Detection of Aspergillus Fumigatus and Sensitization in COPD Patients With Bronchiectasis vs Without Bronchiectasis

Detection of Aspergillus Fumigatus and Sensitization in COPD Patients With Bronchiectasis vs COPD Patients Without Bronchiectasis

A single center case-control study with 100 COPD patients will be organized to compare patients with and without bronchiectasis with regard to the presence of Aspergillus in sputum samples, Aspergillus sensitization and vitamin D. Induced sputum samples will be optimized for culture, Aspergillus galatomannan analysis and RT-PCR.

This study is part of a larger project in which we assume that chronic respiratory infection by Aspergillus fumigatus and the accompanying immune response play an important role in the development of bronchiectasis in COPD. We suspect that this mechanism is controlled by vitamin D and it fails by suppression of the vitamin D receptor by Aspergillus fumigatus.

The present study is designed by the Laboratory of pneumology and will be conducted in collaboration with the Laboratory of clinical bacteriology and mycology of the Catholic University of Leuven.

Study Overview

• Status: Unknown
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Procedure: Sputum induction; Procedure: Skin prick test; Other: Questionnaires

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Belgium
  • Vlaanderen
    • Leuven, Vlaanderen, Belgium, 3000
      • Recruiting
      • Uz Gasthuisberg
      • Contact: Stephanie Everaerts, MD.; Phone Number: 0032 016 37 94 92; Email: Stephanie.Everaerts@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who present in the emergency department with an acute COPD exacerbation (as defined by GOLD executive summary) requiring hospitalization are eligible for this study. Patients should have an established diagnosis of COPD (based on clinical history or pulmonary function test). They will be recruited during their hospital stay in the University Hospital of Leuven.

Additionally, we will include 20 patients with COPD (10 with bronchiectasis versus 10 without) in stable state during their outpatient visits.

Description

Inclusion Criteria:

• Established diagnosis of COPD by medical doctor (based on clinical history or pulmonary function test)
• Smoking history of at least 10 pack-years
• CT Thorax available for assessment of bronchiectasis
• FEV1 >= 30%

Exclusion Criteria:

• Mechanical or non-invasive ventilation
• Other main respiratory diagnosis other than COPD
• Active mycobacterial disease
• Immunosuppression other than steroids
• Active cancer treatment

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COPD patients with bronchiectasis; All patients will receive standard therapy for AECOPD. Additional for this study are: Sputum induction, Skin prick test, Questionnaires	Procedure: Sputum induction; Patients will have to puff 200µg of salbutamol (metered-dose inhaler with spacer device). After 10 minutes FEV1 will be measured with MIR spirobank. If FEV1 is >= 30% we can safely proceed with sputum induction. An ultrasonic nebulizer will be used to induce sputum. 4% sodiumchloride will be inhaled. Induction will be performed at 5-min intervals until a sample of good quality is obtained. Sodiumchloride of 5% will be used if no good sample is obtained after two intervals with the 4% solution. Maximal time of induction will be 20 minutes. Subjects will spit saliva into one container and rinse the mouth thoroughly with water before coughing sputum into another sterile container. Samples will be refrigerated at 4°C and processed within 24 hours of collection.; Procedure: Skin prick test; Skin Prick Test is a reliable method to diagnose IgE-mediated allergic disease. It is minimally invasive and results are immediately available. Interpretation utilizes the presence and degree of cutaneous reactivity as a surrogate marker for sensitization. A positive control, a negative control and Aspergillus fumigatus will be tested. Location will be Protocol version 1 3/11/2014 marked on the volar aspect of the forearm and drops of each solution will be placed (>= 2cm between drops). A single-head metal lancet will be pressed through the drop of allergen extract and held against the skin for at least 1 second. A new lancet will be utilized for each drop. A wheal diameter of >= 3mm is a positive result.; Other: Questionnaires; MRC: Medical Research Council Scale CAT: COPD Assessment Test SGRQ: Saint George's respiratory questionnaire
COPD patients without bronchiectasis; All patients will receive standard therapy for AECOPD. Additional for this study are: Sputum induction, Skin prick test, Questionnaires	Procedure: Sputum induction; Patients will have to puff 200µg of salbutamol (metered-dose inhaler with spacer device). After 10 minutes FEV1 will be measured with MIR spirobank. If FEV1 is >= 30% we can safely proceed with sputum induction. An ultrasonic nebulizer will be used to induce sputum. 4% sodiumchloride will be inhaled. Induction will be performed at 5-min intervals until a sample of good quality is obtained. Sodiumchloride of 5% will be used if no good sample is obtained after two intervals with the 4% solution. Maximal time of induction will be 20 minutes. Subjects will spit saliva into one container and rinse the mouth thoroughly with water before coughing sputum into another sterile container. Samples will be refrigerated at 4°C and processed within 24 hours of collection.; Procedure: Skin prick test; Skin Prick Test is a reliable method to diagnose IgE-mediated allergic disease. It is minimally invasive and results are immediately available. Interpretation utilizes the presence and degree of cutaneous reactivity as a surrogate marker for sensitization. A positive control, a negative control and Aspergillus fumigatus will be tested. Location will be Protocol version 1 3/11/2014 marked on the volar aspect of the forearm and drops of each solution will be placed (>= 2cm between drops). A single-head metal lancet will be pressed through the drop of allergen extract and held against the skin for at least 1 second. A new lancet will be utilized for each drop. A wheal diameter of >= 3mm is a positive result.; Other: Questionnaires; MRC: Medical Research Council Scale CAT: COPD Assessment Test SGRQ: Saint George's respiratory questionnaire

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bronchiectasis	immediate

Secondary Outcome Measures

Outcome Measure	Time Frame
Vitamin D	immediate
Prevalence of Aspergillus sensitization	max 12weeks
Prevalence of Aspergillus isolation in sputum	max 12weeks

Collaborators and Investigators

• Sponsor: Wim Janssens

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (ANTICIPATED): December 1, 2016
• Study Completion (ANTICIPATED): May 1, 2017

Study Registration Dates

• First Submitted: January 5, 2015
• First Submitted That Met QC Criteria: January 5, 2015
• First Posted (ESTIMATE): January 6, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): August 24, 2015
• Last Update Submitted That Met QC Criteria: August 21, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Vitamin D; COPD; Chronic Obstructive Pulmonary Disease; Bronchiectasis; Sensitization; Aspergillus fumigatus
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: S57222