Bronchodilator Responsiveness in Obliterative Bronchiolitis (BD-OB)

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

Status and phase: Completed; Phase 4

Conditions: Obliterative Bronchiolitis

Treatments: Drug: albuterol plus tiotropium

Study type: Interventional

Funder types: Other

Identifiers

NCT01112241

BOS-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 17 patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

17 participants in 1 patient group

albuterol-tiotropium

Experimental 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®).

Treatment:

Drug: albuterol plus tiotropium