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Respiratory Impedance and Obliterative Bronchiolitis (FOT-BOS)

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ClinicalTrials.gov Identifier: NCT01255449
Recruitment Status : Completed
First Posted : December 7, 2010
Results First Posted : January 31, 2013
Last Update Posted : January 31, 2013
Sponsor:
Information provided by (Responsible Party):
Giovanni Barisione, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Tracking Information
First Submitted Date  ICMJE December 6, 2010
First Posted Date  ICMJE December 7, 2010
Results First Submitted Date  ICMJE September 18, 2012
Results First Posted Date  ICMJE January 31, 2013
Last Update Posted Date January 31, 2013
Study Start Date  ICMJE December 2010
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2012)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: December 6, 2010)
Changes in within-breath total respiratory input impedance following hematopoietic stem cell transplantation (HSCT) [ Time Frame: Before and at 2-wk intervals onward after HSCT ]
Changes in within-breath total respiratory input impedance (Zrs), resistance (Rrs) and reactance (Xrs) after HSCT. Zrs, Rrs and Xrs will be measured at baseline and 30 min after albuterol inhalation
Change History Complete list of historical versions of study NCT01255449 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2012)
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
Original Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2010)
Changes in standard pulmonary function tests following hematopoietic stem cell transplantation (HSCT) [ Time Frame: Before and at 2-wk intervals onward after HSCT ]
Changes in standard pulmonary function tests will be measured at baseline and 30 min after albuterol inhalation
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Respiratory Impedance and Obliterative Bronchiolitis
Official Title  ICMJE Predictive Value of Within-breath Respiratory Input Impedance in the Early Diagnosis of Obliterative Bronchiolitis After Allogeneic Hematopoietic Stem Cell Transplantation
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Hematopoietic Stem Cell Transplantation
  • Obliterative Bronchiolitis
Intervention  ICMJE Drug: albuterol
400 mcg by inhalation
Other Name: Broncovaleas pressurized solution
Study Arms  ICMJE 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.
Intervention: Drug: albuterol
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 22, 2012)
26
Original Estimated Enrollment  ICMJE
 (submitted: December 6, 2010)
200
Actual Study Completion Date  ICMJE June 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01255449
Other Study ID Numbers  ICMJE FOT-BOS-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Giovanni Barisione, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Study Sponsor  ICMJE IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Giovanni Barisione, MD IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
PRS Account IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Verification Date December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP