Clinical Features and Airways Inflammation in Never Smokers and Smokers With COPD

NCT03274791 | Completed DMC

• 1 other identifier: COPDNS
• Study Type: observational
• Target: 68
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

COPD; Airway Obstruction; Inflammation

Keywords

COPD; smoking; induced sputum; clinical features

Outcome Measures

Primary Outcomes (5)

• Weight measurement

  Weight was measured in kilograms for all the participants.

  6 months

• Height measurement

  Height was measured in meters for all the participants.

  6 months

• Forced vital capacity (FVC)

  FVC was measured using a portable spirometer (Easy One ndd. Medizintechnik; Zurich, Switzerland) according to the American Thoracic Society criteria.

  6 months

• Forced expiratory volume in one second (FEV1)

  FEV1 was measured using a portable spirometer (Easy One ndd. Medizintechnik; Zurich, Switzerland) according to the American Thoracic Society criteria.

  6 months

• Sputum induction and collection

  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.

  6 months

Secondary Outcomes (4)

• BMI determination

  6 months

• Tiffeneau ratio (FEV1/FVC)

  6 months

• Sputum cell counts

  1 month

• Sputum supernatant analyses

  3 months

Study Arms (3)

Healthy subjects

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).

Diagnostic Test: Analysis of induced sputum; Diagnostic Test: Lung Function test; Diagnostic Test: Enzyme-linked Immunosorbent Assay

COPD Never smokers

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).

Diagnostic Test: Analysis of induced sputum; Diagnostic Test: Lung Function test; Diagnostic Test: Enzyme-linked Immunosorbent Assay

COPD Smokers

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).

Diagnostic Test: Analysis of induced sputum; Diagnostic Test: Lung Function test; Diagnostic Test: Enzyme-linked Immunosorbent Assay

Interventions

Analysis of induced sputum DIAGNOSTIC_TEST

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.

COPD Never smokers; COPD Smokers; Healthy subjects

Lung Function test DIAGNOSTIC_TEST

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.

Also known as: spirometry

COPD Never smokers; COPD Smokers; Healthy subjects

Enzyme-linked Immunosorbent Assay DIAGNOSTIC_TEST

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.

Also known as: ELISA

COPD Never smokers; COPD Smokers; Healthy subjects

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients were recruited from the department of physiology and functional explorations of Sousse University Hospital. 40 subjects with COPD, according to GOLD criteria (21 current smokers and 19 never smokers) and 28 healthy control subjects participated to the study.

You may qualify if:

• Subjects with COPD, according to GOLD criteria (smokers and never smokers). Moreover, inhaled short-acting β2-agonists were stopped at least 8h before the test and inhaled long-acting β2-agonist were stopped at least 48h before the test.
• Healthy control subjects : never smokers with normal spirometry and did not have a history of lung disease or chronic respiratory symptoms.

You may not qualify if:

• COPD patients were excluded from the study if they had an exacerbation, a respiratory tract infection or if they used a systemic form of corticosteroid preparation (oral or intravenous injection therapy) or antibiotics within the two months prior to the study entry. Patients with other respiratory disorder like pneumonia, pulmonary emboli, congestive heart failure, lung cancer or tuberculosis were also excluded.

Sponsors & Collaborators

• Ministry of Scientific Research, Tunisia: lead

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Airway Obstruction; Inflammation; Smoking

Interventions

Respiratory Function Tests; Spirometry

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Insufficiency; Respiration Disorders; Behavior

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Zouhair Tabka, MD PhD

  Faculty of Medicine of Sousse

  STUDY DIRECTOR

• Amina Mrizak, MSc

  Faculty of Medicine of Sousse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: September 7, 2017
• Study Start: September 1, 2013
• Primary Completion: August 1, 2016
• Study Completion: January 1, 2017
• Last Updated: September 7, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: The data will become available when the article will be accepted by the editorial board of the journal.