Effects of Inhaled Corticosteroids on Sputum Bacterial Load in COPD

Long-term Effects of Inhaled Corticosteroids (ICS) Treatment on Sputum Bacterial and Viral Loads in Chronic Obstructive Pulmonary Disease (COPD) Patients

Exacerbations are important events in the natural history of chronic obstructive pulmonary disease (COPD). Beside the acute (and prolonged) clinical impact, there is evidence that exacerbations negatively affect the natural history of the disease; e.g. lung function decline is accelerated in patients with frequent exacerbations. Bacteria are considered the most relevant cause of exacerbations, but there is evidence that viral infections are equally contributing.

Either alone or in combination with viruses, airway bacterial load in stable COPD correlates with both the frequency of exacerbations and the decline in lung function.

A long-term clinical trial recently showed that the regular treatment with inhaled corticosteroids (ICS) increases the risk of infectious events such as pneumonia, whereas it reduces the frequency of acute COPD exacerbations in COPD.

In a recent study it was found that airway bacterial load increases over time (1 yr follow up) in stable COPD. In this study, virtually all patients (93%) were treated with ICS.

This study is designed to evaluate whether long-term (1 year) ICS treatment increases viral and/or bacterial load in the sputum of COPD patients.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Salmeterol/Fluticasone combination; Drug: Salmeterol

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy, 44121
    • Research Centre on Asthma and COPD - Department of Clinical and Experimental Medicine - Section of Respiratory Disease - University of Ferrara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sixty stable moderate COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2) requiring regular treatment with long-acting bronchodilators, according to international guidelines.
• GOLD stage 2 COPD patients will be enrolled providing they were steroid-free for the last 4 months

Exclusion Criteria:

• Atopy
• Asthma
• Concomitant lung diseases (e.g. lung cancer)
• Acute infections of the respiratory tree in the previous 3 months including COPD exacerbation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ICS/LABA group; Patients assigned to this arm will take bid 50/500 mcg fluticasone/salmeterol combination	Drug: Salmeterol/Fluticasone combination; Salmeterol/Fluticasone 50/500 mcg 1 inhalation bid
Active Comparator: LABA group; Patients assigned to this arm will take bid 50 mcg salmeterol	Drug: Salmeterol; Salmeterol 50 mcg 1 inhalation bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
comparison between groups of bacterial load in sputum	The primary outcome will measure changes in sputum bacterial load of COPD patients treated with inhaled corticosteroids in combination with long acting beta-2 bronchodilators (ICS/LABA group) compared with COPD treated only with long acting beta-2 bronchodilators (LABA group)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlations between clinical outcomes and sputum viral and/or bacterial load	To evaluate whether sputum viral and/or bacterial load correlate with symptoms and need for rescue medication in stabile COPD.	1 year
Sputum viral and/or bacterial load and exacerbation rate	To evaluate whether changes in sputum viral and/or bacterial load (end of the study vs baseline) correlate with exacerbation rate in COPD patients	1 year
Sputum viral and/or bacterial load and lung function	To evaluate correlations between changes in sputum viral and/or bacterial load and changes in lung function over 1 year.	1 year
Airway inflammation and viral/bacterial load in COPD	To evaluate correlations between sputum inflammatory cell profiles and markers of airway inflammation (interleukin-6) and viral/bacterial load at stable stable conditions in COPD paetints.	1 year

Collaborators and Investigators

• Sponsor: Università degli Studi di Ferrara
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Contoli M, Pauletti A, Rossi MR, Spanevello A, Casolari P, Marcellini A, Forini G, Gnesini G, Marku B, Barnes N, Rizzi A, Curradi G, Caramori G, Morelli P, Papi A. Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD. Eur Respir J. 2017 Oct 5;50(4):1700451. doi: 10.1183/13993003.00451-2017. Print 2017 Oct.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: October 1, 2010
• First Submitted That Met QC Criteria: October 1, 2010
• First Posted (Estimate): October 4, 2010

Study Record Updates

• Last Update Posted (Estimate): April 8, 2016
• Last Update Submitted That Met QC Criteria: April 6, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: COPD; Bacteria; Virus; Inhaled Corticosteroids
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Salmeterol Xinafoate
• Other Study ID Numbers: LTEICSBV01