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. (Mitey Nose)

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.

Study Overview

• Status: Terminated
• Conditions: Healthy Participants; Tobacco Smokers
• Intervention / Treatment: Biological: Der f

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7310
      • UNC Center for Environmental Medicine, Asthma and Lung Biology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Der f treated Non-smoker	Biological: Der f; Nasal administration of Dermatophagoides farinae with 100 allergen units (AU), 500 AU, and finally 1000 AU; Other Names: (Der f)
OTHER: Der f treated Cigarette smoker	Biological: Der f; Nasal administration of Dermatophagoides farinae with 100 allergen units (AU), 500 AU, and finally 1000 AU; Other Names: (Der f)
OTHER: Der f treated E-cig user	Biological: Der f; Nasal administration of Dermatophagoides farinae with 100 allergen units (AU), 500 AU, and finally 1000 AU; Other Names: (Der f)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Eosinophils Per mL in Nasal Lavage Fluid (NLF)	NLF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge. The protocol was amended to replace this outcome using Eosinophilic Cationic Protein (ECP) in Nasal Epithelial Lining Fluid (NELF).	Baseline, 4 hours post-allergen challenge
Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF)	NELF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge.	baseline, 4 hours post-allergen challenge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Interleukin-31 (IL-31) Concentrations in NELF	NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.	Pre- and 4 hours-post nasal allergen challenge
Mean Change in Interleukin-5 (IL-5) Concentrations in NELF	NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.	baseline, 4 hours post-allergen challenge
Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF	NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.	baseline, 4 hours post-allergen challenge
Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF	NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.	baseline, 4 hours post-allergen challenge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal Epithelial Cell Messenger Ribonucleic Acid (mRNA) Expression	Nasal epithelial cell biopsies will be collected at baseline and 4 hours post- nasal allergen challenge. Gene expression changes will be quantified using quantitative real-time polymerase chain reaction (qRT-PCR).	Baseline, 4 hours post- nasal allergen challenge

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 27, 2017
• Primary Completion (ACTUAL): April 16, 2018
• Study Completion (ACTUAL): April 23, 2018

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: January 13, 2017
• First Posted (ESTIMATE): January 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 4, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: E-cig smokers
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 16-1622; P50HL120100-05 (NIH)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No