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

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

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.

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.

long-acting ß2-agonist, long-acting muscarinic antagonist, gas exchange, oxygen, small airways, lung capillary volume

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).

After 4-5 days washout period, during the first visit, participants received a long-acting beta2-agonist (LABA)

Two days after the first visit, during the second visit , participants received a long-acting muscarinic antagonist (LAMA)

Inhalation of 4 puffs of 2,5 µg of a long-acting beta2-agonist (LABA-olodaterol) administered via a spacer device

Inhalation of 4 puffs of 2,5 µg of a long-acting muscarinic antagonist (LAMA-tiotropium) administered via a spacer device

Peripheral resistance, assessed as frequency dependence of resistance (R5-R19) from forced oscillation test (FOT) also evaluating the peripheral lung function

Peripheral resistance, assessed as frequency dependence of resistance (R5-R19) from forced oscillation test (FOT) also evaluating the peripheral lung function

Vc from single-breath double diffusion technique of nitric oxide (NO) and carbon monoxide (CO) (DLNO/DLCO)

Vc from single-breath double diffusion technique of nitric oxide (NO) and carbon monoxide (CO) (DLNO/DLCO)

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

When published, the datasets used and/or analysed during the study will be available from the corresponding author on reasonable request.

The datasets used and/or analysed during the study will be available from the corresponding author on reasonable request.