Around 40% of the world's population is now impacted by allergic disease and this figure continues to rise. It is now understood that allergic disease arises from complex interactions between genetic and environmental factors. Exposure to allergens such as dust mites and pollen, as well as air pollutants such as diesel exhaust particulates, can alter the ability of critical genes to be expressed appropriately, a process known as epigenetic modification. The epigenetic modifications induced by allergens and pollutants appears to be reversible, thus providing a mechanism by which allergic disease can be treated. Budesonide (Rhinocort®) is a corticosteroid nasal spray commonly used to treat allergy symptoms. While the anti- inflammatory and other pharmacological aspects of budesonide are well understood, recent studies have suggested that budesonide may also work by reversing the epigenetic modifications caused by allergen exposure, although this has not been examined in the context of real-world exposures in humans.

This study aims to harness the power of epigenetic analysis to determine whether the epigenetic landscape in patients suffering from allergic disease can be modified by the administration of budesonide. It will fill critical gaps in understanding of epigenetic effects and provide information to examine the connection between environmental impacts and treatment effects. The research will expand the mechanistic understanding of the therapeutic effects of budesonide for relief of nasal rhinitis symptoms and may reveal new mechanisms that could improve treatment of allergies or pollution exposure, or serve as a tool for evaluating future therapies. If this venture is successful, it will serve as a model for studying and optimizing the epigenetic effects of other treatments and other diseases.

To test this, the investigators have planned for two treatment trials where participants will act as both the control and tester (crossover design method). Participants will be provided a randomized treatment order of either 1) Budesonide (Rhinocort) or 2) placebo (no medication) nasal spray for the treatment trial. Participants will go through a series of nasal sampling, symptoms questionnaires, nasal inhalation flow readings during the in-person visits at the hospital. Investigators will also attempt to mimic allergen and pollution exposures, and track how the treatment affects one's nasal responses during visits. On days where participants do not have in-person visits, participants will continue using the treatment product on a daily basis. After one cycle of treatment, participants will go through a wash-out period before starting the second cycle with the opposite treatment (Budesonide (Rhinocort)/placebo).

Investigators are not expecting that participants' responses to the treatments or exposures will be noticeable to the participants. Any responses that may occur will probably only be detectable through careful examination of the collected nasal samples on a genetic basis. However, being able to understand the subtle changes will help investigators optimize and better understand the use of these treatments in the future.

Inclusion Criteria:

• Healthy men and women aged 18 - 65 years. (Female subjects must be postmenopausal, surgically sterile or using medically accepted contraceptive means, as judged by the investigator).
• Asymptomatic subjects (not experiencing rhinitis symptoms at the time of screening).
• A clinical diagnosis of allergic rhinitis (dust mite, grass mix or tree mix) for at least the previous two years.
• Subjects with a need of treatment for their nasal symptoms during the pollen season of such severity that it required pharmacological therapy each year for the last two consecutive years.
• Willingness to participate as indicated by a signed informed consent. Signed consent must be obtained from the subject prior to start of any study-related procedures.
• Availability and ability for all planned site visits
• A nasal allergen challenge resulting in at least five sneezes and/or a recorded score of >2 in either nasal obstruction or runny nose

Exclusion Criteria:

• Subjects with confirmed hypersensitivity to budesonide.
• Subjects with previous or current respiratory- cardiovascular-, renal-, liver-, endocrinological or other diseases or conditions which may influence the subject's participation in the study or the result hereof, as judged by the investigator.
• Subjects with a planned hospitalization or planned blood-donation during the study.
• Women who are pregnant or nursing.
• Diseases or conditions which might interfere with the evaluation of efficacy and safety:
• Subjects with structural abnormalities of the nose (e.g. septal deviation, nasal polyps) or other diseases (infectious rhinitis, sinusitis, rhinitis medicamentosa and atrophic or non- allergic rhinitis) which could cause significant nasal obstruction or other symptoms which could have any significant influence on the investigated disease as judged by the investigator.
• History of asthma.
• PAR (with an exception, see inclusion criterion 3).
• Subjects allergic to other allergens occurring during the study period.
• Systemic corticosteroid use within 2 months, topical corticosteroid use within 2 weeks, antihistamine use within 1 week, leukotriene antagonist use within one week or immunotherapy within 2 years of baseline visit (or stop at screening)
• Upper respiratory infection within 2 weeks of baseline visit
• Use of tobacco within 1 year of baseline
• Chronic medical condition that could interfere with evaluation of rhinitis endpoints (e.g. allergic skin conditions, active infections, asthma, etc.)

Visually indistinguishable placebo and budesonide nasal sprays will be coded by research staff not connected to the study and pre-packaged for participants. All assays will be performed by personnel who do not know the exposure conditions of individual samples.