Chronic sinusitis was the most frequently reported disease by Americans in the 1993 National Health Interview Survey and is a major contributor to health care costs and decreased productivity. It has recently become apparent that chronic disease is not associated with infection of the paranasal sinuses but is characterized by an eosinophilic/lymphocytic infiltration of the inflamed sinus mucosa. It is also known that there is a close relationship between allergic rhinitis and sinusitis since many subjects with sinusitis are allergic and many allergic subjects suffer from chronic sinus disease. To investigate a potential mechanism for this relationship, we challenged allergic subjects with allergen intranasally and monitored their cellular response in both the nasal and ipsilateral maxillary sinus cavity using lavage. These experiments have yielded exciting preliminary data showing that the number of eosinophils in maxillary sinus secretions increases significantly hours after nasal challenge with allergen but not after sham challenge. Because the nose and the maxillary sinuses are separate cavities, we hypothesize that allergic inflammation in the nose triggers axonal reflexes that lead to the release of neuropeptides within the ipsilateral maxillary sinus cavity. These neuropeptides act locally and promote mediator release from sinus resident cells that result in eosinophil recruitment into the sinus cavity in the hours after allergen challenge of the nose. We hypothesize that histamine, leukotrienes and interleukin 5 produced into the nose and the maxillary sinus will be important for the generation of the eosinophilic response. We will test this hypothesis by measuring these mediators and neuropeptides in maxillary sinus lavages after nasal challenge with allergen and capsaicin, a substance that triggers an axonal reflex. We will also attempt to block the eosinophilic response by local anesthetics and specific receptor antagonists for leukotrienes and histamine. The effect of ongoing allergic or sinus inflammation on the eosinophilic sinus response will also be studied by comparing the response of allergic subjects in and out of their allergy season and subjects with and without chronic sinusitis. Completing this proposal will not only help elucidate the mechanisms underlying the close association between allergic rhinitis and chronic sinusitis but will also be helpful in furthering our understanding of the pathophysiology of the inflammatory response within the paranasal sinuses. This will hopefully help to improve our therapeutic modalities for this enigmatic illness that affects millions of Americans every year.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Immunological Sciences Study Section (IMS)
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Plaut, Marshall
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University of Chicago
Schools of Medicine
United States
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Baroody, Fuad M; Detineo, Marcella; Naclerio, Robert M (2013) Unilateral nasal allergic reactions increase bilateral sinus eosinophil infiltration. J Appl Physiol (1985) 115:1262-7
Baroody, Fuad M; Mucha, Samantha M; Detineo, Marcy et al. (2008) Nasal challenge with allergen leads to maxillary sinus inflammation. J Allergy Clin Immunol 121:1126-1132.e7
Naclerio, Robert; Blair, Christopher; Yu, Xiaohong et al. (2006) Allergic rhinitis augments the response to a bacterial sinus infection in mice: A review of an animal model. Am J Rhinol 20:524-33
Pinto, Jayant M; Elwany, Samy; Baroody, Fuad M et al. (2006) Effects of saline sprays on symptoms after endoscopic sinus surgery. Am J Rhinol 20:191-6
Pinto, Jayant M; Assanasen, Paraya; Baroody, Fuad M et al. (2005) Alpha-adrenoreceptor blockade with phenoxybenzamine does not affect the ability of the nose to condition air. J Appl Physiol 99:128-33
Pinto, Jayant M; Assanasen, Paraya; Baroody, Fuad M et al. (2004) Treatment of nasal inflammation decreases the ability of subjects with asthma to condition inspired air. Am J Respir Crit Care Med 170:863-9
Moinuddin, Rizwan; deTineo, Marcy; Maleckar, Barbara et al. (2004) Comparison of the combinations of fexofenadine-pseudoephedrine and loratadine-montelukast in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol 92:73-9
Saengpanich, Supinda; deTineo, Marcy; Naclerio, Robert M et al. (2003) Fluticasone nasal spray and the combination of loratadine and montelukast in seasonal allergic rhinitis. Arch Otolaryngol Head Neck Surg 129:557-62
Assanasen, Paraya; Baroody, Fuad M; Haney, Lauran et al. (2003) Elevation of the nasal mucosal surface temperature after warming of the feet occurs via a neural reflex. Acta Otolaryngol 123:627-36
Mucha, Samantha M; Baroody, Fuad M (2003) Relationships between atopy and bacterial infections. Curr Allergy Asthma Rep 3:232-7

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