Bronchodilator Responsiveness in Obliterative Bronchiolitis

Obliterative Bronchiolitis Clinical Trial

— BD-OB  

Official title:

Acute Bronchodilator Responsiveness in Obliterative Bronchiolitis (OB) Following Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01112241
• Other study ID #: BOS-01
• Status: Completed
• Phase: Phase 4
• First received: April 27, 2010
• Last updated: February 28, 2011
• Start date: April 2010
• Est. completion date: May 2010

Study information

• Verified date: April 2010
• Source: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans
• Obliterative Bronchiolitis

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Italy	Unit of Preventive and Occupational Medicine - Laboratory of Respiratory Pathophysiology, University Hospital San Martino	Genoa

Sponsors (1)

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

Country where clinical trial is conducted

Italy, 

References & Publications (3)

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):633-9. doi: 10.1378/chest.10-1442. Epub 2010 Aug 19. — View Citation

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. — View Citation

Pellegrino R, Rodarte JR, Brusasco V. Assessing the reversibility of airway obstruction. Chest. 1998 Dec;114(6):1607-12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Per Cent Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators	Following albuterol plus tiotropium inhalation, FEV1 increments =12 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FEV1, expressed in liters (L), after bronchodilators - FEV1 (L) before bronchodilators/FEV1 (L) before bronchodilators x 100].	Baseline and 90 min after bronchodilators	No
Primary	Absolute Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators	Following albuterol plus tiotropium inhalation, FEV1 increments =0.20 liters (L) as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FEV1 (L) after bronchodilators - FEV1 (L) before bronchodilators].	Baseline and 90 min after bronchodilators	No
Primary	Per Cent Change of Forced Vital Capacity (FVC) After Bronchodilators	Following albuterol plus tiotropium inhalation, FVC increments =12 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FVC, expressed in liters (L), after bronchodilators - FVC (L) before bronchodilators/FVC (L) before bronchodilators x 100].	Baseline and 90 min after bronchodilators	No
Primary	Absolute Change of Forced Vital Capacity (FVC) After Bronchodilators	Following albuterol plus tiotropium inhalation, FVC increments =0.20 liters (L) compared with baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FVC (L) after bronchodilators - FVC (L) before bronchodilators].	Baseline and 90 min after bronchodilators	No
Primary	Per Cent Change of Instantaneous Maximal Forced Expiratory Flow (V'Max) After Bronchodilators	Following albuterol plus tiotropium inhalation, V'max increments =40 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to Pellegrino et al. [Chest 1998; 114:1607-1612]. They were calculated as follows: [V'max, expressed in liters.second-1 (L.s-1), after bronchodilators - V'max (L.s-1) before bronchodilators/V'max (L.s-1) before bronchodilators x 100].	Baseline and 90 min after bronchodilators	No
Primary	Per Cent Change of Partial Forced Expiratory Flow (V'Part) After Bronchodilators	Following albuterol plus tiotropium inhalation, V'part increments =40 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to Pellegrino et al. [Chest 1998; 114:1607-1612]. They were calculated as follows: [V'part, expressed in liters.second-1 (L.s-1), after bronchodilators - V'part (L.s-1) before bronchodilators/V'part (L.s-1) before bronchodilators x 100].	Baseline and 90 min after bronchodilators	No
Primary	Per Cent Change of Residual Volume (RV) After Bronchodilators	Following albuterol plus tiotropium inhalation, RV decrements =10 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [RV, expressed in liters (L), before bronchodilators - RV (L) after bronchodilators/RV (L) after bronchodilators x 100].	Baseline and 90 min after bronchodilators	No
Primary	Absolute Change of Residual Volume (RV) After Bronchodilators	Following albuterol plus tiotropium inhalation, RV decrements =0.30 liters (L) as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [RV (L), before bronchodilators - RV (L) after bronchodilators].	Baseline and 90 min after bronchodilators	No
Primary	Per Cent Change of Functional Residual Capacity (FRC) After Bronchodilators	Following albuterol plus tiotropium inhalation, FRC decrements =10 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [FRC, expressed in liters (L), before bronchodilators - FRC (L) after bronchodilators/FRC (L) after bronchodilators x 100].	Baseline and 90 min after bronchodilators	No
Primary	Absolute Change of Functional Residual Capacity (FRC) After Bronchodilators	Following albuterol plus tiotropium inhalation, FRC decrements =0.30 liters (L) as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [FRC (L), before bronchodilators - FRC (L) after bronchodilators].	Baseline and 90 min after bronchodilators	No