Healthy Participants, Tobacco Smokers
Conditions
Keywords
E-cig smokers
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.
Interventions
BIOLOGICALDer f
Nasal administration of Dermatophagoides farinae with 100 allergen units (AU), 500 AU, and finally 1000 AU
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of North Carolina, Chapel Hill
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF) | baseline, 4 hours post-allergen challenge | NELF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge. |
| Mean Change in Eosinophils Per mL in Nasal Lavage Fluid (NLF) | Baseline, 4 hours post-allergen challenge | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Interleukin-31 (IL-31) Concentrations in NELF | Pre- and 4 hours-post nasal allergen challenge | NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge. |
| Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF | baseline, 4 hours post-allergen challenge | NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge. |
| Mean Change in Interleukin-5 (IL-5) Concentrations in NELF | baseline, 4 hours post-allergen challenge | NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge. |
| Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF | baseline, 4 hours post-allergen challenge | NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Nasal Epithelial Cell Messenger Ribonucleic Acid (mRNA) Expression | Baseline, 4 hours post- nasal allergen challenge | 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). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from individuals who completed the general screening process at the Center for Environmental Medicine, Asthma and Lung Biology.
Participants by arm
| Arm | Count |
|---|---|
| Non-smokers Non-smoking adults with a history of dust mite allergy and allergic rhinitis | 8 |
| Cigarette Smokers Cigarette smoking adults with a history of dust mite allergy and allergic rhinitis | 3 |
| E-cig Users E-cig using adults with a history of dust mite allergy and allergic rhinitis | 1 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Run-In | Failed screening allergen challenge | 1 | 0 | 0 |
| Run-In | Loss of funding after informed consent but before screening allergen challenge | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Non-smokers | Cigarette Smokers | E-cig Users | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 3 Participants | 1 Participants | 12 Participants |
| Age, Continuous | 29.6 Years | 34.6 Years | 21.4 Years | 29 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 2 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 1 Participants | 1 Participants | 7 Participants |
| Region of Enrollment United States | 8 Participants | 3 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 4 / 8 | 0 / 3 | 1 / 1 |
| serious Total, serious adverse events | 0 / 8 | 0 / 3 | 0 / 1 |
Outcome results
Primary
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.
Time frame: baseline, 4 hours post-allergen challenge
Population: Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-smokers | Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF) | 31374 micrograms/L | Standard Deviation 37261 |
| Cigarette Smokers | Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF) | -50847 micrograms/L | Standard Deviation 45535 |
| E-cig Users | Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF) | -17851 micrograms/L | Standard Deviation 0 |
Primary
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).
Time frame: Baseline, 4 hours post-allergen challenge
Population: NLF samples obtained from six non-smokers, 3 smokers and 1 e-cig user were contaminated with blood and therefore were not suitable samples for analysis of nasal inflammatory cells. The protocol was changed to include eosinophilic cationic protein (ECP) in nasal epithelial lining fluid (NELF) as the primary outcome measure.
Secondary
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.
Time frame: Pre- and 4 hours-post nasal allergen challenge
Population: Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-smokers | Mean Change in Interleukin-31 (IL-31) Concentrations in NELF | 0.76 picograms/mL | Standard Deviation 1.01 |
| Cigarette Smokers | Mean Change in Interleukin-31 (IL-31) Concentrations in NELF | 0.06 picograms/mL | Standard Deviation 0.28 |
| E-cig Users | Mean Change in Interleukin-31 (IL-31) Concentrations in NELF | 4.76 picograms/mL | Standard Deviation 0 |
Secondary
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.
Time frame: baseline, 4 hours post-allergen challenge
Population: Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-smokers | Mean Change in Interleukin-5 (IL-5) Concentrations in NELF | 75.82 picograms/mL | Standard Deviation 53.02 |
| Cigarette Smokers | Mean Change in Interleukin-5 (IL-5) Concentrations in NELF | 3.42 picograms/mL | Standard Deviation 4.58 |
| E-cig Users | Mean Change in Interleukin-5 (IL-5) Concentrations in NELF | 240.9 picograms/mL | Standard Deviation 0 |
Secondary
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.
Time frame: baseline, 4 hours post-allergen challenge
Population: Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-smokers | Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF | 72.52 picograms/mL | Standard Deviation 42.9 |
| Cigarette Smokers | Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF | 10.04 picograms/mL | Standard Deviation 8.03 |
| E-cig Users | Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF | 91.43 picograms/mL | Standard Deviation 0 |
Secondary
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.
Time frame: baseline, 4 hours post-allergen challenge
Population: Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-smokers | Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF | 370.8 picograms/mL | Standard Deviation 511.6 |
| Cigarette Smokers | Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF | 18.97 picograms/mL | Standard Deviation 12.01 |
| E-cig Users | Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF | 32.98 picograms/mL | Standard Deviation 0 |
Other Pre-specified
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).
Time frame: Baseline, 4 hours post- nasal allergen challenge
Population: No samples were analyzed due to lack of funding and early termination of the study