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

NCT05381415 | Not Yet Recruiting

• 1 other identifier: BREATHCOPD2022
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

COPD; Lung Injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Effects on change in phase III slope of the closing volume curve

  1 year

• Effects on forced vital capacity (FVC)

  1 year

• Effects on vital capacity (VC)

  1 year

• Effects on residual volume (RV)

  1 year

• Effects on total lung capacity (TLC)

  1 year

Study Arms (1)

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; Other: Inhalation of bronchodilation therapy at RV

Interventions

Inhalation of bronchodilation therapy at FRC OTHER

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.

Patients with COPD

Inhalation of bronchodilation therapy at RV OTHER

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.

Patients with COPD

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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 \[GOLD\].

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Department of Clinical and Surgical Pathophysiology and Transplantation, University of Milan: collaborator
• University of Milan: lead

Study Sites (1)

L. Sacco Hospital

Milan, 20157, Italy

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Lung Injury

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thoracic Injuries; Wounds and Injuries

Central Study Contacts

Pierachille Santus, PhD,MD,Prof

CONTACT

0239042801; pierachille.santus@unimi.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pulmonary Medicine

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 19, 2022
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)