Clinical trial NCT01112241: Bronchodilator Responsiveness in Obliterative Bronchiolitis
Official title: Acute Bronchodilator Responsiveness in Obliterative Bronchiolitis (OB) Following Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obliterative Bronchiolitis
Keywords: Obliterative bronchiolitis
Bronchodilator responsiveness
Partial forced expiratory flow
Lung volumes
Lead sponsor: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Sponsor class: OTHER
First posted: 2010-04-28
Enrollment: 17
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Per Cent Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
measure: Absolute Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
measure: Per Cent Change of Forced Vital Capacity (FVC) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
measure: Absolute Change of Forced Vital Capacity (FVC) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
measure: Per Cent Change of Instantaneous Maximal Forced Expiratory Flow (V'Max) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
measure: Per Cent Change of Partial Forced Expiratory Flow (V'Part) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
measure: Per Cent Change of Residual Volume (RV) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
measure: Absolute Change of Residual Volume (RV) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
measure: Per Cent Change of Functional Residual Capacity (FRC) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
measure: Absolute Change of Functional Residual Capacity (FRC) After Bronchodilators
timeFrame: Baseline and 90 min after bronchodilators
Secondary outcomes:
Other outcomes:
Locations:
city: Genoa
country: Italy
facility: Unit of Preventive and Occupational Medicine - Laboratory of Respiratory Pathophysiology, University Hospital San Martino
Study officials:
affiliation: Unit of Preventive and Occupational Medicine, University Hospital San Martino, Genoa, Italy
name: Giovanni Barisione, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
citation: 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.