Clinical trial NCT03023397: Evaluation of the Effect of a Nasal Allergen Challenge With Dermatophagoides Farinae Extract on Nasal Airway Inflammation in Allergic Individuals, Comparing E-cigarette Users to Cigarette Smokers and Non-smokers.
Official title: Evaluation of the Effect of a Nasal Allergen Challenge With Dermatophagoides Farinae Extract on Nasal Airway Inflammation in Allergic Individuals, Comparing E-cigarette Users to Cigarette Smokers and Non-smokers.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Participants
Tobacco Smokers
Keywords: E-cig smokers
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-01-18
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this pilot study is to evaluate allergen-induced nasal airway inflammation following nasal application of Dermatophagoides farinae (Der f), or house dust mite, extract in e-cigarette users, cigarette smokers, and non-smokers.

Detailed description: The recent increase in popularity of e-cigarettes for smoking cessation or in combination with conventional cigarettes has led to safety concerns regarding their potential role in respiratory disease. These tobacco alternative devices were initially perceived as a "safer" alternative to cigarettes and were marketed without much known about their health effects. Increasing evidence demonstrates 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 to e-cig vapour extract yet have not evaluated the effects of e-cig usage on allergic inflammation in human airways. Current evidence suggests that e-cigarette use augments allergic 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 of this study is to study the impact of these products on allergic inflammation in house dust mite-allergic subjects who already routinely use e-cigarettes and to compare their responses to those of cigarette smokers and non-smokers. A thorough understanding of the potential health impacts of tobacco alternative substances is needed, especially given the rising popularity of such products with adolescents and young adults to whom these substances have particular appeal given their purported "safety" and variety of flavors to choose from.

Eligibility criteria: Inclusion Criteria:

1. Specific allergy to house dust mite D. farinae confirmed by positive immediate skin test response
2. Subjects will either be non-asthmatic or have mild asthma characterized by an Forced expiratory volume in one second (FEV1) of at least 80% of predicted to Forced vital capacity (FVC) ratio of at least .75
3. Subjects will be classified as tobacco smokers, e-cigarette users, or non-smokers according to the following guidelines.
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.

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 zafirlukast ) within the past month (except for use of cromolyn exclusively prior to exercise).
5. Subjects who smoke marijuana or use illicit drugs will be excluded.
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, intrauterine device (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 or other acute inflammatory conditions of the nose or paranasal sinuses, such as sinusitis, 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 other investigational agent within the last 30 days.
17. Use of tricyclic antidepressants or beta-blockers.

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Primary outcomes:
measure: Mean Change in Eosinophils Per mL in Nasal Lavage Fluid (NLF)
timeFrame: Baseline, 4 hours post-allergen challenge
measure: Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF)
timeFrame: baseline, 4 hours post-allergen challenge
Secondary outcomes:
measure: Mean Change in Interleukin-31 (IL-31) Concentrations in NELF
timeFrame: Pre- and 4 hours-post nasal allergen challenge
measure: Mean Change in Interleukin-5 (IL-5) Concentrations in NELF
timeFrame: baseline, 4 hours post-allergen challenge
measure: Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF
timeFrame: baseline, 4 hours post-allergen challenge
measure: Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF
timeFrame: baseline, 4 hours post-allergen challenge
Other outcomes:
measure: Nasal Epithelial Cell Messenger Ribonucleic Acid (mRNA) Expression
timeFrame: Baseline, 4 hours post- nasal allergen challenge
Locations:
city: Chapel Hill
country: United States
facility: UNC Center for Environmental Medicine, Asthma and Lung Biology
state: North Carolina
Study officials:
affiliation: University of North Carolina
name: Michelle Hernandez, MD
role: PRINCIPAL_INVESTIGATOR
References: