Pulmonary and Systemic Effects of Exposure to Wood Smoke

Cytotoxicity Clinical Trial

Official title:

Pulmonary and Systemic Effects of Exposure to Wood Smoke

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03302117
• Other study ID #: WSIII
• Status: Recruiting
• Phase: N/A
• First received: September 21, 2017
• Last updated: October 3, 2017
• Start date: June 14, 2017
• Est. completion date: February 8, 2018

Study information

• Verified date: September 2017
• Source: Umeå University
• Contact: Ala Muala, MD, PhD
• Phone: +46907851785
• Email: ala.muala[@]umu.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is study is to assess pulmonary and systemic effects of exposure to wood smoke. Healthy volunteers will be expose under two different occasion to wood smoke and filtered air under two separated occasions with an interval of 3 weeks in-between. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans.

Description:

Brief Summary This is study is to assess pulmonary and systemic effects of exposure to wood smoke. Healthy volunteers will be expose under two different occasion to wood smoke and to filtered air for two hours under two separated occasions with an interval of 3 weeks in-between. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans.

Detailed description Air pollution is associate with increased pulmonary and cardiovascular mobility and mortality. UNICEF recently published a report highlighting the health effects of air pollution from a global perspective, with particular focus on pediatrics population. Overall, air pollution is estimated to cause about 7 million deaths each year in the world, of which about 600,000 of these apply to children under 5 years (1). Indoor and outdoor air pollutants are the 3rd and 9th most common cause of death. Nearly 3 billion people are dependent on biomass for daily needs, Exposure to wood smoke has been linked to elevated asthma prevalence, increased asthma symptoms in children and adults, as well as higher hospital admissions due to asthma attacks. The association between long-term indoor wood smoke exposure and the development and worsening of chronic obstructive pulmonary disease has been shown to be strong in many epidemiological studies (2,3), and the risk for chronic obstructive pulmonary disease development has been estimated to be more than doubled for solid fuel smoke compared with smoke from other types of fuels (4). Exposure to smoke from combustion of wood and other biomass fuels has also been shown to increase the risk for acute and chronic lower respiratory tract infections, including pneumonias and tuberculosis. The aim of the current study was to further characterize the respiratory and systemic effects of exposure to wood smoke emitted from incomplete soot-rich combustion in a wood stove.

The study will be performed in a randomized, double blind, crossover fashion. Twenty healthy subjects will be exposed on two occasions, under well-controlled situations, to filtered air and wood smoke in an exposure chamber at Thermochemical Energy Conversion Laboratory at Umeå University. The chamber is made of stainless steel, has a volume of a 15.3 m3 and an air exchange rate of around three times per hour and has been previously described (5). The mean particle mass concentration of wood smoke will be 450 μg/m3. The exposures will last for two hours, during which the subject will perform intermittent exercise on a bicycle ergometer, alternate with rest at 15-minute intervals, to achieve an average minute ventilation of 20 L/min/m2 body surface. During the exposures, symptoms well be recorded according to the modified Borg scale, as described previously (6). Spirometry and impulse oscillometry system (IOS) will be used to assess the lung function at baseline and immediately after each exposure. Bronchoscopy will be performed 6 hours after each exposure. Differential cell counts and soluble components will be analyzed in peripheral blood sampling at baseline and 6 hours after each exposure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: February 8, 2018
• Est. primary completion date: February 8, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers

• Non-smoker

• Non-allergic

Exclusion Criteria:

• Diabetes Mellitus

• Renal failure

• Ischemic heart disease

• History of hematological disease

• Previous smoking.

Related Conditions & MeSH terms

• Cytotoxicity
• Inflammation
• Pneumonia
• Pulmonary Inflammation

Intervention

Other:
• Wood smoke exposure
Healthy volunteers will exposed to filtered air alternate with wood smoke generated from incomplete wood smoke combustion to assess the local and systemic effect of theses exposures

Locations

Country	Name	City	State
Sweden	Department for Public Health and Clinical Medicine	Umeå

Sponsors (1)

Lead Sponsor	Collaborator
Umeå University

Country where clinical trial is conducted

Sweden, 

References & Publications (6)

Friedrich MJ. UNICEF Reports on the Impact of Air Pollution on Children. JAMA. 2017 Jan 17;317(3):246. doi: 10.1001/jama.2016.19034. — View Citation

Hu G, Zhou Y, Tian J, Yao W, Li J, Li B, Ran P. Risk of COPD from exposure to biomass smoke: a metaanalysis. Chest. 2010 Jul;138(1):20-31. doi: 10.1378/chest.08-2114. Epub 2010 Feb 5. Review. — View Citation

Kurmi OP, Semple S, Simkhada P, Smith WC, Ayres JG. COPD and chronic bronchitis risk of indoor air pollution from solid fuel: a systematic review and meta-analysis. Thorax. 2010 Mar;65(3):221-8. doi: 10.1136/thx.2009.124644. Review. — View Citation

Po JY, FitzGerald JM, Carlsten C. Respiratory disease associated with solid biomass fuel exposure in rural women and children: systematic review and meta-analysis. Thorax. 2011 Mar;66(3):232-9. doi: 10.1136/thx.2010.147884. Epub 2011 Jan 19. Review. — View Citation

Rudell B, Ledin MC, Hammarström U, Stjernberg N, Lundbäck B, Sandström T. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust. Occup Environ Med. 1996 Oct;53(10):658-62. — View Citation

Unosson J, Blomberg A, Sandström T, Muala A, Boman C, Nyström R, Westerholm R, Mills NL, Newby DE, Langrish JP, Bosson JA. Exposure to wood smoke increases arterial stiffness and decreases heart rate variability in humans. Part Fibre Toxicol. 2013 Jun 6;10:20. doi: 10.1186/1743-8977-10-20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary inflammation	Flexible bronchoscopy will done to obtain bronchoalveolar lavage to assess the inflammatory responses by measurement of cell differential counts and cytokines level.	Bronchoscopy will be done 6 hours after each exposure.
Primary	Pulmonary cytotoxicity	Bronchoalveolar lavage will be examined for signs of cytotoxicity by measurement of cell death and apoptosis markers.	Bronchoscopy will be done 6 hours after each exposure.
Primary	Inflammatory changes in endobronchial biopsies	Endobronchial biopsies will be obtained by using flexible bronchoscopy. The biopsies will be stained by using immunohistochemistry method for assessing the inflammatory responses after each exposures	Bronchoscopy will be done 6 hours after each exposure and the processing of the immunohistochemistry method will start immediately after each bronchoscopy
Secondary	Systemic inflammatory responses	Peripheral blood samples will be centrifuged at 3,000xg for 30 min at 4 Celsius and then plasma will be removed and frozen at -80 Celsius for further analysis. Plasma samples will be analysed for markers of acute inflammation: Interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-a), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and club cell secretory protein 16 (CC16, formerly called clara cell protein 16) using ELISA kits.	Before and 6 hour after each exposure
Secondary	Lung function test	Assessment of lung function by using using a spirometer (Jaeger spirometer, Germany). The tests were performed according to the guidelines of the American Thoracic Society. An new method will used here also by using impulse oscillometry system (IOS).	At baseline, immediately after and 6 hours after each exposure