Bronchodilator Responsiveness in Obliterative Bronchiolitis

NCT ID: NCT01112241

Last Updated: 2011-03-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2010-05-31

Brief Summary

This study has been designed to provide a substantial evidence of acute bronchodilator responsiveness to two sequentially inhaled drugs, a beta2-agonist (i.e., albuterol) and an anticholinergic (i.e., tiotropium bromide), in a group of patients who developed obliterative bronchiolitis after hematopoietic stem cell transplantation.

Detailed Description

Obliterative bronchiolitis is a life-threatening non-infectious pulmonary complication of allogeneic hematopoietic stem cell transplantation (HSCT). It is characterized by the development of an obstructive abnormality which has been considered to be insensitive to bronchodilator treatments. However, this knowledge stems from measurements of forced expiratory volume in 1 s (FEV1) which is relatively insensitive to changes in small airway caliber. Moreover, it is known from studies in chronic obstructive pulmonary disease that symptoms improve after bronchodilator treatment even when FEV1 is minimally increased and correlate with the reduction of lung hyperinflation, which is the major consequence of severe expiratory airflow limitation. Therefore, measurements of airway caliber by parameters not affected by volume history and absolute lung volumes are preferable for assessing the effect of bronchodilator interventions.

In the current study, the bronchodilators responsiveness will be assessed by using not only spirometry but also measurements of absolute lung volumes and the forced expiratory flow of a partial maneuver (V'part) started from submaximal lung inflation, thus free of volume history effects.

Conditions

Obliterative Bronchiolitis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

albuterol-tiotropium

At visit 1, lung function measurements will be performed in triplicate before and 90 min after inhaling four separate doses of 100 μg of albuterol (Ventolin®) and soon after 18 μg of tiotropium bromide \[Spiriva®\] to ensure maximal or near-maximal bronchodilation. Albuterol will be given by a metered-dose inhaler connected to a valved-holding chamber (Volumatic®) and tiotropium by a dry-powder device (Handihaler®).

Group Type: EXPERIMENTAL

albuterol plus tiotropium

Intervention Type: DRUG

Four separate doses of 100 μg of albuterol and 18 μg of tiotropium bromide. Albuterol will be given by a metered-dose inhaler connected to a valved-holding chamber and tiotropium by a dry-powder device.

Interventions

albuterol plus tiotropium

Four separate doses of 100 μg of albuterol and 18 μg of tiotropium bromide. Albuterol will be given by a metered-dose inhaler connected to a valved-holding chamber and tiotropium by a dry-powder device.

Intervention Type: DRUG

Other Intervention Names

Ventolin® and Spiriva®

Eligibility Criteria

Inclusion Criteria

• Obliterative bronchiolitis (OB) following allogeneic HSCT
• FEV1 to slow inspiratory vital capacity (VC) ratio (FEV1/VC)<5th percentile
• FEV1 <75% predicted or absolute FEV1 fall >10% of pre-HSCT value
• evidence of OB by computed tomography scanning
• negative microbiological yields in bronchoalveolar lavage fluid
• chronic graft-versus-host disease score >0
• negative history for bronchial asthma, chronic obstructive pulmonary disease or other significant respiratory disease.

Exclusion Criteria

• inability to perform lung function maneuvers
• pre-existent chronic lung disease other than OB

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

OTHER

Sponsor Role: lead

Responsible Party

Unit of Preventive and Occupational Medicine - Laboratory of Respiratory Pathophysiology

Principal Investigators

Giovanni Barisione, MD

Role: PRINCIPAL_INVESTIGATOR

Unit of Preventive and Occupational Medicine, University Hospital San Martino, Genoa, Italy

Locations

Unit of Preventive and Occupational Medicine - Laboratory of Respiratory Pathophysiology, University Hospital San Martino

Genoa, , Italy

Countries

Italy

References

Pellegrino R, Rodarte JR, Brusasco V. Assessing the reversibility of airway obstruction. Chest. 1998 Dec;114(6):1607-12. doi: 10.1378/chest.114.6.1607.

Reference Type: BACKGROUND

PMID: 9872196 (View on PubMed)

Barisione G, Bacigalupo A, Crimi E, Van Lint MT, Lamparelli T, Brusasco V. Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation. Eur Respir J. 2008 Dec;32(6):1576-82. doi: 10.1183/09031936.0139807. Epub 2008 Aug 6.

Reference Type: BACKGROUND

PMID: 18684842 (View on PubMed)

Barisione G, Bacigalupo A, Crimi E, Brusasco V. Acute bronchodilator responsiveness in bronchiolitis obliterans syndrome following hematopoietic stem cell transplantation. Chest. 2011 Mar;139(3):633-639. doi: 10.1378/chest.10-1442. Epub 2010 Aug 19.

Reference Type: RESULT

PMID: 20724742 (View on PubMed)

Other Identifiers

BOS-01

Identifier Type: -

Identifier Source: org_study_id