A variety of symptoms linked to indoor air pollution, including eye, nose, and throat irritation (as well as reflex nasal congestion, rhinorrhea, and sinus headache) are either mediated (or triggered) by trigeminal chemoreception. The premise that humans exhibit significant inter-individual variation in nasal trigeminal irritant sensitivity is one that has been suggested on both clinical and epidemiologic grounds, but experimentally has been incompletely investigated. The purpose of this series of experiments is to systematically explore the influence of personal factors -including age, gender, and allergic rhinitis status- on nasal irritant sensitivity, using stratified samples of non-asthmatic subjects aged 18-69 years. Operationally, """"""""nasal irritant sensitivity"""""""" will include both perceptual acuity (the ability of an individual to detect an irritant gas or vapor) and physiologic reactivity (the tendency of individuals to experience reflex-mediated physiologic changes when exposed to irritants). For perceptual acuity, two distinct experimental systems will be employed: detection thresholds using odorless irritant (CO2), and localization thresholds for an odorous volatile organic compound (VOC). Nasal physiologic reactivity will be studies by examining changes in nasal airway resistance (NAR) after both chemical irritant (low-level chlorine) and pharmacologic (aerosolized histamine) provocation. Finally, biochemical markers of mast cell degranulation (tryphase) and neuro-immune modulation (nerve growth factor) will be assayed in nasal lavage fluid pre- and post chemical provocation in a subset of subjects. Issues of test-retest stability and cross agent generalizability of sensory tests will be examined, as will the degree of correlation between individual perceptual acuity and physiologic reactivity. The overall goals include: 1) to better understand heterogeneity of upper airway symptom reporting in polluted environments; 2) to evaluate the relationship between functional subcomponents of """"""""nasal irritant sensitivity""""""""; 3) to further standardize psychophysical and provocation testing protocols for possible use in clinical and/or epidemiologic settings; and 4) to explore the pathophysiology of the nasal response to irritants, including selected interactions between the sensory and immune systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES010424-02
Application #
6382359
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Mastin, Patrick
Project Start
2000-09-01
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
2
Fiscal Year
2001
Total Cost
$189,000
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Shusterman, D (2007) Trigeminally-mediated health effects of air pollutants: sources of inter-individual variability. Hum Exp Toxicol 26:149-57
Shusterman, Dennis; Matovinovic, Elizabeth; Salmon, Andrew (2006) Does Haber's law apply to human sensory irritation? Inhal Toxicol 18:457-71
Shusterman, Dennis; Tarun, Alice; Murphy, Mary Alice et al. (2005) Seasonal allergic rhinitic and normal subjects respond differentially to nasal provocation with acetic acid vapor. Inhal Toxicol 17:147-52
Rigau, Jordi; Farre, Ramon; Trepat, Xavier et al. (2004) Oscillometric assessment of airway obstruction in a mechanical model of vocal cord dysfunction. J Biomech 37:37-43
Matovinovic, E; Solberg, O; Shusterman, D (2003) Epidermal growth factor receptor - but not histamine receptor - is upregulated in seasonal allergic rhinitis. Allergy 58:472-5
Shusterman, D; Avila, P C (2003) Real-time monitoring of nasal mucosal pH during carbon dioxide stimulation: implications for stimulus dynamics. Chem Senses 28:595-601
Shusterman, Dennis; Murphy, Mary Alice; Balmes, John (2003) Influence of age, gender, and allergy status on nasal reactivity to inhaled chlorine. Inhal Toxicol 15:1179-89
Tarun, Alice S; Bryant, Bruce; Zhai, Wenwu et al. (2003) Gene expression for carbonic anhydrase isoenzymes in human nasal mucosa. Chem Senses 28:621-9
Shusterman, Dennis (2003) Toxicology of nasal irritants. Curr Allergy Asthma Rep 3:258-65
Shusterman, D; Balmes, J; Avila, P C et al. (2003) Chlorine inhalation produces nasal congestion in allergic rhinitics without mast cell degranulation. Eur Respir J 21:652-7

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