<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03302117</url>
  </required_header>
  <id_info>
    <org_study_id>WSIII</org_study_id>
    <nct_id>NCT03302117</nct_id>
  </id_info>
  <brief_title>Pulmonary and Systemic Effects of Exposure to Wood Smoke</brief_title>
  <official_title>Pulmonary and Systemic Effects of Exposure to Wood Smoke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Umeå University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Umeå University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is study is to assess pulmonary and systemic effects of exposure to wood smoke. Healthy&#xD;
      volunteers will be expose under two different occasion to wood smoke and filtered air under&#xD;
      two separated occasions with an interval of 3 weeks in-between. The aim of this study was to&#xD;
      determine whether exposure to wood smoke from incomplete combustion would elicit airway&#xD;
      inflammation in humans.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Brief Summary This is study is to assess pulmonary and systemic effects of exposure to wood&#xD;
      smoke. Healthy volunteers will be expose under two different occasion to wood smoke and to&#xD;
      filtered air for two hours under two separated occasions with an interval of 3 weeks&#xD;
      in-between. The aim of this study was to determine whether exposure to wood smoke from&#xD;
      incomplete combustion would elicit airway inflammation in humans.&#xD;
&#xD;
      Detailed description Air pollution is associate with increased pulmonary and cardiovascular&#xD;
      mobility and mortality. UNICEF recently published a report highlighting the health effects of&#xD;
      air pollution from a global perspective, with particular focus on pediatrics population.&#xD;
      Overall, air pollution is estimated to cause about 7 million deaths each year in the world,&#xD;
      of which about 600,000 of these apply to children under 5 years (1). Indoor and outdoor air&#xD;
      pollutants are the 3rd and 9th most common cause of death. Nearly 3 billion people are&#xD;
      dependent on biomass for daily needs, Exposure to wood smoke has been linked to elevated&#xD;
      asthma prevalence, increased asthma symptoms in children and adults, as well as higher&#xD;
      hospital admissions due to asthma attacks. The association between long-term indoor wood&#xD;
      smoke exposure and the development and worsening of chronic obstructive pulmonary disease has&#xD;
      been shown to be strong in many epidemiological studies (2,3), and the risk for chronic&#xD;
      obstructive pulmonary disease development has been estimated to be more than doubled for&#xD;
      solid fuel smoke compared with smoke from other types of fuels (4). Exposure to smoke from&#xD;
      combustion of wood and other biomass fuels has also been shown to increase the risk for acute&#xD;
      and chronic lower respiratory tract infections, including pneumonias and tuberculosis. The&#xD;
      aim of the current study was to further characterize the respiratory and systemic effects of&#xD;
      exposure to wood smoke emitted from incomplete soot-rich combustion in a wood stove.&#xD;
&#xD;
      The study will be performed in a randomized, double blind, crossover fashion. Twenty healthy&#xD;
      subjects will be exposed on two occasions, under well-controlled situations, to filtered air&#xD;
      and wood smoke in an exposure chamber at Thermochemical Energy Conversion Laboratory at Umeå&#xD;
      University. The chamber is made of stainless steel, has a volume of a 15.3 m3 and an air&#xD;
      exchange rate of around three times per hour and has been previously described (5). The mean&#xD;
      particle mass concentration of wood smoke will be 450 μg/m3. The exposures will last for two&#xD;
      hours, during which the subject will perform intermittent exercise on a bicycle ergometer,&#xD;
      alternate with rest at 15-minute intervals, to achieve an average minute ventilation of 20&#xD;
      L/min/m2 body surface. During the exposures, symptoms well be recorded according to the&#xD;
      modified Borg scale, as described previously (6). Spirometry and impulse oscillometry system&#xD;
      (IOS) will be used to assess the lung function at baseline and immediately after each&#xD;
      exposure. Bronchoscopy will be performed 6 hours after each exposure. Differential cell&#xD;
      counts and soluble components will be analyzed in peripheral blood sampling at baseline and 6&#xD;
      hours after each exposure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 14, 2017</start_date>
  <completion_date type="Anticipated">February 8, 2018</completion_date>
  <primary_completion_date type="Anticipated">February 8, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Crossover</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Pulmonary inflammation</measure>
    <time_frame>Bronchoscopy will be done 6 hours after each exposure.</time_frame>
    <description>Flexible bronchoscopy will done to obtain bronchoalveolar lavage to assess the inflammatory responses by measurement of cell differential counts and cytokines level.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulmonary cytotoxicity</measure>
    <time_frame>Bronchoscopy will be done 6 hours after each exposure.</time_frame>
    <description>Bronchoalveolar lavage will be examined for signs of cytotoxicity by measurement of cell death and apoptosis markers.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Inflammatory changes in endobronchial biopsies</measure>
    <time_frame>Bronchoscopy will be done 6 hours after each exposure and the processing of the immunohistochemistry method will start immediately after each bronchoscopy</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Systemic inflammatory responses</measure>
    <time_frame>Before and 6 hour after each exposure</time_frame>
    <description>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-α), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and club cell secretory protein 16 (CC16, formerly called clara cell protein 16) using ELISA kits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function test</measure>
    <time_frame>At baseline, immediately after and 6 hours after each exposure</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Pulmonary Inflammation</condition>
  <condition>Cytotoxicity</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Wood smoke exposure</intervention_name>
    <description>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</description>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Bronchoalevolar lavage. Endobronchial biopsies. Peripheral blood sampling.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Twenty healthy volunteers (age 20-40, all never smokers) will included. All subjects&#xD;
        undergo a physical examination, baseline blood count and renal function assessment,&#xD;
        spirometry (FEV1, VC and FEV1/VC) and 12 lead electrocardiogram prior to inclusion. All&#xD;
        must be free of airway infection for at least 6 weeks prior to participation. The study was&#xD;
        approved by the regional ethical review board and performed in accordance with the&#xD;
        declaration of Helsinki. All subjects should give their written informed consent.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers&#xD;
&#xD;
          -  Non-smoker&#xD;
&#xD;
          -  Non-allergic&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diabetes Mellitus&#xD;
&#xD;
          -  Renal failure&#xD;
&#xD;
          -  Ischemic heart disease&#xD;
&#xD;
          -  History of hematological disease&#xD;
&#xD;
          -  Previous smoking.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ala Muala, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department for Public Health and Clinical Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ala Muala, MD, PhD</last_name>
    <phone>+46907851785</phone>
    <email>ala.muala@umu.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Thomas Sandström, MD, PhD</last_name>
    <phone>+46907852516</phone>
    <email>thomas.sandstrom@umu.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department for Public Health and Clinical Medicine</name>
      <address>
        <city>Umeå</city>
        <zip>90187</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ala Muala, MD, PhD</last_name>
      <phone>+467851784</phone>
      <email>ala.muala@umu.se</email>
    </contact>
    <contact_backup>
      <last_name>Thomas Sandström, MD, PhD</last_name>
      <phone>+46907852516</phone>
      <email>thomas.sandstrom@umu.se</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <reference>
    <citation>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. No abstract available.</citation>
    <PMID>28114563</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>21248322</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20139228</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20335290</PMID>
  </reference>
  <reference>
    <citation>Unosson J, Blomberg A, Sandstrom T, Muala A, Boman C, Nystrom 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.</citation>
    <PMID>23742058</PMID>
  </reference>
  <reference>
    <citation>Rudell B, Ledin MC, Hammarstrom U, Stjernberg N, Lundback B, Sandstrom T. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust. Occup Environ Med. 1996 Oct;53(10):658-62. doi: 10.1136/oem.53.10.658.</citation>
    <PMID>8943829</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>October 3, 2017</last_update_submitted>
  <last_update_submitted_qc>October 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Wood smoke</keyword>
  <keyword>Bronchoscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03302117
org study id: WSIII
nct id: NCT03302117
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
observational model: Case-Crossover
time perspective: Prospective
measure: Pulmonary inflammation
time frame: Bronchoscopy will be done 6 hours after each exposure.
description: Flexible bronchoscopy will done to obtain bronchoalveolar lavage to assess the inflammatory responses by measurement of cell differential counts and cytokines level.
measure: Pulmonary cytotoxicity
time frame: Bronchoscopy will be done 6 hours after each exposure.
description: Bronchoalveolar lavage will be examined for signs of cytotoxicity by measurement of cell death and apoptosis markers.
measure: Inflammatory changes in endobronchial biopsies
time frame: Bronchoscopy will be done 6 hours after each exposure and the processing of the immunohistochemistry method will start immediately after each bronchoscopy
description: 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
measure: Systemic inflammatory responses
time frame: Before and 6 hour after each exposure
description: 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-α), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and club cell secretory protein 16 (CC16, formerly called clara cell protein 16) using ELISA kits.
measure: Lung function test
time frame: At baseline, immediately after and 6 hours after each exposure
description: 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).
intervention type: Other
intervention name: Wood smoke exposure
description: 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
Bronchoalevolar lavage. Endobronchial biopsies. Peripheral blood sampling.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ala Muala, MD, PhD
role: Principal Investigator
affiliation: Department for Public Health and Clinical Medicine
last name: Ala Muala, MD, PhD
phone: +46907851785
email: ala.muala@umu.se
last name: Thomas Sandström, MD, PhD
phone: +46907852516
email: thomas.sandstrom@umu.se
facility: 
status: Recruiting
contact: 
contact backup: 
country: Sweden
citation: 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. No abstract available.
PMID: 28114563
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.
PMID: 21248322
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.
PMID: 20139228
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.
PMID: 20335290
citation: Unosson J, Blomberg A, Sandstrom T, Muala A, Boman C, Nystrom 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.
PMID: 23742058
citation: Rudell B, Ledin MC, Hammarstrom U, Stjernberg N, Lundback B, Sandstrom T. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust. Occup Environ Med. 1996 Oct;53(10):658-62. doi: 10.1136/oem.53.10.658.
PMID: 8943829
responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Inflammation
sharing ipd: No