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

COPD Clinical Trial

Official title:

Airway Inflammatory Profile and Clinical Presentation of COPD: A Comparison Between Never Smokers and Smokers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03274791
• Other study ID #: COPDNS
• Status: Completed
• Phase: N/A
• First received: August 24, 2017
• Last updated: September 6, 2017
• Start date: September 2013
• Est. completion date: January 2017

Study information

• Verified date: September 2017
• Source: Ministry of Scientific Research, Tunisia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: January 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Subjects with COPD, according to GOLD criteria (smokers and never smokers). Moreover, inhaled short-acting ß2-agonists were stopped at least 8h before the test and inhaled long-acting ß2-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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Airway Obstruction
• COPD
• Inflammation

Intervention

Diagnostic Test:
• Analysis of induced sputum
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.
• Lung Function 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.
• Enzyme-linked Immunosorbent Assay
IL-8 and TNF-a 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-a (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-a. The intra assay coefficients of variability were 8.7% for IL-8 and 7.7% for TNF- a.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ministry of Scientific Research, Tunisia

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight measurement	Weight was measured in kilograms for all the participants.	6 months
Primary	Height measurement	Height was measured in meters for all the participants.	6 months
Primary	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
Primary	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
Primary	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	BMI determination	Weight and height values were combined to report BMI in kg/m2	6 months
Secondary	Tiffeneau ratio (FEV1/FVC)	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.	6 months
Secondary	Sputum cell counts	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.	1 month
Secondary	Sputum supernatant analyses	IL-8 and TNF-a sputum supernatant concentrations were measured in the sputum supernatant of the three studied groups using ELISA test.	3 months