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

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Abstract

Background

To test the hypothesis that theophylline is effective in correcting smell loss in patients with hyposmia.

Methods

Three hundred twelve patients with smell loss (hyposmia) were evaluated to determine characteristics of their loss by psychophysical measurements of detection and recognition thresholds, magnitude estimation and hedonic values for 4 odors (pyridine, nitrobenzene, thiophene, and amyl acetate) by use of a forced-choice 3-stimuli staircase design previously documented in a double-blind study. Patients were then treated in a fixed design open-label clinical trial with oral theophylline. Drug was given in equal divided doses from 200 to 800 mg daily for 2-to 8-month periods and subjective and psychophysical measurements of smell function and blood theophylline levels were measured; results were compared with those obtained before treatment.

Results

Subjective smell loss improved in 157 (50.3%) patients; smell function was considered normal by 34 (21.7%). Overall, 10.9% of patients in the study considered smell function returned to normal. However, measurements of mean detection and recognition thresholds improved significantly at each drug level; measurements of mean magnitude estimation and hedonic also improved. Improvement was greater at drug doses of 600 and 800 mg than at 200 or 400 mg. Once improvement occurred, as long as treatment was maintained, it persisted for as long as follow-up was measured.

Conclusion

Theophylline was effective in improving smell function in patients with smell loss. Improvement persisted as long as treatment was continued, which extended from 6 to 72 months.

Section snippets

METHODS

All studies were performed at The Taste and Smell Clinic, Washington, DC between June 2000 and February 2007 and constitute studies on consecutive patients who presented to the clinic because of loss of smell function and who exhibited salivary32 and nasal mucus33 levels of cAMP and cGMP below the normal mean. Studies were approved by the institutional review board of the Georgetown University Medical Center; all patients gave informed consent to participate in this study.

There were 312

Comparison of Smell Function in Normal Subjects and in Untreated Patients With Hyposmia

Results of measurements for DT, RT, ME, and H in untreated patients indicated significant impairment of smell function compared with normal subjects (Table 2). For DT and RT in untreated patients responses were significantly higher (less sensitive) than in normals (Table 2); ME responses were significantly lower (less sensitive) than in normals. H responses were significantly lower (less pleasant) for amyl acetate and nitrobenzene (odors usually considered pleasant) and significantly lower for

DISCUSSION

These results indicate that 157 of the 312 patients in the study (50.3%) were responsive to treatment with theophylline. Of these, 34 (21.7%) considered their smell function returned to normal levels. Overall 10.9% of all patients in the study considered their smell function had returned to normal. Improvement in smell function, once occurred, persisted as long as treatment was measured.

Initial studies were made at 2-to 6-month intervals after drug initiation. Subjective responses indicated

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    Presented, in part, at Experimental Biology, San Diego, CA, April, 2008.

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