Woodsmoke Particulate + Hypertonic Saline

NCT03851406 | Completed Results DMC FDA Device

• 1 other identifier: 18-1895
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Deployment of military personnel has been associated with increased respiratory illness likely due, in part, to inhalation of unusual particulate matter (PM), such as from burn pits. Inflammation is a key initial response to inhaled particulates. The investigator has developed a protocol using inhaled wood smoke particles (WSP) as a way to study PM-induced airway inflammation. Exposure to wood smoke particles causes symptoms, even in healthy people, such as eye irritation, cough, shortness of breath, and increased mucous production. The purpose of this research study is to see if a single treatment of inhaled hypertonic saline (HS) can diminish this PM-induced airway inflammation by rapidly clearing the WSP inhaled particles from airway surfaces. The exposure will be 500 ug/m³ of WSP for 2 hours, with intermittent exercise on a bicycle and rest. The wood is burned in a typical wood stove and piped into the chamber.

Conditions

Airway Inflammation

Outcome Measures

Primary Outcomes (2)

• Change From Baseline to 4 Hours in Sputum Percent Neutrophils

  Change in sputum percent neutrophils from baseline to 4 hours post WSP exposure

  Baseline, 4 hours post WSP exposure

• Change From Baseline to 24 Hours in Sputum Percent Neutrophils

  Change in sputum percent neutrophils from baseline to 24 hours post WSP exposure

  Baseline, 24 hours post WSP exposure

Secondary Outcomes (7)

• Change in Number of Sputum Neutrophils

  Baseline, 4 and 24 hours post WSP exposure

• Change in Number of Sputum Eosinophils

  Baseline, 4 and 24 hours post WSP exposure

• Change in Percent Sputum Eosinophils

  Baseline, 4 and 24 hours post WSP exposure

• Change in Interleukin-1b

  Baseline, 4 and 24 hours post WSP exposure

• Change in Interleukin-6

  Baseline, 4 and 24 hours post WSP exposure

Other Outcomes (1)

• Mucociliary Clearance (MCC)

  4 hours post WSP exposure]

Study Arms (2)

5% Hypertonic Saline, then No Inhaled Treatment

ACTIVE COMPARATOR

Participants will receive 5% Hypertonic Saline following WSP exposure. After a 2-week washout period, participants will receive no treatment following WSP exposure.

Device: 5% Hypertonic Saline; Other: No treatment

No Inhaled Treatment, then 5% Hypertonic Saline

ACTIVE COMPARATOR

Participants will receive no inhaled treatment following WSP exposure. After a 2-week washout period, participants will receive 5% Hypertonic Saline following WSP exposure.

Device: 5% Hypertonic Saline; Other: No treatment

Interventions

5% Hypertonic Saline DEVICE

Immediately following exit from the wood smoke chamber, participants will inhale 15 mL of 5% Hypertonic Saline for 15 minutes delivered by Pari neb with a coached cough maneuver.

5% Hypertonic Saline, then No Inhaled Treatment; No Inhaled Treatment, then 5% Hypertonic Saline

No treatment OTHER

No inhaled treatment will be provided immediately following exit from the wood smoke chamber.

5% Hypertonic Saline, then No Inhaled Treatment; No Inhaled Treatment, then 5% Hypertonic Saline

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 years, inclusive, of both genders
• Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy
• No history of episodic wheezing, chest tightness, or shortness of breath consistent with asthma, or physician-diagnosed asthma.
• forced expiratory volume at one second (FEV1) of at least 80% of predicted and FEV1/forced vital capacity (FVC) ratio of \>0.70.
• Oxygen saturation of \>93%
• Ability to provide an induced sputum sample.
• Subject must demonstrate a \>10% increase in sputum %PMNs 6 hours following inhaled WSP exposure, when compared to baseline sputum (to be completed in a separate protocol #15-1775).

You may not qualify if:

• Clinical contraindications:
• Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, history of chronic infections/immunodeficiency.
• Viral upper respiratory tract infection within 4 weeks of challenge.
• Any acute infection requiring antibiotics within 4 weeks of exposure or fever of unknown origin within 4 weeks of challenge.
• Abnormal physical findings at the baseline visit, including but not limited to abnormalities on auscultation, temperature of 37.8° C, Systolic BP \> 150mm Hg or \< 85 mm Hg; or Diastolic BP \> 90 mm Hg or \< 50 mm Hg, or pulse oximetry saturation reading less than 93%.
• Physician diagnosis of asthma
• If there is a history of allergic rhinitis, subjects must be asymptomatic of allergic rhinitis at the time of study enrollment.
• Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
• Medications which may impact the results of the WSP exposure, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents)
• Cigarette smoking \> 1 pack per month
• Unwillingness to use reliable contraception if sexually active (IUD, birth control pills/patch, condoms).
• Use of immunosuppressive or anticoagulant medications including routine use of NSAIDS. Oral contraceptives are acceptable, as are antidepressants and other medications may be permitted if, in the opinion of the investigator, the medication will not interfere with the study procedures or compromise safety and if the dosage has been stable for 1 month.
• Orthopedic injuries or impediments that would preclude bicycle or treadmill exercise.
• Inability to avoid NSAIDS, Multivitamins, Vitamin C or E or herbal supplements.
• Allergy/sensitivity to study drugs or their formulations

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• United States Department of Defense: collaborator

Study Sites (1)

Center for Environmental Medicine, Asthma and Lung Biology at UNC Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (23)

• Pugh MJ, Jaramillo CA, Leung KW, Faverio P, Fleming N, Mortensen E, Amuan ME, Wang CP, Eapen B, Restrepo M, Morris MJ. Increasing Prevalence of Chronic Lung Disease in Veterans of the Wars in Iraq and Afghanistan. Mil Med. 2016 May;181(5):476-81. doi: 10.7205/MILMED-D-15-00035.

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• Korzeniewski K, Nitsch-Osuch A, Konior M, Lass A. Respiratory tract infections in the military environment. Respir Physiol Neurobiol. 2015 Apr;209:76-80. doi: 10.1016/j.resp.2014.09.016. Epub 2014 Sep 30.

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• Baird CP. Review of the Institute of Medicine report: long-term health consequences of exposure to burn pits in Iraq and Afghanistan. US Army Med Dep J. 2012 Jul-Sep:43-7. No abstract available.

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• Gomez JC, Yamada M, Martin JR, Dang H, Brickey WJ, Bergmeier W, Dinauer MC, Doerschuk CM. Mechanisms of interferon-gamma production by neutrophils and its function during Streptococcus pneumoniae pneumonia. Am J Respir Cell Mol Biol. 2015 Mar;52(3):349-64. doi: 10.1165/rcmb.2013-0316OC.

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• Barth SK, Dursa EK, Bossarte R, Schneiderman A. Lifetime Prevalence of Respiratory Diseases and Exposures Among Veterans of Operation Enduring Freedom and Operation Iraqi Freedom Veterans: Results From the National Health Study for a New Generation of U.S. Veterans. J Occup Environ Med. 2016 Dec;58(12):1175-1180. doi: 10.1097/JOM.0000000000000885.

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• Szema AM. Occupational Lung Diseases among Soldiers Deployed to Iraq and Afghanistan. Occup Med Health Aff. 2013;1:10.4172/2329-6879.1000117. doi: 10.4172/2329-6879.1000117.

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• Auerbach A, Hernandez ML. The effect of environmental oxidative stress on airway inflammation. Curr Opin Allergy Clin Immunol. 2012 Apr;12(2):133-9. doi: 10.1097/ACI.0b013e32835113d6.

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• Alexis NE, Brickey WJ, Lay JC, Wang Y, Roubey RA, Ting JP, Peden DB. Development of an inhaled endotoxin challenge protocol for characterizing evoked cell surface phenotype and genomic responses of airway cells in allergic individuals. Ann Allergy Asthma Immunol. 2008 Mar;100(3):206-15. doi: 10.1016/S1081-1206(10)60444-9.

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• Hernandez ML, Harris B, Lay JC, Bromberg PA, Diaz-Sanchez D, Devlin RB, Kleeberger SR, Alexis NE, Peden DB. Comparative airway inflammatory response of normal volunteers to ozone and lipopolysaccharide challenge. Inhal Toxicol. 2010 Jul;22(8):648-56. doi: 10.3109/08958371003610966.

  PMID: 20540623 BACKGROUND

• Hernandez M, Brickey WJ, Alexis NE, Fry RC, Rager JE, Zhou B, Ting JP, Zhou H, Peden DB. Airway cells from atopic asthmatic patients exposed to ozone display an enhanced innate immune gene profile. J Allergy Clin Immunol. 2012 Jan;129(1):259-61.e1-2. doi: 10.1016/j.jaci.2011.11.007.

  PMID: 22196529 BACKGROUND

• Alexis NE, Peden DB. Blunting airway eosinophilic inflammation results in a decreased airway neutrophil response to inhaled LPS in patients with atopic asthma: a role for CD14. J Allergy Clin Immunol. 2001 Oct;108(4):577-80. doi: 10.1067/mai.2001.118511.

  PMID: 11590384 BACKGROUND

• Hernandez ML, Mills K, Almond M, Todoric K, Aleman MM, Zhang H, Zhou H, Peden DB. IL-1 receptor antagonist reduces endotoxin-induced airway inflammation in healthy volunteers. J Allergy Clin Immunol. 2015 Feb;135(2):379-85. doi: 10.1016/j.jaci.2014.07.039. Epub 2014 Sep 5.

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• Hernandez ML, Wagner JG, Kala A, Mills K, Wells HB, Alexis NE, Lay JC, Jiang Q, Zhang H, Zhou H, Peden DB. Vitamin E, gamma-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers. Free Radic Biol Med. 2013 Jul;60:56-62. doi: 10.1016/j.freeradbiomed.2013.02.001. Epub 2013 Feb 9.

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• Burbank AJ, Duran CG, Pan Y, Burns P, Jones S, Jiang Q, Yang C, Jenkins S, Wells H, Alexis N, Kesimer M, Bennett WD, Zhou H, Peden DB, Hernandez ML. Gamma tocopherol-enriched supplement reduces sputum eosinophilia and endotoxin-induced sputum neutrophilia in volunteers with asthma. J Allergy Clin Immunol. 2018 Apr;141(4):1231-1238.e1. doi: 10.1016/j.jaci.2017.06.029. Epub 2017 Jul 20.

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• Alexis NE, Hu SC, Zeman K, Alter T, Bennett WD. Induced sputum derives from the central airways: confirmation using a radiolabeled aerosol bolus delivery technique. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1964-70. doi: 10.1164/ajrccm.164.10.2104051.

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• Alexis NE, Lay JC, Zeman KL, Geiser M, Kapp N, Bennett WD. In vivo particle uptake by airway macrophages in healthy volunteers. Am J Respir Cell Mol Biol. 2006 Mar;34(3):305-13. doi: 10.1165/rcmb.2005-0373OC. Epub 2005 Nov 4.

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• Sood N, Bennett WD, Zeman K, Brown J, Foy C, Boucher RC, Knowles MR. Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects. Am J Respir Crit Care Med. 2003 Jan 15;167(2):158-63. doi: 10.1164/rccm.200204-293OC. Epub 2002 Oct 31.

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  PMID: 28095128 BACKGROUND

• Ghio AJ, Soukup JM, Case M, Dailey LA, Richards J, Berntsen J, Devlin RB, Stone S, Rappold A. Exposure to wood smoke particles produces inflammation in healthy volunteers. Occup Environ Med. 2012 Mar;69(3):170-5. doi: 10.1136/oem.2011.065276. Epub 2011 Jun 30.

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• Jones B, and Kenward, M.G. . Design and analysis of cross-over trials. Third ed: CRC Press; 2015.

  BACKGROUND

• Alexis NE, Zhou H, Lay JC, Harris B, Hernandez ML, Lu TS, Bromberg PA, Diaz-Sanchez D, Devlin RB, Kleeberger SR, Peden DB. The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in human subjects. J Allergy Clin Immunol. 2009 Dec;124(6):1222-1228.e5. doi: 10.1016/j.jaci.2009.07.036.

  PMID: 19796798 BACKGROUND

Results Point of Contact

• Title: Terry Noah, MD
• Organization: University of North Carolina at Chapel Hill

terry_noah@med.unc.edu

919-966-1055

Study Officials

• Terry Noah, M.D

  UNC Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: To determine the efficacy of nebulized 5% hypertonic saline (HS) (v. no treatment) in mitigating wood smoke particulate (WSP)-induced neutrophilic airway inflammation, assessed via sputum %polymorphonuclear leukocytes (PMNs), in healthy adults 4 hours post WSP exposure.

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: February 22, 2019
• Study Start: August 1, 2019
• Primary Completion: September 12, 2024
• Study Completion: September 12, 2024
• Last Updated: August 8, 2025
• Results First Posted: August 8, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)