Respiratory Impedance and Obliterative Bronchiolitis (FOT-BOS)

December 22, 2012 updated by: Giovanni Barisione, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Predictive Value of Within-breath Respiratory Input Impedance in the Early Diagnosis of Obliterative Bronchiolitis After Allogeneic Hematopoietic Stem Cell Transplantation

The aim of the present study will be to test the hypothesis that changes in within-breath total respiratory input impedance (Zrs) may provide an early evidence of obliterative bronchiolitis after allogeneic hematopoietic stem cell transplantation (HSCT). Before and after HSCT, Zrs will be measured by a modified forced oscillation technique (FOT) during spontaneous breathing both at baseline and 30 min after albuterol inhalation . Such technique may be particularly sensitive to small changes in lung mechanics observed in the early stages of peripheral airflow obstruction.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Detailed Description

1.0 INTRODUCTION

  • Shortly after the introduction of allogeneic HSCT in clinical practice, it was recognized that standard pulmonary function tests (PFTs) are sensitive enough to detect HSCT-related respiratory complications [PMID: 2661259; PIMD: 8823260]. Accordingly, the finding of a progressive obstructive abnormality of new onset was considered as the functional hallmark of obliterative bronchiolitis (OB) [PMID: 16338616; PMID: 19896545]. As a result, routinely performed spirometry has been proposed as a non-invasive tool to monitor the risk of OB in HSCT population [PMID: 17470622]. Yet, due to a peripheral airway involvement in OB, the sensitivity of conventional PFTs for early detection of OB is low [PMID: 2298060]. For instance, it does not exceed 75% in lung-transplanted population as the decrease of forced expiratory volume in 1 s (FEV1) may occur at a stage when the process is already irreversible and potentially life-threatening [PMID: 9246138].

2.0 EXPERIMENTAL HYPOTHESIS

  • Because the branching pattern of the bronchial tree results in an increasingly large number of small airways with a luminal diameter of less than 2 mm in peripheral generations, these airways contribute little to total pulmonary resistance [PMID: 5442364; PMID: 651978]. Intuitively, a large proportion of small airways may be damaged or obliterated without impairing any of the conventional PFTs. In this regard, a previous study [PMID: 12186817] pointed out that indexes of ventilation distribution may provide an early evidence of OB after lung transplantation. In particular, some authors [PMID: 12186817] have found that tests of ventilation distribution invariably deteriorated about 1 yr before a 20% decrease in FEV1 was apparent. Previous studies [PMID: 970731; PMID: 507525] showed that total respiratory input impedance (Zrs), measured by a forced oscillation technique (FOT) during spontaneous breathing, may be particularly sensitive to small changes in lung mechanics observed in the early stages of smoking-related airflow obstruction. Subsequently, it was developed a modified FOT to identify within-breath differences in Zrs, with values of Zrs representing the sum of respiratory system resistance (Rrs) and reactance (Xrs), the latter being the imaginary part of the former [PMID: 14979497; PMID: 19164347]. This method allows the assessment of more breaths and adds a potential quantitative evaluation of instantaneous inspiratory and expiratory Rrs and Xrs before and after external interventions such as a deep inspiration, bronchodilator drugs, etc. Although these effects can be identified when within-breath analysis is performed [PMID: 14979497], most published reports of oscillatory mechanics on chronic obstructive pulmonary disease (COPD) only report total respiratory cycle data [PMID: 1519830; PMID: 10489847].

3.0 STUDY RATIONALE

  • The aim of the present study will be to test the hypotheses that:

    1. post-HSCT changes in within-breath Rrs and Xrs may provide an earlier evidence of OB than standard PFTs. Indeed, the obliteration of terminal bronchioles, observed in up to 48% of OB patients following HSCT [PMID: 17470622], could make the real part of Zrs abnormally high [PMID: 5653219] and ventilation more heterogeneous;
    2. post-HSCT changes of airway responsiveness to acute bronchoactive interventions such as a deep inspiration to total lung capacity and/or a bronchodilator drug (i.e., albuterol) may be detected by our modified FOT. We speculate that these changes may represent an early sign of OB. Although a previous study from our group failed to find an increase in airway responsiveness after HSCT without pulmonary complications [PMID: 18684842], we have recently shown that airway smooth muscle tone may play an active role in the airflow obstruction of OB [PMID: 20724742].

4.0 STUDY DESIGN

  • Before and at regular intervals (2-4 wk onward) after HSCT, patients will attend our laboratory and perform all PFTs measurements in the same order. Firstly, the patient will breathe spontaneously through the modified FOT system for 5 min and then, without disconnecting from the apparatus, perform an inspiratory capacity maneuver and soon after resume spontaneous breathing for the next 2 min. Subsequently, spirometry, transmural total body plethysmography and CO diffusing capacity of the lung (standard PFTs) will be taken in triplicate. Thirty minutes after inhaling four separate doses of 100 μg of albuterol, the modified FOT measurements and standard PFTs will be repeated anew.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Genova, Italy, 16132
        • U.O. Medicina Preventiva e del Lavoro, Laboratorio di Fisiopatologia Respiratoria, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro

Participation Criteria

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Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • consecutive, clinically-stable, outpatients undergoing allogeneic HSCT (sourcing from bone marrow) for hematological malignancies
  • values of standard PFTs within normal range before HSCT
  • good collaboration during the maneuvers

Exclusion Criteria:

  • patients showing any spirometric and/or volumetric abnormality before HSCT
  • poor collaboration and/or coordination during the maneuvers
  • any clinically-significant respiratory disease (bronchial asthma, COPD, cystic fibrosis, etc.) before HSCT

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: albuterol
Twenty-six consecutive patients undergoing allogeneic HSCT for hematological malignancies were studied. All patients were in stable clinical conditions at the time of study. All patients received a myeloablative conditioning regimen either including or not including total body irradiation. Spirometry, lung volumes, FOT and lung CT scan were obtained before the start of conditioning treatment and, approximately, two months after HSCT. On each study day, all the above measurements were taken before and 30 min after inhaling four consecutive albuterol doses, of 100 mcg each, through a valved-holding chamber. DLco was measured only after bronchodilator inhalation.
Drug: albuterol
400 mcg by inhalation
Other Names:
  • Broncovaleas pressurized solution

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Airway Distensibility With Lung Inflation After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Time Frame: 2 weeks before and 2 months after HSCT
We studied 26 subjects, 2 weeks before and 2 months after HSCT. Within-breath respiratory system conductance (Grs) at 5, 11 and 19 Hz was measured by forced oscillation technique (FOT) at functional residual capacity (FRC) and total lung capacity (TLC)
2 weeks before and 2 months after HSCT

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Post-HSCT Changes in Lung Tissue Density
Time Frame: Before and 2 months after HSCT
Changes in lung tissue density were measured by quantitative computed tomography(CT) scan 2 weeks before and 2 months after HSCT
Before and 2 months after HSCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Giovanni Barisione, MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Publications and helpful links

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General Publications

Study record dates

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Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 6, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 7, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 31, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 22, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FOT-BOS-01

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