Investigation of the Impact of Smoking Status on Allergen-induced Nasal Airway Inflammation Using a Cat Hair (Felis Domesticus) Extract Nasal Allergen Challenge Model

The recent increase in popularity of e-cigarettes for smoking cessation or in combination
with conventional cigarettes has let to safety concerns regarding their potential role in
respiratory disease. These tobacco alternatives devices were initially perceived as a "safer"
alternative to cigarettes and were marketed without much known about their health effects.
Increasing evidence that while they contain fewer toxins and carcinogens than conventional
cigarettes, they do involve delivery of ultrafine particles to the lower airways and can
contain heavy metals and other chemicals. Tobacco Smoke may augment allergic inflammation
resulting from allergic rhinitis and/or asthma. Animal models of allergic asthma demonstrate
aggravation of allergen -induced airway inflammation following inhalation of e-cig cartridge
solution, with increased airway eosinophil infiltration, production of Th2 cytokines, and
airway hyperresponsivness. In vitro studies in human tissues have demonstrated
pro-inflammatory responses in a similar way as tobacco smoke, yet a head-to-head comparison
of the effects of these two exposures has not been performed in humans.

Use of tobacco products remains a pervasive problem in our society and around the world, with
significant impact on respiratory health and quality of life. With the emergence of new
non-tobacco based nicotine products like e-cigarettes, it is important to understand the
impact these substances have on respiratory health and disease. The aim o f this study is to
study the impact of these products on allergic inflammation in cat allergic subjects who
already routinely use e-cigarettes and to compare their response to those of cigarette
smokers and non-smokers. A thorough understanding of the potential health impacts of tobacco
alternative substances in seeded, especially given the rising popularity of such products
with adolescents and young adults to whom these substances have particular appeals given the
purported safety: and variety of flavors to chose from.

Inclusion Criteria:

1. Males and females age 18-50 years

2. Specific allergy to cat hair Felis domesticus confirmed by positive immediate skin
test response

3. Subjects may be enrolled with mild asthma if a Forced Expiratory Volume in 1 second
(FEV1) of at least 80% of predicted and a Forced Expiratory Volume in 1 second to
Forced Vital Capacity (FVC) ratio (FEV1/FVC ratio) of at least .75 (without use of
bronchodilator medications for 12 hours), consistent with lung function of persons
with mild episodic or mild persistent asthma is demonstrated. For the purpose of this
protocol, an asthmatic individual will be defined as having a) positive methacholine
challenge with a provocative concentration of methacholine producing a 20% fall in
FEV1 (PC20 methacholine) with less than or equal to 10 mg/ml; OR b) physician
diagnosed asthma with symptoms and chronic daily therapy consistent with the mild
asthma

4. Ability to withhold antihistamine medications for one week prior to baseline and
allergen challenge visits.

5. Subjects must be able and willing to give informed consent.

6. Subjects will be classified as tobacco smokers, e-cigarette users, or non-smokers

Exclusion Criteria:

1. Any chronic medical condition considered by the PI as a contraindication to the
allergen challenge study including significant cardiovascular disease, diabetes
requiring medication, chronic renal disease, bleeding disorder, or chronic thyroid
disease.

2. Physician directed emergency treatment for an asthma exacerbation within the preceding
12 months.

3. Use of systemic steroid therapy within the preceding 12 months for treatment of an
asthma exacerbation.

4. Use of inhaled or nasal steroids, cromolyn or leukotriene receptor antagonists
(Montelukast or Zafirkulast) within the past month (except for use of cromolyn
exclusively prior to exercise).

5. Use of allergen immunotherapy.

6. Use of daily theophylline within the past month.

7. Use of nasal medications that might alter the response to nasal allergen challenge
including anti-inflammatory and anti-histamine agents within one week of challenge.

8. Inability to withhold inhaled or oral bronchodilator medications for 12 hours prior to
allergen challenge.

9. Pregnancy or nursing a baby.

10. Women of child-bearing age who are not using dependable contraception (such as birth
control pills, IUD, estrogen patches) or who are not completely abstinent.

11. Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a
clearly recognized viral induced asthma exacerbation) which would be characteristic of
a person of moderate or severe persistent asthma as outlined in the current NHLBI
guidelines for diagnosis and management of asthma.

12. Exacerbation of asthma more than 2x/week which would be characteristic of a person
with moderate or severe persistent asthma as outlined in the current NHLBI guidelines
for diagnosis and management of asthma.

13. Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest
tightness) which would be characteristic of a person of moderate or severe persistent
asthma as outlined in the current NHLBI guidelines for diagnosis and management of
asthma. (Not to include prophylactic use of albuterol prior to exercise).

14. Viral upper respiratory tract infection within 4 weeks of challenge.

15. Any acute infection requiring antibiotics within 4 weeks of challenge.

16. Participating in an allergen inhalation study within 2 weeks of this challenge or use
of any investigational agent within the last 30 days.

17. Use of tricyclic antidepressants or beta-blockers.

18. Use of MAO inhibitors or any medications known to interfere with the treatment of
anaphylaxis.

19. Subjects with a history of immunologic disease or undergoing immune suppression for
cancer or other diseases.

20. Subjects with acute inflammatory conditions in the nose or paranasal sinuses, such as
sinusitis.