BD-OB: Bronchodilator Responsiveness in Obliterative Bronchiolitis

• Sponsor: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy (Other)
• Overall Status: Completed
• CT.gov ID: NCT01112241
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arm: 1
• Duration (Days): 30
• Patients Per Site Per Month: 17.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obliterative Bronchiolitis	Drug: albuterol plus tiotropium	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Acute Bronchodilator Responsiveness in Obliterative Bronchiolitis (OB) Following Hematopoietic Stem Cell Transplantation
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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®).

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.; Other Names: Ventolin® and Spiriva®

Outcome Measures

Primary Outcome Measures

1. Per Cent Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators [Baseline and 90 min 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].

2. Absolute Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators [Baseline and 90 min 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].

3. Per Cent Change of Forced Vital Capacity (FVC) After Bronchodilators [Baseline and 90 min 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].

4. Absolute Change of Forced Vital Capacity (FVC) After Bronchodilators [Baseline and 90 min 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].

5. Per Cent Change of Instantaneous Maximal Forced Expiratory Flow (V'Max) After Bronchodilators [Baseline and 90 min 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].

6. Per Cent Change of Partial Forced Expiratory Flow (V'Part) After Bronchodilators [Baseline and 90 min 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].

7. Per Cent Change of Residual Volume (RV) After Bronchodilators [Baseline and 90 min 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].

8. Absolute Change of Residual Volume (RV) After Bronchodilators [Baseline and 90 min 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].

9. Per Cent Change of Functional Residual Capacity (FRC) After Bronchodilators [Baseline and 90 min 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].

10. Absolute Change of Functional Residual Capacity (FRC) After Bronchodilators [Baseline and 90 min 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].

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Unit of Preventive and Occupational Medicine - Laboratory of Respiratory Pathophysiology, University Hospital San Martino	Genoa		Italy	16132

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Giovanni Barisione, MD, Unit of Preventive and Occupational Medicine, University Hospital San Martino, Genoa, Italy

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• ClinicalTrials.gov Identifier: NCT01112241
• Other Study ID Numbers: BOS-01
• First Posted: Apr 28, 2010
• Last Update Posted: Mar 2, 2011
• Last Verified: Apr 1, 2010

• Keywords provided by , ,: Obliterative bronchiolitis; Bronchodilator responsiveness; Partial forced expiratory flow; Lung volumes
• Additional relevant MeSH terms: Bronchiolitis; Bronchiolitis Obliterans; Albuterol; Tiotropium Bromide

Study Results

Participant Flow

Recruitment Details	Between April 2010 and May 2010, seventeen consecutive bronchiolitis obliterans (BOS) patients following hematopoietic stem cell transplantation (HSCT) were studied.
Pre-assignment Detail	In all patients, airflow obstruction was found at spirometry between 14 and 72 months (median, 41 months) after HSCT. The diagnosis of BOS was confirmed by fulfilment of currently updated criteria [Filipovich AH et al. Biol Blood Marrow Transplant 2005; 11:945-956][Chien JW et al. Biol Blood Marrow Transplant 2010; 16:S106-S114].

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Period Title: Overall Study
STARTED	17
COMPLETED	17
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Overall Participants	17
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48 (12)
Sex: Female, Male (Count of Participants)
Female	5 29.4%
Male	12 70.6%
Region of Enrollment (participants) [Number]
Italy	17 100%

Outcome Measures

1. Primary Outcome

Title	Per Cent Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following hematopoietic stem cell transplantation (HSCT) for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=4)	14 (1)
Unresponsives to bronchodilators (n=13)	7 (5)

2. Primary Outcome

Title	Absolute Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following hematopoietic stem cell transplantation (HSCT) for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=4)	0.26 (0.06)
Unresponsives to bronchodilators (n=13)	0.12 (0.09)

3. Primary Outcome

Title	Per Cent Change of Forced Vital Capacity (FVC) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following hematopoietic stem cell transplantation (HSCT) for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=5)	24 (13)
Unresponsives to bronchodilators (n=12)	2 (4)

4. Primary Outcome

Title	Absolute Change of Forced Vital Capacity (FVC) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following hematopoietic stem cell transplantation (HSCT) for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=5)	0.65 (0.37)
Unresponsives to bronchodilators (n=12)	0.07 (0.15)

5. Primary Outcome

Title	Per Cent Change of Instantaneous Maximal Forced Expiratory Flow (V'Max) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following HSCT for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=4)	66 (17)
Unresponsives to bronchodilators (n=13)	14 (14)

6. Primary Outcome

Title	Per Cent Change of Partial Forced Expiratory Flow (V'Part) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following hematopoietic stem cell transplantation (HSCT) for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=9)	59 (26)
Unresponsives to bronchodilators (n=8)	17 (7)

7. Primary Outcome

Title	Per Cent Change of Residual Volume (RV) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following hematopoietic stem cell transplantation (HSCT) for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=8)	19 (5)
Unresponsives to bronchodilators (n=9)	0 (5)

8. Primary Outcome

Title	Absolute Change of Residual Volume (RV) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following hematopoietic stem cell transplantation (HSCT) for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=8)	0.65 (0.37)
Unresponsives to bronchodilators (n=9)	0.00 (0.10)

9. Primary Outcome

Title	Per Cent Change of Functional Residual Capacity (FRC) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following hematopoietic stem cell transplantation (HSCT) for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=4)	16 (6)
Unresponsives to bronchodilators (n=13)	2 (5)

10. Primary Outcome

Title	Absolute Change of Functional Residual Capacity (FRC) After Bronchodilators
Description	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].
Time Frame	Baseline and 90 min after bronchodilators

Outcome Measure Data

Analysis Population Description

Seventeen consecutive, clinically-stable, Caucasian outpatients, presenting with mild-to-very-severe obliterative bronchiolitis following hematopoietic stem cell transplantation (HSCT) for hematological malignancies, were studied. They were diagnosed from 460 patients (253 males, 207 females) undergoing HSCT (sourcing from bone marrow).

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
Measure Participants	17
Responsives to bronchodilators (n=4)	0.78 (0.34)
Unresponsives to bronchodilators (n=13)	0.07 (0.16)

Adverse Events

Arm/Group Title	Albuterol Plus Tiotropium
Arm/Group Description	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®).
All Cause Mortality
	Albuterol Plus Tiotropium
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Albuterol Plus Tiotropium
	Affected / at Risk (%)	# Events
Total	0/17 (0%)
Other (Not Including Serious) Adverse Events
	Albuterol Plus Tiotropium
	Affected / at Risk (%)	# Events
Total	0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.