An Open-Label Controlled Trial of Theophylline for Treatment of Patients With Hyposmia

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

doi:10.1097/maj.0b013e3181914a97

Cited by 92 publications

(104 citation statements)

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“…To test this hypothesis, a previous study from our institution administered oral theophylline anhydrous to 312 patients with hyposmia and hypogeusia in an open-label controlled clinical trial. 40 Results of this study demonstrated that oral theophylline treatment successfully corrected hyposmia in more than 50% of these patients. 40 Subsequent investigators have used other oral phosphodiesterase inhibitors to correct hyposmia.…”

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confidence: 74%

“…40 Results of this study demonstrated that oral theophylline treatment successfully corrected hyposmia in more than 50% of these patients. 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.…”

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confidence: 74%

“…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. 40 These efforts limited use of this orally administered drug.…”

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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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Intranasal Theophylline Treatment of Hyposmia and Hypogeusia

Henkin¹,

Schultz²,

Minnick-Poppe³

2012

Arch Otolaryngol Head Neck Surg

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“…3 And recently, intranasal theophylline has been even more efficient in helping these patients restore their smell function.…”

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“…3 And recently, intranasal theophylline has been even more efficient in helping these patients restore their smell function. 4 It is up to otolaryngologists to understand the extent of this epidemic and to respond to it with the same energy and enthusiasm that they extend to their surgical practice for which they were well trained.…”

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The Hidden Epidemic of Smell Loss (Hyposmia) in the United States

Henkin¹

2015

Otolaryngol Open J

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EditorialThere is a hidden epidemic of hyposmia in the United States. While most otolaryngologists may see one or two patients with hyposmia yearly there are as many as 21 million people in the United States with hyposmia.1 Most of these patients experienced hyposmia following an influenza-like infection.2 Data suggest that there are 30 million patients who experience a flu-like illness yearly; our data suggest that about 1% of these patients develop permanent hyposmia or about three million people develop and suffer with this symptom on a yearly basis. As many as two million patients who have what can be termed allergic rhinitis suffer with hyposmia on a chronic basis.2 Otolaryngologists do see these patients but if they do not exhibit rhinitis, sinusitis or nasal polyps the patient's hyposmia may not be paramount in their evaluation or treatment. Patients with hyposmia after a traumatic brain injury represent a third major etiology of hyposmia with as many as 500,000 patients exhibiting a persistent hyposmia after their head injury.2 Hyposmia associated with aging, head and neck radiation or chemotherapy, Parkinson's disease or other metabolic or neurological issues constitute a part of this epidemic which is not recognized by otolaryngologists as a major medical problem.While hyposmia may not be life threatening for most of these patients their lives are inhibited by their inability to obtain flavor from food, enjoy social events around meals or to smell both pleasant and unpleasant or dangerous odors. Most patients are deeply disturbed and can become depressed by this loss and search unsuccessfully for methods to restore their smell function.The major problems related to this epidemic are lack of understanding of the mechanisms responsible for it, how to evaluate it or how to treat it.Most patients with hyposmia do not have an anatomical or neurological etiology as the cause of their loss. Most patients exhibit hyposmia related to abnormalities of their olfactory receptors which are damaged by the viral RNA associated with their influenza or by an underlying immunological pathology associated with their rhinitis. 2Most otolaryngologists do not have the equipment to evaluate quantitatively the sensory changes about which the patients complain. We have established specific testing techniques to help to evaluate these patients.2 Results of these tests define the roles of the receptors, the brain and the interaction between the receptors and brain play in hyposmia.Most otolaryngologists are unaware that drugs are available to treat these patients. 2Many studies have demonstrated that treatment with oral theophylline has been successful in restoring smell function in many of these patients. 3 And recently, intranasal theophylline has been even more efficient in helping these patients restore their smell function. 4It is up to otolaryngologists to understand the extent of this epidemic and to respond to it with the same energy and enthusiasm that they extend to their surgical practice for which they were well trai...

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Interleukin 6 in Hyposmia

Henkin

Schmidt

Velicu

2013

JAMA Otolaryngol Head Neck Surg

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Compared with controls, IL-6 in patients was significantly elevated in plasma, saliva, and nasal mucus. Because IL-6 is a proinflammatory cytokine, these changes can relate to local or systemic inflammatory processes, which can be a cause or a result of pathological processes associated with hyposmia. These results support the concept that hyposmia has a biochemical basis and IL-6 may play a role in biochemical pathological processes underlying hyposmia and its treatment.

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An Open-Label Controlled Trial of Theophylline for Treatment of Patients With Hyposmia

Cited by 92 publications

References 33 publications

Intranasal Theophylline Treatment of Hyposmia and Hypogeusia

Intranasal Theophylline Treatment of Hyposmia and Hypogeusia

The Hidden Epidemic of Smell Loss (Hyposmia) in the United States

Interleukin 6 in Hyposmia

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