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Reprinted by permission of Arch Otolaryngol Head Neck Surg. 2012; 138(11):1064-1070.

ORIGINAL ARTICLE

Intranasal Theophylline Treatment of Hyposmia and Hypogeusia A Pilot Study

Robert I. Henkin, MD, PhD; Michael Schultz, RPh; Laura Minnick-Poppe, PharmD

Objective : To determine whether intranasal theophyl- line methylpropyl paraben can correct hyposmia and hy- pogeusia. Design : We performed an open-label pilot study in pa- tients with hyposmia and hypogeusia under the follow- ing 3 conditions: (1) before treatment, (2) after oral the- ophylline anhydrous treatment, and (3) after intranasal theophylline treatment. Under each condition, we per- formed subjective evaluations of taste and smell func- tions, quantitative measurements of taste (gustometry) and smell (olfactometry), and measurements of serum theophylline level and body weight. Patients : Ten patients with hyposmia and hypogeusia clinically related to the effects of viral illness, allergic rhi- nitis, traumatic brain injury, congenital hyposmia, and other chronic disease processes were selected. Interventions : Oral theophylline anhydrous, 200 to 800 mg/d for 2 to 12 months, was administered to each pa- tient. This treatment was discontinued for 3 weeks to 4 Setting : The Taste and Smell Clinic inWashington, DC.

months when intranasal theophylline methylpropyl para- ben, 20 µg/d in each naris, was administered for 4 weeks. Main OutcomeMeasures : At termination of each con- dition, taste and smell function was determined subjec- tively, by means of gustometry and olfactometry, with measurement of serum theophylline levels and body weight. Results : Oral theophylline treatment improved taste and smell acuity in 6 patients after 2 to 12 months of treat- ment. Intranasal theophylline treatment improved taste and smell acuity in 8 patients after 4 weeks, with im- provement greater than after oral administration. No ad- verse effects accompanied intranasal drug use. Bodyweight increased with each treatment but was greater after in- tranasal than after oral administration. Conclusions : Intranasal theophylline treatment is safer and more effective in improving hyposmia and hypo- geusia than oral theophylline anhydrous treatment.

Arch Otolaryngol Head Neck Surg. 2012;138(11):1064-1070

L OSS OF SMELL ( HYPOSMIA ) and taste (hypogeusia) are common symptoms that affect many thousands of pa- tients in the United States, as reported by several investigators. 1-4 Effec- tive treatment for these symptoms has been demonstrated only recently and has not been formally established. Before effective treatment to correct loss of smell and taste can be established, a bio- chemical basis for the cause of these symp- toms is necessary. To accomplish this, we determined that these symptoms are com- monly caused by decreased secretion of several growth factors in the saliva and na- sal mucus. The growth factors act on stem cells in taste buds and olfactory epithelial

cells to generate the elegant repertoire of cellular components in these sensory or- gans. 5-11 Growth factor stimulation of these sensory organs is thought to maintain nor- mal taste and smell function. 5-11 If these growth factors were diminished by any of several diseases and pathological condi- tions, then hyposmia and hypogeusia oc- cur. 5,12,13 These conditions and diseases in- clude trace metal deficiencies 14 ; vitamin deficiencies 15,16 ; liver disease 17 ; diabetes mellitus 18 ; other metabolic, 12,13 otolaryn- gological, 19,20 and neurodegenerative dis- orders, including multiple sclerosis, 21-23 Parkinson disease, 24-28 and Alzheimer dis- ease 29-32 ; and other neurological disor- ders. 33 Effective treatment to increase se- cretion of these growth factors is therefore

Author Affi and Smell C Molecular Sensory Dis DC (Dr Hen Care, Earth (Mr Schultz College of P Missouri (D

Author Affiliations: The Taste and Smell Clinic, Center for Molecular Nutrition and Sensory Disorders, Washington, DC (Dr Henkin); Foundation Care, Earth City, Missouri (Mr Schultz); and St Louis College of Pharmacy, St Louis, Missouri (Dr Minnick-Poppe).

ARCH OTOLARYNGOL HEAD NECK SURG/VOL 138 (NO. 11), NOV 2012 WWW.ARCHOTO.COM

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