cAMP and cGMP in nasal mucus related to severity of smell loss in patients with smell dysfunction

Abstract

Clin Invest Med 2008; 31 (2): E78-E84. AbstractPurpose: To evaluate nasal mucus levels of cAMP and cGMP in patients with taste and smell dysfunction with respect to severity of their smell loss. Methods: cAMP and cGMP were measured in nasal mucus using a sensitive spectrophotometric 96 plate ELISA technique. Smell loss was measured in patients with taste and smell dysfunction by standardized psychophysical measurements of olfactory function and classified by severity of loss into four types from most severe to least severe such that anosmia > Type I hyposmia > Type II hyposmia > Type III hyposmia. Measurements of nasal mucus cyclic nucleotides and smell loss were made independently. Results: As smell loss severity increased stepwise cAMP and cGMP levels decreased stepwise [cAMP, cGMP (in pmol/ml); anosmia -0.004, 0.008: Type I hyposmia -0.12±0.03, 0.10±0.03: Type II hyposmia -0.15±0.02, 0.16±0.01: Type III hyposmia -0.23±0.05, 0.20±0.15]. Conclusions: These results confirm the association of biochemical changes in cyclic nucleotides with systematic losses of smell acuity. These results confirm the usefulness of the psychophysical methods we defined to determine the systematic classification of smell loss severity. These changes can form the basis for the biochemical definition of smell loss among some patients with smell loss as well as for their therapy.

Sonic Hedgehog in Nasal Mucus is a Biomarker for Smell Loss in Patients with Hyposmia

“…However, there are many moieties in nasal mucus in humans not identified through these and other analyses [13]. Chief among these are adenylyl cyclases [14,15] and their downstream metabolites cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) [16,17]. These latter moieties were found decreased in hyposmic patients compared to normal subjects [16,17].…”

“…Chief among these are adenylyl cyclases [14,15] and their downstream metabolites cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) [16,17]. These latter moieties were found decreased in hyposmic patients compared to normal subjects [16,17]. Sonic hedgehog (Shh) has been characterized as a critical factor in cellular growth and development of taste receptors [18,19] with its absence associated with inhibition of growth and development of receptors of these sensory organs [20]; however, it has not been identified to play a role in olfaction per se.…”

Intranasal Theophylline Treatment of Hyposmia and Hypogeusia

“…Each patient had undergone previous evaluation before any drug treatment, 12,13 followed by treatment with oral theophylline. These patients had hyposmia and hypogeusia and exhibited levels of cAMP and cGMP lower than their respective reference ranges in the saliva 35,36 and nasal mucus 37,38 before theophylline treatment. These 10 patients were selected from the group undergoing previous evaluation and treatment for the intranasal trial because (1) their response to oral theophylline was subjectively submaximal; (2) they developed adverse effects after attempts to increase the drug dose to obtain a more maximal clinical response, thus limiting the administered drug dose; and (3) they resided in an area in close proximity to The Clinic, which made their frequent return visits to The Clinic more practical for any additional clinical trial.…”

“…33 Effective treatment to increase secretion of these growth factors is therefore necessary to improve hypogeusia and hyposmia 5,12,13 and return taste and smell function to normal as demonstrated by several previous studies. 5,12,13 To understand more about these processes, a comprehensive study of many patients with loss of smell and taste determined that levels of the salivary 34,35 and nasal mucus 36,37 growth factors cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were lower than in healthy subjects and were responsible for the onset of hyposmia and hypogeusia in many of these patients. 38,39 Indeed, as hyposmia increased in severity, levels of these salivary 35 and nasal mucus 37 growth factors decreased in a consistent manner.…”

“…With assistance of an established pharmaceutical company, the drug was packaged for sterile, intranasal delivery. Using this device, an open-label, singlesource, controlled pilot study in 10 patients with hyposmia and hypogeusia and with levels of parotid saliva 35,36 and nasal mucus 37,38 cAMP and cGMP below the reference range was performed to determine safety and to compare smell and taste responses after intranasal theophylline treatment, with patient responses before any treatment and after oral theophylline treatment.…”