Relative Resistance to Oral Theophylline Treatment in Patients With Hyposmia Manifested by Decreased Secretion of Nasal Mucus Cyclic Nucleotides

Henkin, Robert I.; Velicu, Irina; Schmidt, Loren

doi:10.1097/maj.0b013e3181f1fdc8

Cited by 19 publications

(15 citation statements)

References 47 publications

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“…40,42 The earliest this improvement was measured was after 2 months of treatment, but maximal improvement varied from 4 to 12 months. These results also demonstrate that oral theophylline was effective in improving hypogeusia in the same time frame as improvement in smell acuity.…”

Section: Commentmentioning

confidence: 99%

“…52 This delivery mechanism may also avoid development of drug resistance that has occurred with oral theophylline. 42 In addition, because more drug presumably contacts the olfactory epithelium with intranasal than with oral theophylline, direct nasal instillation may activate more olfactory receptors than does oral administration.…”

Section: Commentmentioning

confidence: 99%

“…40 Subsequent investigators have used other oral phosphodiesterase inhibitors to correct hyposmia. 41 An open-label study also demonstrated that, as nasal mucus cAMP and cGMP levels increased, hyposmia was corrected, 42 whereas in patients in whom these moieties did not increase, hyposmia was not corrected. These results suggested that some patients may be resistant to treatment with oral theophylline.…”

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confidence: 99%

“…These results suggested that some patients may be resistant to treatment with oral theophylline. 42 However, successful treatment with oral theophylline that increased nasal mucus levels of cAMP and cGMP required increased theophylline doses, 40 sometimes prolonged treatment duration, 40 and endurance of adverse effects, including restlessness, gastrointestinal tract discomfort, sleep difficulties, tachycardia, and other unwanted symptoms. 40,43,44 Theophylline treatment also required regular determinations of blood theophylline levels to ensure adequate drug absorption and lack of toxic effects.…”

mentioning

confidence: 99%

“…45 These results were consistent with improvement in smell function as demonstrated in patients with hyposmia in the prior clinical trial. 40 Results of these studies 40,42 and efforts to improve therapeutic efficacy and reduce adverse effects of oral theophylline administration made it logical to administer the drug intranasally. In this manner, the drug could affect olfactory receptors more directly without causing the systemic adverse effects associated with oral therapy.…”

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confidence: 99%

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Intranasal Theophylline Treatment of Hyposmia and Hypogeusia

Henkin¹,

Schultz²,

Minnick-Poppe³

2012

Arch Otolaryngol Head Neck Surg

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To determine whether intranasal theophylline methylpropyl paraben can correct hyposmia and hypogeusia. Design:We performed an open-label pilot study in patients with hyposmia and hypogeusia under the following 3 conditions: (1) before treatment, (2) after oral theophylline anhydrous treatment, and (3) after intranasal theophylline treatment. Under each condition, we performed subjective evaluations of taste and smell functions, quantitative measurements of taste (gustometry) and smell (olfactometry), and measurements of serum theophylline level and body weight.Setting: The Taste and Smell Clinic in Washington, DC.Patients: Ten patients with hyposmia and hypogeusia clinically related to the effects of viral illness, allergic rhinitis, 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 patient. This treatment was discontinued for 3 weeks to 4 months when intranasal theophylline methylpropyl paraben, 20 µg/d in each naris, was administered for 4 weeks.Main Outcome Measures: At termination of each condition, taste and smell function was determined subjectively, 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 treatment. Intranasal theophylline treatment improved taste and smell acuity in 8 patients after 4 weeks, with improvement greater than after oral administration. No adverse effects accompanied intranasal drug use. Body weight increased with each treatment but was greater after intranasal than after oral administration.Conclusions: Intranasal theophylline treatment is safer and more effective in improving hyposmia and hypogeusia than oral theophylline anhydrous treatment.

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Section: Commentmentioning

confidence: 99%

Section: Commentmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Intranasal Theophylline Treatment of Hyposmia and Hypogeusia

Henkin¹,

Schultz²,

Minnick-Poppe³

2012

Arch Otolaryngol Head Neck Surg

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International consensus statement on allergy and rhinology: Olfaction

Patel

Holbrook

Turner

et al. 2022

Int Forum Allergy Rhinol

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Background:The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). Methods: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. Results:The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. Conclusion:This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.

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