Trial Outcomes & Findings for Bronchodilator Responsiveness in Obliterative Bronchiolitis (NCT NCT01112241)
NCT ID: NCT01112241
Last Updated: 2011-03-02
Results Overview
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: \[FEV1, expressed in liters (L), after bronchodilators - FEV1 (L) before bronchodilators/FEV1 (L) before bronchodilators x 100\].
COMPLETED
PHASE4
17 participants
Baseline and 90 min after bronchodilators
2011-03-02
Participant Flow
Between April 2010 and May 2010, seventeen consecutive bronchiolitis obliterans (BOS) patients following hematopoietic stem cell transplantation (HSCT) were studied.
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 \[Filipovich AH et al. Biol Blood Marrow Transplant 2005; 11:945-956\]\[Chien JW et al. Biol Blood Marrow Transplant 2010; 16:S106-S114\].
Participant milestones
| Measure |
Albuterol Plus 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®).
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|---|---|
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Overall Study
STARTED
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17
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Overall Study
COMPLETED
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17
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bronchodilator Responsiveness in Obliterative Bronchiolitis
Baseline characteristics by cohort
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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17 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Age Continuous
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48 years
STANDARD_DEVIATION 12 • n=5 Participants
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Sex: Female, Male
Female
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5 Participants
n=5 Participants
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Sex: Female, Male
Male
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12 Participants
n=5 Participants
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Region of Enrollment
Italy
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17 participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[FEV1, expressed in liters (L), after bronchodilators - FEV1 (L) before bronchodilators/FEV1 (L) before bronchodilators x 100\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Per Cent Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators
Responsives to bronchodilators (n=4)
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14 per cent positive change
Standard Deviation 1
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Per Cent Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators
Unresponsives to bronchodilators (n=13)
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7 per cent positive change
Standard Deviation 5
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PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[FEV1 (L) after bronchodilators - FEV1 (L) before bronchodilators\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Absolute Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators
Responsives to bronchodilators (n=4)
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0.26 absolute positive change (liters)
Standard Deviation 0.06
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Absolute Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators
Unresponsives to bronchodilators (n=13)
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0.12 absolute positive change (liters)
Standard Deviation 0.09
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PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[FVC, expressed in liters (L), after bronchodilators - FVC (L) before bronchodilators/FVC (L) before bronchodilators x 100\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Per Cent Change of Forced Vital Capacity (FVC) After Bronchodilators
Responsives to bronchodilators (n=5)
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24 per cent positive change
Standard Deviation 13
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Per Cent Change of Forced Vital Capacity (FVC) After Bronchodilators
Unresponsives to bronchodilators (n=12)
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2 per cent positive change
Standard Deviation 4
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PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[FVC (L) after bronchodilators - FVC (L) before bronchodilators\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Absolute Change of Forced Vital Capacity (FVC) After Bronchodilators
Responsives to bronchodilators (n=5)
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0.65 absolute positive change (liters)
Standard Deviation 0.37
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Absolute Change of Forced Vital Capacity (FVC) After Bronchodilators
Unresponsives to bronchodilators (n=12)
|
0.07 absolute positive change (liters)
Standard Deviation 0.15
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PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[V'max, expressed in liters.second-1 (L.s-1), after bronchodilators - V'max (L.s-1) before bronchodilators/V'max (L.s-1) before bronchodilators x 100\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Per Cent Change of Instantaneous Maximal Forced Expiratory Flow (V'Max) After Bronchodilators
Responsives to bronchodilators (n=4)
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66 per cent positive change
Standard Deviation 17
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Per Cent Change of Instantaneous Maximal Forced Expiratory Flow (V'Max) After Bronchodilators
Unresponsives to bronchodilators (n=13)
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14 per cent positive change
Standard Deviation 14
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PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[V'part, expressed in liters.second-1 (L.s-1), after bronchodilators - V'part (L.s-1) before bronchodilators/V'part (L.s-1) before bronchodilators x 100\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Per Cent Change of Partial Forced Expiratory Flow (V'Part) After Bronchodilators
Responsives to bronchodilators (n=9)
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59 per cent positive change
Standard Deviation 26
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Per Cent Change of Partial Forced Expiratory Flow (V'Part) After Bronchodilators
Unresponsives to bronchodilators (n=8)
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17 per cent positive change
Standard Deviation 7
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PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[RV, expressed in liters (L), before bronchodilators - RV (L) after bronchodilators/RV (L) after bronchodilators x 100\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Per Cent Change of Residual Volume (RV) After Bronchodilators
Responsives to bronchodilators (n=8)
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19 per cent negative change
Standard Deviation 5
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Per Cent Change of Residual Volume (RV) After Bronchodilators
Unresponsives to bronchodilators (n=9)
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0 per cent negative change
Standard Deviation 5
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PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[RV (L), before bronchodilators - RV (L) after bronchodilators\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Absolute Change of Residual Volume (RV) After Bronchodilators
Responsives to bronchodilators (n=8)
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0.65 absolute negative change (liters)
Standard Deviation 0.37
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Absolute Change of Residual Volume (RV) After Bronchodilators
Unresponsives to bronchodilators (n=9)
|
0.00 absolute negative change (liters)
Standard Deviation 0.10
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PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[FRC, expressed in liters (L), before bronchodilators - FRC (L) after bronchodilators/FRC (L) after bronchodilators x 100\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
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|---|---|
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Per Cent Change of Functional Residual Capacity (FRC) After Bronchodilators
Responsives to bronchodilators (n=4)
|
16 per cent negative change
Standard Deviation 6
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Per Cent Change of Functional Residual Capacity (FRC) After Bronchodilators
Unresponsives to bronchodilators (n=13)
|
2 per cent negative change
Standard Deviation 5
|
PRIMARY outcome
Timeframe: Baseline and 90 min after bronchodilatorsPopulation: 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).
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: \[FRC (L), before bronchodilators - FRC (L) after bronchodilators\].
Outcome measures
| Measure |
Albuterol Plus Tiotropium
n=17 Participants
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®).
|
|---|---|
|
Absolute Change of Functional Residual Capacity (FRC) After Bronchodilators
Unresponsives to bronchodilators (n=13)
|
0.07 absolute negative change (liters)
Standard Deviation 0.16
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|
Absolute Change of Functional Residual Capacity (FRC) After Bronchodilators
Responsives to bronchodilators (n=4)
|
0.78 absolute negative change (liters)
Standard Deviation 0.34
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Adverse Events
Albuterol Plus Tiotropium
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. Giovanni Barisione, MD
Azienda Ospedaliera Universitaria San Martino, Genova, Italy
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place