<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/NCT03274791</url>
  </required_header>
  <id_info>
    <org_study_id>COPDNS</org_study_id>
    <nct_id>NCT03274791</nct_id>
  </id_info>
  <brief_title>Clinical Features and Airways Inflammation in Never Smokers and Smokers With COPD</brief_title>
  <official_title>Airway Inflammatory Profile and Clinical Presentation of COPD: A Comparison Between Never Smokers and Smokers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ministry of Scientific Research, Tunisia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ministry of Scientific Research, Tunisia</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The aim of this study was to investigate the airway inflammatory profile and the clinical&#xD;
      presentation of chronic obstructive pulmonary disease (COPD) in never smokers compared to&#xD;
      smokers with COPD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      40 COPD patients (21 smokers and 19 never smokers) and 28 healthy never smokers were included&#xD;
      in the present study. Information about respiratory symptoms and comorbidities were&#xD;
      collected. Subjects underwent pulmonary function tests and COPD was defined according to&#xD;
      Global Initiative for Chronic Obstructive lung Disease spirometric criteria. Induced sputum&#xD;
      was collected to determine total and differential inflammatory cells counts as well as&#xD;
      inflammatory mediators (Interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α)). The&#xD;
      Mann-Whitney U and the χ2 tests were used for results comparisons. Correlations between&#xD;
      symptoms, spirometric parameters, cytokines levels, inflammatory cells and risk factors of&#xD;
      COPD were examined with Spearman's rank correlation test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2013</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">August 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Weight measurement</measure>
    <time_frame>6 months</time_frame>
    <description>Weight was measured in kilograms for all the participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Height measurement</measure>
    <time_frame>6 months</time_frame>
    <description>Height was measured in meters for all the participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Forced vital capacity (FVC)</measure>
    <time_frame>6 months</time_frame>
    <description>FVC was measured using a portable spirometer (Easy One ndd. Medizintechnik; Zurich, Switzerland) according to the American Thoracic Society criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Forced expiratory volume in one second (FEV1)</measure>
    <time_frame>6 months</time_frame>
    <description>FEV1 was measured using a portable spirometer (Easy One ndd. Medizintechnik; Zurich, Switzerland) according to the American Thoracic Society criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sputum induction and collection</measure>
    <time_frame>6 months</time_frame>
    <description>Sputum induction was conducted by inhalation of nebulised sterile hypertonic saline solution followed by coughing and expectoration of airway secretions. For nebulisation, an ultrasound nebulizer was used for 5-20 min to provide an adequate amount of sample. The subject is asked to cough and expectorate at 5 min intervals.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>BMI determination</measure>
    <time_frame>6 months</time_frame>
    <description>Weight and height values were combined to report BMI in kg/m2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tiffeneau ratio (FEV1/FVC)</measure>
    <time_frame>6 months</time_frame>
    <description>The calculation of FEV1/FVC allows the identification of obstructive ventilatory defect. A FEV1/FVC &lt; 70 % where FEV1 is reduced more than FVC signifies an obstructive defect.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sputum cell counts</measure>
    <time_frame>1 month</time_frame>
    <description>Four hundred non-squamous cells were counted by two technicians and the mean of the two scores was expressed as percentage of the total cell count. Sputum samples containing &gt;20% of squamous cells and/or with cell viability &lt;70% were excluded from analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sputum supernatant analyses</measure>
    <time_frame>3 months</time_frame>
    <description>IL-8 and TNF-α sputum supernatant concentrations were measured in the sputum supernatant of the three studied groups using ELISA test.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">68</enrollment>
  <condition>COPD</condition>
  <condition>Airway Obstruction</condition>
  <condition>Inflammation</condition>
  <arm_group>
    <arm_group_label>Healthy subjects</arm_group_label>
    <description>Healthy non-smoking subjects were never smokers with normal spirometry and did not have a history of lung disease or chronic respiratory symptoms.&#xD;
Information about respiratory symptoms and comorbidities were collected. Healthy subjects underwent pulmonary function tests (Spirometry). Induced sputum was collected to determine total and differential inflammatory cells counts as well as inflammatory mediators (Interleukin-8 and tumor necrosis factor-alpha).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>COPD Never smokers</arm_group_label>
    <description>Never smokers referred to subjects who had never smoked Airflow limitation in COPD was defined as a post-bronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio &lt;70% and FEV1 reversibility of &lt;12% and 200 mL from baseline values after inhalation of 400 µg of Salbutamol.&#xD;
Information about respiratory symptoms and comorbidities were collected. Never smoking subjects with COPD underwent pulmonary function tests (Spirometry). Induced sputum was collected to determine total and differential inflammatory cells counts as well as inflammatory mediators (Interleukin-8 and tumor necrosis factor-alpha).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>COPD Smokers</arm_group_label>
    <description>Smokers were defined as persons who had smoked &gt; 20 packs of cigarettes in a lifetime and who continue smoking every day.&#xD;
Airflow limitation in COPD was defined as a post-bronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio &lt;70% and FEV1 reversibility of &lt;12% and 200 mL from baseline values after inhalation of 400 µg of Salbutamol.&#xD;
Information about respiratory symptoms and comorbidities were collected. Smoking subjects with COPD underwent pulmonary function tests (Spirometry). Induced sputum was collected to determine total and differential inflammatory cells counts as well as inflammatory mediators (Interleukin-8 and tumor necrosis factor-alpha).</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Analysis of induced sputum</intervention_name>
    <description>Induced sputum was collected and analysed in the three arms (Healthy subjects, Never smokers with COPD and smokers with COPD) The volume of the sputum sample, was treated with an equal volume of 0.1% dithiothreitol. The samples were then vortexed and placed in a shaking water bath at 37°C for 15 min to ensure complete homogeneisation. The suspensions were centrifuged at 400× g and the sputum supernatant stored at -80°C until cytokines analysis. The cell pellet was resuspended in 0.5% bovine serum albumin in phosphate buffered saline and cytospin were made by putting 100 µL of the cell suspension in the funnels.&#xD;
Slides for differential cell counts were stained with May-Grünwald Giemsa.</description>
    <arm_group_label>COPD Never smokers</arm_group_label>
    <arm_group_label>COPD Smokers</arm_group_label>
    <arm_group_label>Healthy subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Lung Function test</intervention_name>
    <description>All the subjects underwent pulmonary function tests (Healthy subjects, Never smokers with COPD and smokers with COPD).&#xD;
Pulmonary function parameters were measured using a portable spirometer (Easy One ndd. Medizintechnik; Zurich, Switzerland) according to the ATS criteria (American Thoracic Society). Reversibility test was performed 15 min after inhalation of 400 µg of Salbutamol (Ventolin, GlaxoSmithKline, Middlesex, UK). All spirometry data were graded for quality and only tests that met high quality scores were used for the final analysis.</description>
    <arm_group_label>COPD Never smokers</arm_group_label>
    <arm_group_label>COPD Smokers</arm_group_label>
    <arm_group_label>Healthy subjects</arm_group_label>
    <other_name>spirometry</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Enzyme-linked Immunosorbent Assay</intervention_name>
    <description>IL-8 and TNF-α were measured in the sputum supernatant of all the subjects (Healthy subjects, Never smokers with COPD and smokers with COPD).&#xD;
Commercially available kits were used to detect IL-8 (Human IL-8 Immuno-Biological Laboratories ELISA Kit) and TNF-α (Human TNF-alpha Sigma-Aldrich ELISA Kit) concentrations in the sputum supernatants. The absorbance was measured at 450 nm. The lower limits detection were 2 pg/mL for IL-8 and 5 pg/mL for TNF-α. The intra assay coefficients of variability were 8.7% for IL-8 and 7.7% for TNF- α.</description>
    <arm_group_label>COPD Never smokers</arm_group_label>
    <arm_group_label>COPD Smokers</arm_group_label>
    <arm_group_label>Healthy subjects</arm_group_label>
    <other_name>ELISA</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients were recruited from the department of physiology and functional explorations of&#xD;
        Sousse University Hospital. 40 subjects with COPD, according to GOLD criteria (21 current&#xD;
        smokers and 19 never smokers) and 28 healthy control subjects participated to the study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with COPD, according to GOLD criteria (smokers and never smokers). Moreover,&#xD;
             inhaled short-acting β2-agonists were stopped at least 8h before the test and inhaled&#xD;
             long-acting β2-agonist were stopped at least 48h before the test.&#xD;
&#xD;
          -  Healthy control subjects : never smokers with normal spirometry and did not have a&#xD;
             history of lung disease or chronic respiratory symptoms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  COPD patients were excluded from the study if they had an exacerbation, a respiratory&#xD;
             tract infection or if they used a systemic form of corticosteroid preparation (oral or&#xD;
             intravenous injection therapy) or antibiotics within the two months prior to the study&#xD;
             entry. Patients with other respiratory disorder like pneumonia, pulmonary emboli,&#xD;
             congestive heart failure, lung cancer or tuberculosis were also excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zouhair Tabka, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>Faculty of Medicine of Sousse</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Amina Mrizak, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Faculty of Medicine of Sousse</affiliation>
  </overall_official>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>September 6, 2017</last_update_submitted>
  <last_update_submitted_qc>September 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ministry of Scientific Research, Tunisia</investigator_affiliation>
    <investigator_full_name>Myriam Denguezli</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>smoking</keyword>
  <keyword>induced sputum</keyword>
  <keyword>clinical features</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Airway Obstruction</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD that underlie results will be shared in a publication</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>The data will become available when the article will be accepted by the editorial board of the journal.</ipd_time_frame>
  </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/NCT03274791
org study id: COPDNS
nct id: NCT03274791
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study was to investigate the airway inflammatory profile and the clinical
      presentation of chronic obstructive pulmonary disease (COPD) in never smokers compared to
      smokers with COPD.
40 COPD patients (21 smokers and 19 never smokers) and 28 healthy never smokers were included
      in the present study. Information about respiratory symptoms and comorbidities were
      collected. Subjects underwent pulmonary function tests and COPD was defined according to
      Global Initiative for Chronic Obstructive lung Disease spirometric criteria. Induced sputum
      was collected to determine total and differential inflammatory cells counts as well as
      inflammatory mediators (Interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α)). The
      Mann-Whitney U and the χ2 tests were used for results comparisons. Correlations between
      symptoms, spirometric parameters, cytokines levels, inflammatory cells and risk factors of
      COPD were examined with Spearman's rank correlation test.
observational model: Case-Control
time perspective: Retrospective
measure: Weight measurement
time frame: 6 months
description: Weight was measured in kilograms for all the participants.
measure: Height measurement
time frame: 6 months
description: Height was measured in meters for all the participants.
measure: Forced vital capacity (FVC)
time frame: 6 months
description: FVC was measured using a portable spirometer (Easy One ndd. Medizintechnik; Zurich, Switzerland) according to the American Thoracic Society criteria.
measure: Forced expiratory volume in one second (FEV1)
time frame: 6 months
description: FEV1 was measured using a portable spirometer (Easy One ndd. Medizintechnik; Zurich, Switzerland) according to the American Thoracic Society criteria.
measure: Sputum induction and collection
time frame: 6 months
description: Sputum induction was conducted by inhalation of nebulised sterile hypertonic saline solution followed by coughing and expectoration of airway secretions. For nebulisation, an ultrasound nebulizer was used for 5-20 min to provide an adequate amount of sample. The subject is asked to cough and expectorate at 5 min intervals.
measure: BMI determination
time frame: 6 months
description: Weight and height values were combined to report BMI in kg/m2
measure: Tiffeneau ratio (FEV1/FVC)
time frame: 6 months
description: The calculation of FEV1/FVC allows the identification of obstructive ventilatory defect. A FEV1/FVC < 70 % where FEV1 is reduced more than FVC signifies an obstructive defect.
measure: Sputum cell counts
time frame: 1 month
description: Four hundred non-squamous cells were counted by two technicians and the mean of the two scores was expressed as percentage of the total cell count. Sputum samples containing >20% of squamous cells and/or with cell viability <70% were excluded from analysis.
measure: Sputum supernatant analyses
time frame: 3 months
description: IL-8 and TNF-α sputum supernatant concentrations were measured in the sputum supernatant of the three studied groups using ELISA test.
arm group label: Healthy subjects
description: Healthy non-smoking subjects were never smokers with normal spirometry and did not have a history of lung disease or chronic respiratory symptoms.
Information about respiratory symptoms and comorbidities were collected. Healthy subjects underwent pulmonary function tests (Spirometry). Induced sputum was collected to determine total and differential inflammatory cells counts as well as inflammatory mediators (Interleukin-8 and tumor necrosis factor-alpha).
arm group label: COPD Never smokers
description: Never smokers referred to subjects who had never smoked Airflow limitation in COPD was defined as a post-bronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio <70% and FEV1 reversibility of <12% and 200 mL from baseline values after inhalation of 400 µg of Salbutamol.
Information about respiratory symptoms and comorbidities were collected. Never smoking subjects with COPD underwent pulmonary function tests (Spirometry). Induced sputum was collected to determine total and differential inflammatory cells counts as well as inflammatory mediators (Interleukin-8 and tumor necrosis factor-alpha).
arm group label: COPD Smokers
description: Smokers were defined as persons who had smoked > 20 packs of cigarettes in a lifetime and who continue smoking every day.
Airflow limitation in COPD was defined as a post-bronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio <70% and FEV1 reversibility of <12% and 200 mL from baseline values after inhalation of 400 µg of Salbutamol.
Information about respiratory symptoms and comorbidities were collected. Smoking subjects with COPD underwent pulmonary function tests (Spirometry). Induced sputum was collected to determine total and differential inflammatory cells counts as well as inflammatory mediators (Interleukin-8 and tumor necrosis factor-alpha).
intervention type: Diagnostic Test
intervention name: Analysis of induced sputum
description: Induced sputum was collected and analysed in the three arms (Healthy subjects, Never smokers with COPD and smokers with COPD) The volume of the sputum sample, was treated with an equal volume of 0.1% dithiothreitol. The samples were then vortexed and placed in a shaking water bath at 37°C for 15 min to ensure complete homogeneisation. The suspensions were centrifuged at 400× g and the sputum supernatant stored at -80°C until cytokines analysis. The cell pellet was resuspended in 0.5% bovine serum albumin in phosphate buffered saline and cytospin were made by putting 100 µL of the cell suspension in the funnels.
Slides for differential cell counts were stained with May-Grünwald Giemsa.
arm group label: COPD Never smokers
arm group label: COPD Smokers
arm group label: Healthy subjects
intervention type: Diagnostic Test
intervention name: Lung Function test
description: All the subjects underwent pulmonary function tests (Healthy subjects, Never smokers with COPD and smokers with COPD).
Pulmonary function parameters were measured using a portable spirometer (Easy One ndd. Medizintechnik; Zurich, Switzerland) according to the ATS criteria (American Thoracic Society). Reversibility test was performed 15 min after inhalation of 400 µg of Salbutamol (Ventolin, GlaxoSmithKline, Middlesex, UK). All spirometry data were graded for quality and only tests that met high quality scores were used for the final analysis.
arm group label: COPD Never smokers
arm group label: COPD Smokers
arm group label: Healthy subjects
other name: spirometry
intervention type: Diagnostic Test
intervention name: Enzyme-linked Immunosorbent Assay
description: IL-8 and TNF-α were measured in the sputum supernatant of all the subjects (Healthy subjects, Never smokers with COPD and smokers with COPD).
Commercially available kits were used to detect IL-8 (Human IL-8 Immuno-Biological Laboratories ELISA Kit) and TNF-α (Human TNF-alpha Sigma-Aldrich ELISA Kit) concentrations in the sputum supernatants. The absorbance was measured at 450 nm. The lower limits detection were 2 pg/mL for IL-8 and 5 pg/mL for TNF-α. The intra assay coefficients of variability were 8.7% for IL-8 and 7.7% for TNF- α.
arm group label: COPD Never smokers
arm group label: COPD Smokers
arm group label: Healthy subjects
other name: ELISA
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Zouhair Tabka, MD PhD
role: Study Director
affiliation: Faculty of Medicine of Sousse
last name: Amina Mrizak, MSc
role: Principal Investigator
affiliation: Faculty of Medicine of Sousse
responsible party type: Principal Investigator
investigator affiliation: Ministry of Scientific Research, Tunisia
investigator full name: Myriam Denguezli
investigator title: Assistant Professor
mesh term: Airway Obstruction
mesh term: Inflammation
sharing ipd: Yes
ipd description: All IPD that underlie results will be shared in a publication
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd time frame: The data will become available when the article will be accepted by the editorial board of the journal.