In vivo determination of mouse olfactory mucus cation concentrations in normal and inflammatory states.
OBJECTIVE
Olfaction is impaired in chronic rhinosinusitis (CRS). The study has two aims: (1) to determine whether changes in cation concentration occur in the olfactory mucus of mice with CRS, which may affect chemo-electrical transduction, (2) and to examine whether these alterations are physiologically significant in humans.


METHODS
Animal study in mice and translational study in humans.


METHODS
Inflammation was induced by sensitization and chronic exposure of 16 C57BL/6 mice to Aspergillus fumigatus. The control group included 16 untreated mice. Ion-selective microelectrodes were used to measure free cation concentrations in the olfactory mucus of 8 mice from each treatment group, while the remaining mice were sacrificed for histology. To validate the findings in the animal model, olfactory threshold was measured in 11 healthy human participants using Sniffin' Sticks before and after nasal irrigation with solutions that were composed of either of the cation concentrations.


RESULTS
In 8 mice, olfactory mucus of chronically inflamed mice had lower [Na(+)] (84.8±4.45 mM versus 93.73±3.06 mM, p = 0.02), and higher [K(+)] (7.2±0.65 mM versus 5.7±0.20 mM, p = 0.04) than controls. No difference existed in [Ca(2+)] (0.50±0.12 mM versus 0.54±0.06 mM, p = 0.39). In humans, rinsing with solutions replicating ion concentrations of the mouse mucosa with chronic inflammation caused a significant elevation in the median olfactory threshold (9.0 to 4.8, p = 0.003) but not with the control solution (8.3 to 7.8, p = 0.75).


CONCLUSIONS
Chronic inflammation elevates potassium and lowers sodium ion concentration in mice olfactory mucus. Nasal irrigation with a corresponding solution induced olfactory threshold shift in humans.
Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Senthil
S
Selvaraj
Kevin
K
Liu
Alan M
AM
Robinson
Victoria A
VA
Epstein
David B
DB
Conley
Robert C
RC
Kern
Claus-Peter
CP
Richter
D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D002412:Cations / Q000737:chemistry*; D004195:Disease Models, Animal; D047093:Eosinophil Major Basic Protein / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007477:Ions / Q000737:chemistry; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D009093:Mucus / Q000737:chemistry*; D055556:Nasal Lavage; D009831:Olfactory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012220:Rhinitis / Q000378:metabolism; D012852:Sinusitis / Q000378:metabolism; D055815:Young Adult
D000485:Allergens; D002412:Cations; D007477:Ions; D047093:Eosinophil Major Basic Protein