Evaluating Bronchodilator Response in Patients With Bronchiectasis

Although patients with bronchiectasis tend to have non reversible obstructive patterns on pulmonary function tests (PFTs), reversible obstruction is not uncommon. While bronchodilator response (BDR) is a main characteristic of asthma, the pathophysiology causing this phenomenon in bronchiectasis patients is less clear.

The goal of this clinical trial is to assess BDR in patients with bronchiectasis.

The main aims of this study:

1. To evaluate the role of bronchodilators in BDR testing of patients with bronchiectasis.
2. Characterize and compare BDR between different subgroups of patients with bronchiectasis, and compared to patients without bronchiectasis (healthy controls).
3. Identify demographics and other clinical variables associated with positive BDR

Participants will be taking a series of three spirometry tests: After the first spirometry testing, patients will be randomly assigned to receive bronchodilators as per bronchodilator response protocol (Salbutamol, 100 mcg, 4 puffs via spacer) or four puffs of placebo. After a waiting time of 15 minutes, spirometry will be repeated. Following the second spirometry testing those who received salbutamol will now receive placebo and those receiving placebo will receive Salbutamol. After a second period of 15 minutes, a third series of spirometry will be recorded.

Study Overview

• Status: Recruiting
• Conditions: Bronchiectasis; Cystic Fibrosis; Bronchiolitis Obliterans; Primary Ciliary Dyskinesia; Primary Immune Deficiency
• Intervention / Treatment: Diagnostic test: spirometry; Drug: Salbutamol; Drug: placebo

Detailed Description

Bronchiectasis are defined as irreversible dilatation of the bronchial tree. Patients with bronchiectasis suffer of chronic cough and sputum production, and are predisposed to recurrent airway infections. Many systemic diseases can cause bronchiectasis: cystic fibrosis (CF), primary ciliary dyskinesia (PCD), primary immune deficiencies (PID) and idiopathic bronchiectasis (IB) represent a significant proportion of patients with bronchiectasis starting in early age.

Pulmonary function testing (PFT) and specifically forced expiratory volume in one second (FEV1) is a common modality used to estimate lung disease progression and pulmonary exacerbations in patients with bronchiectasis. Although patients with bronchiectasis tend to have non reversible obstructive patterns on pulmonary function tests (PFTs), reversible obstruction is not uncommon. While bronchodilator response (BDR) is a main characteristic of asthma, the pathophysiology causing this phenomenon in bronchiectasis patients is less clear. The improvement in FEV1 after inhalation of bronchodilators can be attributed to bronchodilation or improved mucociliary clearance. It can be speculated that for some of the bronchiectasis patients, hyper-reactive airways or asthma can contribute to the reversible pattern. Despite the wide scale use of bronchodilators in bronchiectasis the evidence for its efficacy is lacking. While some studies found that BDR is associated with more severe disease, other studies did not find such associations.

According to ATS/ERS statement, the proper way to determine BDR, is by first recording three attempts of spirometry, then delivering bronchodilators, and after a waiting time, obtaining again at least three attempts of spirometry. The most resent ATS/ERS technical standard suggests that change of >10% relative to the predicted value for FEV1 or forced vital capacity (FVC) be considered a positive BDR.

While in most scenarios it is reasonable to assume that the change in FEV1 measured after the waiting time can be attributed solely to the affect of bronchodilators, this is not necessarily the case in bronchiectatic diseases. Theoretically, in bronchiectasis, the forced expiration maneuver used in spirometry testing can potentially cause changes in lung function, for example by inducing cough and mobilization of sputum. Evidence for this assumption can be seen in that respiratory therapy in terms if positive expiratory pressure (PEP) therapy can improve various parameters of lung function when tested again closely after the therapy.

The goal of this study is to determine if bronchodilator response in bronchiectatic disease might be influenced by other factors apart from the direct effect of bronchodilators. Secondary objectives are to assess if BDR is associated with age, gender, specific bronchiectatic disease, baseline FEV1, and other clinical factors such as sputum cultures, IgE levels, eosinophil levels, computed tomography (CT) score, family history of asthma and use of inhaled steroids.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mordechai Pollak, MD, MSc; Phone Number: +972542388651; Email: m_pollak@rambam.health.gov.il

Study Locations

• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Campus
    • Contact: Mordechai Pollak, MD, MSc; Phone Number: 0542388651; Email: morduchp@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with bronchiectasis confirmed by CT scan
• No recent pulmonary exacerbation as determined by prescription of systemic antibiotics in 7 days prior to BDR testing
• No use of long-acting beta agonists (LABA) 12 hours before BDR testing or short acting beta agonist (SABA) 4 hours before testing

Exclusion Criteria:

• Patients under 5 years of age
• Patients incapable to perform proper spirometry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Salbutamol first; Individuals included in this arm will receive 4 puffs of Salbutamol prior to the second set of spirometry testing, and 4 puffs of Placebo prior to the third set of spirometry.	Diagnostic test: spirometry; participants will undertake spirometry testing before and after bronchodilators and placebo; Other Names: pulmonary function testing; Drug: Salbutamol; Salbutamol inhalation to determine bronchodilator response; Other Names: bronchodilator; Drug: placebo; placebo inhalation prior to repeating spirometry
Other: Placebo First; Individuals included in this arm will receive 4 puffs of placebo prior to the second set of spirometry testing and 4 puffs of Salbutamol prior to the third set of spirometry testing.	Diagnostic test: spirometry; participants will undertake spirometry testing before and after bronchodilators and placebo; Other Names: pulmonary function testing; Drug: Salbutamol; Salbutamol inhalation to determine bronchodilator response; Other Names: bronchodilator; Drug: placebo; placebo inhalation prior to repeating spirometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchodilator response compared to placebo (change in FEV1)	Bronchodilator response = change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation, compared to the same change after placebo. Results will be presented in "percent predicted" using global lung initiative (GLI) equations.	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
Bronchodilator response compared to placebo (change in FVC)	Bronchodilator response = change in forced vital capacity (FVC) from pre to post salbutamol inhalation, compared to the same change after placebo. Results will be presented in "percent predicted" using global lung initiative (GLI) equations.	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
response in specific bronchiectatic disease	assessment of bronchodilator response (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation) differences between different types of bronchiectatic disease (cystic fibrosis (CF), Primary ciliary dyskinesia (PCD), non CF - non PCD bronchiectatic disease) Results will be presented in "percent predicted" using global lung initiative (GLI) equations.	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
bronchiectasis compared to healthy controls	assessment of BDR (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation) differences between patients with bronchiectatic disease and healthy controls Results will be presented in "percent predicted" using global lung initiative (GLI) equations.	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
Bronchodilator response by age	Identify if bronchodilator response (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation, presented in "percent predicted" using global lung initiative (GLI) equations) is influenced by the age of the participant	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
Bronchodilator response by sex	Identify if bronchodilator response (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation, presented in "percent predicted" using global lung initiative (GLI) equations) is influenced by the biological sex of the participant	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
Bronchodilator response by bronchiectatic disease	Identify if bronchodilator response (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation, presented in "percent predicted" using global lung initiative (GLI) equations) is influenced by the specific bronchiectatic disease (cystic fibrosis (CF), Primary ciliary dyskinesia (PCD), non CF - non PCD bronchiectatic disease).	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
Bronchodilator response by use of inhaled steroids	Identify if bronchodilator response (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation, presented in "percent predicted" using global lung initiative (GLI) equations) is influenced by the use of inhaled corticosteroids.	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
Bronchodilator response by history of allergy	Identify if bronchodilator response (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation, presented in "percent predicted" using global lung initiative (GLI) equations) is influenced by personal history of allergy	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
Bronchodilator response by baseline FEV1	Identify if bronchodilator response (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation, presented in "percent predicted" using global lung initiative (GLI) equations) is influenced by baseline FEV1 as determined by the best FEV1 measured in the 6 months prior to the day of the study	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
Bronchodilator response by history of pseudomonas	Identify if bronchodilator response (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation, presented in "percent predicted" using global lung initiative (GLI) equations) is influenced by personal history of pseudomonas growing in sputum cultures	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)
Bronchodilator response by bronchiectasis severity	Identify if bronchodilator response (change in forced expiratory volume 1 second (FEV1) from pre to post salbutamol inhalation, presented in "percent predicted" using global lung initiative (GLI) equations) is influenced by the severity of bronchiectasis as measured by CT imaging using the Bhalla score	spirometry results will be collected in one clinic visit in three steps: *baseline *15 minutes after first intervention (placebo or salbutamol) *15 minutes after second intervention (placebo or salbutamol)

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus
• Investigators: Principal Investigator: Mordechai Pollak, MD, MSc, pediatric pulmonology institute, Ruth Rappaport children's hospital, Rambam medical center

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: May 31, 2023
• First Submitted That Met QC Criteria: June 30, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Bronchodilator response
• Additional Relevant MeSH Terms: Digestive System Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Neurologic Manifestations; Congenital Abnormalities; Infant, Newborn, Diseases; Bronchial Diseases; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Movement Disorders; Lung Diseases, Obstructive; Pancreatic Diseases; Abnormalities, Multiple; Bronchitis; Ciliopathies; Organizing Pneumonia; Graft vs Host Disease; Bronchiectasis; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Cystic Fibrosis; Dyskinesias; Bronchiolitis; Bronchiolitis Obliterans; Ciliary Motility Disorders; Bronchiolitis Obliterans Syndrome; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Bronchodilator Agents
• Other Study ID Numbers: 0025-23-RMB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No