Effect on Bronchodilation Response and Ventilation Heterogeneity of Different Inhalation Volumes in COPD (BREATH COPD)

Effect on Bronchodilatation Response and Ventilation Heterogeneity of Different Inhalation Volumes in COPD: the BREATH COPD Study

During bronchodilator tests, it's common to ask patients with asthma or chronic obstructive pulmonary disease (COPD) to take bronchodilator therapy by inhaling after a maximal exhalation, when the respiratory system volume equals the residual volume. The same maneuver is required for the chronic therapy.

Nevertheless, in patients with COPD the distribution of ventilation is more heterogeneous, especially when lung volumes are closer to residual volume . It is therefore predictable that the distribution of air volume containing bronchodilator that has been inhaled at residual volume is more heterogeneous than at higher volumes, such as at functional residual capacity. Accordingly, the bronchodilator can be preferentially distributed in more open airways than in less patent ones, with a heterogeneous distribution of the medication. Therefore, the overall bronchodilation should be greater when the drug inhalation is performed at functional residual capacity than at residual volume.

It is common knowledge that the effectiveness of bronchodilator therapy with pMDI in subjects with COPD is greatly affected by the inhalation technique, which can be difficult to perform for many patients. Therefore, in addition to the possibility that inhalation of bronchilation therapy at residual volume could lower the drug effectiveness, this maneuver complicates the sequence of actions required to the patient, enhancing the risk of errors and decreasing the aderence to treatment.

The aim of this study is to investigate whether the inhalation of a bronchodilator at different lung volumes can affect its effectiveness in terms of respiratory function, in patients with COPD.

Assuming that the bronchodilator effectiveness is equal or greater when inhaled at functional residual capacity rather than at residual volume, the inhalation maneuver can be simplified for patients with COPD.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Injury; COPD
• Intervention / Treatment: Other: Inhalation of bronchodilation therapy at FRC; Other: Inhalation of bronchodilation therapy at RV

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Pierachille Santus, PhD,MD,Prof; Phone Number: 0239042801; Email: pierachille.santus@unimi.it

Study Locations

• Italy
  • Milan, Italy, 20157
    • L. Sacco Hospital
    • Contact: Pierachille Santus, MD, PhD; Phone Number: 0239042801; Email: pierachille.santus@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with COPD diagnosis (VEMS/FVC after bronchodilatation <0.7) will be enrolled in a stable state of disease, diagnosed from at least 12 months [GOLD].

Description

Inclusion Criteria:

• age above 40 years old;
• history of smoking equal or above 10 PKYs;
• VEMS after bronchodilatation ≤ 70%,
• medical Necessity to perform a bronchodilatation test.

Exclusion Criteria:

• history of bronchial asthma or other chronic respiratory diseases such as pulmonary fibrosis;
• uncontrolled cardiovascular diseases at the time of the visit;
• current pregnancy;
• incapacity to execute lung function tests for cognitive impairment, substance abuse or claustrophobia;
• known hypersensitivity or intolerance to salbutamol.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with COPD; Patients with COPD diagnosis (VEMS/FVC after bronchodilatation <0.7) will be enrolled in a stable state of disease, diagnosed from at least 12 months [GOLD]. Each patient will be studied during three visits. In the first visit it will be established the patient eligibility. Furthermore, the patient will be able to familiarize with the experimental procedure. Chronic inhalation therapy will be suspended 24 (long action) and 8 (short action) hours before the second and third visit. If a patient is on tiotropium bromide, it will be required to be suspended 7 days before the visit. During the second and third visit, which will be scheduled 30 days one from another, the patient will be asked to inhale the bronchodilator (salbutamol pMDI, 400 µg) with a spacer from VR or FRC, in a random order. Before and after the administration it will be asked to the patient to execute a spirometry, a plethysmography, a lung diffusion test, and the NEP technique.

Other: Inhalation of bronchodilation therapy at FRC; the patient will be asked to inhale the bronchodilator (salbutamol pMDI, 400 µg) with a spacer from FRC (functional residual capacity, in a random order, with the assistance of an operator. The spacer will be connected to a Fleish flowmeter placed in series with the pMDI device. The valve included in the spacer will guarantee that only the air inhaled by the patient will pass through the flowmeter, reducing the risk of contamination. In both cases a low inspiratory flux and a period of apnea after inhalation of 10 seconds will be used. Before and after the administration it will be asked to the patient to execute a spirometry, a plethysmography, a lung diffusion test, and the NEP technique. These will allow the characterization of the bronchodilator effect in terms of static and dynamic volumes, heterogeneity of ventilation distribution and volume of closure, expiration flux-limitation.; Other: Inhalation of bronchodilation therapy at RV; the patient will be asked to inhale the bronchodilator (salbutamol pMDI, 400 µg) with a spacer from VR , with the assistance of an operator. The spacer will be connected to a Fleish flowmeter placed in series with the pMDI device. The valve included in the spacer will guarantee that only the air inhaled by the patient will pass through the flowmeter, reducing the risk of contamination. In both cases a low inspiratory flux and a period of apnea after inhalation of 10 seconds will be used. Before and after the administration it will be asked to the patient to execute a spirometry, a plethysmography, a lung diffusion test, and the NEP technique. These will allow the characterization of the bronchodilator effect in terms of static and dynamic volumes, heterogeneity of ventilation distribution and volume of closure, expiration flux-limitation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of bronchodilation therapy inhaled at Functional Residual Capacity (FRC) on Forced Expiratory Volume in 1 second (FEV1)	Assuming that the bronchodilator effectiveness is equal or greater when inhaled at functional residual capacity rather than at residual volume, the inhalation maneuver can be simplified for patients with COPD.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects on change in phase III slope of the closing volume curve	Efficacy of bronchodilation therapy inhaled at FRC on reducing phase III slope of the closing volume, as compared to bronchodilation therapy inhaled at RV	1 year
Effects on forced vital capacity (FVC)	Efficacy of bronchodilation therapy inhaled at FRC on static and dynamic lung volumes as compared to bronchodilation therapy inhaled at RV	1 year
Effects on vital capacity (VC)	Efficacy of bronchodilation therapy inhaled at FRC on static and dynamic lung volumes as compared to bronchodilation therapy inhaled at RV	1 year
Effects on residual volume (RV)	Efficacy of bronchodilation therapy inhaled at FRC on static and dynamic lung volumes as compared to bronchodilation therapy inhaled at RV	1 year
Effects on total lung capacity (TLC)	Efficacy of bronchodilation therapy inhaled at FRC on static and dynamic lung volumes as compared to bronchodilation therapy inhaled at RV	1 year
Effects on sensation of dyspnea as measured by modified Medical Research Council (mMRC) score	Efficacy of bronchodilation therapy at functional residual capacity on sensation of dyspnea	1 year
Effects on specific airway resistance (sRAW)	Efficacy of bronchodilation therapy at functional residual capacity on specific pulmonary resistances	1 year

Collaborators and Investigators

• Sponsor: University of Milan
• Collaborators: Department of Clinical and Surgical Pathophysiology and Transplantation, University of Milan

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 15, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Thoracic Injuries; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Lung Injury
• Other Study ID Numbers: BREATHCOPD2022

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