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NCT Number: NCT05381415

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

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.

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Key information

Age range

40 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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.

Primary outcomes

  1. Efficacy of bronchodilation therapy inhaled at Functional Residual Capacity (FRC) on Forced Expiratory Volume in 1 second (FEV1)

    Time frame: 1 year

    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.

Secondary outcomes

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

    Time frame: 1 year

    Efficacy of bronchodilation therapy inhaled at FRC on reducing phase III slope of the closing volume, as compared to bronchodilation therapy inhaled at RV

  2. Effects on forced vital capacity (FVC)

    Time frame: 1 year

    Efficacy of bronchodilation therapy inhaled at FRC on static and dynamic lung volumes as compared to bronchodilation therapy inhaled at RV

  3. Effects on vital capacity (VC)

    Time frame: 1 year

    Efficacy of bronchodilation therapy inhaled at FRC on static and dynamic lung volumes as compared to bronchodilation therapy inhaled at RV

  4. Effects on residual volume (RV)

    Time frame: 1 year

    Efficacy of bronchodilation therapy inhaled at FRC on static and dynamic lung volumes as compared to bronchodilation therapy inhaled at RV

  5. Effects on total lung capacity (TLC)

    Time frame: 1 year

    Efficacy of bronchodilation therapy inhaled at FRC on static and dynamic lung volumes as compared to bronchodilation therapy inhaled at RV

  6. Effects on sensation of dyspnea as measured by modified Medical Research Council (mMRC) score

    Time frame: 1 year

    Efficacy of bronchodilation therapy at functional residual capacity on sensation of dyspnea

  7. Effects on specific airway resistance (sRAW)

    Time frame: 1 year

    Efficacy of bronchodilation therapy at functional residual capacity on specific pulmonary resistances

Study contacts

Contact information is provided by the study sponsor or research team.

Pierachille Santus, PhD,MD,Prof

CONTACT

[email protected]

0239042801

Sponsors and collaborators

Lead sponsor

University of Milan

Other

Collaborators

  • Department of Clinical and Surgical Pathophysiology and Transplantation, University of Milan

Registry information

Official study title

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

Acronym: BREATH COPD

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
May 19, 2022
Registry last updated
May 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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