Effects of Acute Long-acting Bronchodilation on Oxygenation and Peripheral Ventilation in COPD

Study Overview
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Brief Summary
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The goal of this clinical trial was to compare the action of long-acting ß2-agonists (LABA-olodaterol) and muscarinic antagonists (LAMA-tiotropium) on tissue oxygenation in COPD considering their impact on proximal and peripheral ventilation and, eventually, on lung capillary volume. The hypothesis was that LABA would have a more peripheral effect than LAMA (due to the opposite gradient of their receptors) and better peripheral ventilation would result in a greater oxygenation. Before and after LABA (visit 1) and LAMA (visit 2) inhalation, COPD participants were asked to perform single-breath washout and forced oscillation tests, double diffusion technique and spirometry, while transcutaneous oxygenation was continuously recorded.

Detailed Description
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Slopes of He (SHe) and SF6 (SSF6) from single-breath washout test (SBWO) (assessing ventilation heterogeneities at the level of pre- and intra-acinar bronchioles, respectively) (quadruple model, LR6000 Logan-Sinclair, Rochester, UK), respiratory system resistance (R5, R5-R19) and reactance (X5, AX, Fres) from forced oscillation test (FOT) (Resmon Pro, ResTech, Italy), lung capillary volume (Vc) from double diffusion of NO and CO (DLNO/DLCO) (Hyp'Air compact, Medisoft, Dinant, Belgium), and FEV1 from spirometry (Zan®, Oberthulba, Germany) were evaluated before and after LABD administered via a spacer device: during the first visit, before, 30 minutes and 2 hours after inhalation of 4 puffs of 2,5 µg of olodaterol (LABA); during the second visit, before, 40 minutes and 2 hours after the administration of 4 puffs of 2,5 µg of tiotropium (LAMA). Transcutaneous oximetry (Perimed232©, Järfälla, Sweden) was monitored continuously during the 2 hours of each visit.

Official Title
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Comparison of Bronchodilation and Oxygenation Patterns Induced by Long-acting β2-agonists and Muscarinic Antagonists in Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: LABA
* Drug: LAMA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD diagnosis according to international criteria Exclusion Criteria: inability to perform the tests or to maintain the washout period an exacerbation within the previous 6 weeks a diagnosis of asthma or another chronic respiratory disease that could influence the results of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A prospective, clinical, uncontrolled, single-blind, cross-over trial that included 2 visits over 2-3 days. Assessments were performed before and after long-acting bronchodilation (LABD): during the first visit, before, 30 minutes and 2 hours after inhalation of olodaterol (LABA); during the second visit, before, 40 minutes and 2 hours after the administration of 4 puffs of 2,5 µg of tiotropium (LAMA).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LABA (olodaterol)<br>After 4-5 days washout period, during the first visit, participants received a long-acting beta2-agonist (LABA) | Drug: LABA<br>* Inhalation of 4 puffs of 2,5 µg of a long-acting beta2-agonist (LABA-olodaterol) administered via a spacer device<br>* Other names: Striverdi Respimat;|
| Experimental: LAMA (tiotropium)<br>Two days after the first visit, during the second visit , participants received a long-acting muscarinic antagonist (LAMA) | Drug: LAMA<br>* Inhalation of 4 puffs of 2,5 µg of a long-acting muscarinic antagonist (LAMA-tiotropium) administered via a spacer device<br>* Other names: Spiriva Respimat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue oxygenation (TcO2) change from baseline | Transcutaneous oxygen (TcO2) evaluated continuously with a transcutaneous oximeter | 120 minutes post-drug-administration | 
| Tissue oxygenation (TcO2) change from baseline | Transcutaneous oxygen (TcO2) evaluated continuously with a transcutaneous oximeter | 30 (LABA)/40 (LAMA) minutes post-drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope of Helium (SHe) change from baseline | SHe from single-breath washout test (SBWO) assessing peripheral ventilation heterogeneities | 120 minutes post-drug administration | 
| Slope of Helium (SHe) change from baseline | SHe from single-breath washout test (SBWO) assessing peripheral ventilation heterogeneities | 30 (LABA)/40 (LAMA) minutes post-drug administration | 
| Area under reactance curve from 5 Hz (AX) change from baseline | AX from forced oscillation test (FOT) evaluating the peripheral lung function | 120 minutes post-drug administration | 
| Area under reactance curve from 5 Hz (AX) change from baseline | AX from forced oscillation test (FOT) evaluating the peripheral lung function | 30 (LABA)/40 (LAMA) minutes post-drug administration | 
| Reactance at 5 Hz (X5) change from baseline | X5 from forced oscillation test (FOT) also evaluating the peripheral lung function | 30 (LABA)/40 (LAMA) minutes post-drug administration | 
| Resonant frequency (Fres) change from baseline | Fres from forced oscillation test (FOT) also evaluating the peripheral lung function | 120 minutes post-drug administration | 
| Resonant frequency (Fres) change from baseline | Fres from forced oscillation test (FOT) also evaluating the peripheral lung function | 30 (LABA)/40 (LAMA) minutes post-drug administration | 
| Peripheral resistance (R5-R19) change from baseline | Peripheral resistance, assessed as frequency dependence of resistance (R5-R19) from forced oscillation test (FOT) also evaluating the peripheral lung function | 120 minutes post-drug administration | 
| Peripheral resistance (R5-R19) change from baseline | Peripheral resistance, assessed as frequency dependence of resistance (R5-R19) from forced oscillation test (FOT) also evaluating the peripheral lung function | 30 (LABA)/40 (LAMA) minutes post-drug administration | 
| Lung capillary volume (Vc) change from baseline | Vc from single-breath double diffusion technique of nitric oxide (NO) and carbon monoxide (CO) (DLNO/DLCO) | 120 minutes post-drug administration | 
| Lung capillary volume (Vc) change from baseline | Vc from single-breath double diffusion technique of nitric oxide (NO) and carbon monoxide (CO) (DLNO/DLCO) | 30 (LABA)/40 (LAMA) minutes post-drug administration | 
| Forced Expiratory Volume in 1 Second (FEV1) change from baseline | FEV1 from spirometry | 120 minutes post-drug administration | 
| Forced Expiratory Volume in 1 Second (FEV1) change from baseline | FEV1 from spirometry | 30 (LABA)/40 (LAMA) minutes post-drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxygen, long-acting ß2-agonist, long-acting muscarinic antagonist, gas exchange, small airways, lung capillary volume