggest future trials will need substantially larger sample sizes or treatment modifications, such as increasing the theophylline dose, to observe larger treatment effects.

Original languageEnglish
Article number103299
JournalAmerican Journal of Otolaryngology - Head and Neck Medicine and Surgery
Issue number2
StatePublished - Mar 1 2022


  • Anosmia
  • Hyposmia
  • Olfaction
  • Quality of life
  • Smell
  • Theophylline
  • Therapeutics
  • Viral


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