August 2010

Theophylline in Nasal Mucus and Saliva — Effects of Oral Theophylline Treatment

We have shown that the phosphodiesterase (PDE) inhibitor theophylline given orally restores taste and smell function in patients with taste and smell loss. However, the mechanisms by which these effects occur are still unclear. In order to evaluate these effects we measured levels of theophylline in saliva and in nasal mucus after giving oral theophylline. Results of this study demonstrated, for the first time, that, after oral theophylline treatment, theophylline is present in nasal mucus.

Theophylline has been given orally to patients with asthma for many years. In order to monitor its efficacy and toxicity the drug level has been measured in blood and occasionally in saliva. Levels in saliva have been useful in children since they did not have to undergo taking of their blood.

We have used oral theophylline in patients with taste and smell loss to correct these losses. We have shown that theophylline increases levels of saliva and nasal mucus cAMP and cGMP thereby correcting these losses.

We were interested if oral theophylline appeared in nasal mucus and saliva to account for these changes. The drug could interact directly with both salivary and nasal mucus glands and, acting as a phosphodiesterase (PDE) inhibitor, directly increase cAMP and cGMP secretion from these glands. In this sense oral theophylline, through its effects on salivary and nasal mucus glands, would increase saliva and nasal mucus cAMP and cGMP by coming into direct contact with taste buds and olfactory epithelium.

Results demonstrated that at every dose of theophylline given to these patients, from the lowest (200mg) to the highest level (800mg), theophylline is present in nasal mucus and in saliva. Theophylline levels in nasal mucus are usually higher than in saliva. Levels in nasal mucus vary from 58-97% the level found in blood.

These results demonstrate that oral theophylline appears in nasal mucus and in saliva and thereby directly influence both smell and taste function through its action as a PDE inhibitor.

These studies have been submitted for publication in the Journal of Clinical Pathology.