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Original Research: OBSTRUCTIVE LUNG DISEASES |

Acute Bronchodilator Responsiveness in Bronchiolitis Obliterans Syndrome Following Hematopoietic Stem Cell Transplantation

Giovanni Barisione, MD; Andrea Bacigalupo, MD; Emanuele Crimi, MD; Vito Brusasco, MD
Author and Funding Information

From the Unità Operativa Medicina Preventiva e del Lavoro (Dr Barisione), Laboratorio di Fisiopatologia Respiratoria; Unità Operativa Ematologia 2 (Dr Bacigalupo), Azienda Ospedaliera Universitaria “San Martino”; and Unità Operativa Fisiopatologia Respiratoria (Drs Crimi and Brusasco), Dipartimento di Medicina Interna, Università di Genova, Italy.

Correspondence to: Giovanni Barisione, MD, Unità Operativa Medicina Preventiva e del Lavoro, Laboratorio di Fisiopatologia Respiratoria, Azienda Ospedaliera Universitaria “San Martino,” Largo Rosanna Benzi, 10, 16132 Genova, Italy; e-mail: giovanni.barisione@hsanmartino.it


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

Funding/Support: This study was supported by the Associazione Italiana Ricerca contro il Cancro (AIRC), Milano, Italy.


© 2011 American College of Chest Physicians


Chest. 2011;139(3):633-639. doi:10.1378/chest.10-1442
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Background:  The obstructive abnormality of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is deemed to be virtually insensitive to treatment with inhaled bronchodilators. We studied whether nonconventional assessment of bronchodilation may help to detect physiologically meaningful airway responses missed by traditional criteria.

Methods:  Standard spirometry, partial and maximal expiratory flow-volume curves, and lung volumes were measured before and 90 min after inhalation of albuterol plus tiotropium in 17 patients who developed mild to very severe BOS following HSCT.

Results:  After treatment with bronchodilators, the standard criteria of reversibility based on FEV1 and FVC were met in seven out of 17 patients. In eight patients, residual volume (RV) decreased beyond its within-session spontaneous variability, and functional residual capacity (FRC) was reduced in four of them. Partial forced expiratory flow (V˙ part) increased beyond its within-session spontaneous variability in nine patients. Out of 10 patients in whom neither FEV1 nor FVC met the standard criteria of reversibility, six had a positive increase in V˙ part or a decrease of lung hyperinflation (ie, FRC) or RV. In six patients with limited expiratory flow during tidal breathing, the postbronchodilator increase in V˙ part was correlated with a decrease in FRC (R2 = 0.83; P = .011).

Conclusions:  This study suggests that airway smooth muscle tone plays a significant role in BOS after HSCT and that the common knowledge of BOS as an irreversible obstructive disease may stem from the limitation of simple spirometry to detect changes in small airways.

Trial registry:  ClinicalTrials.gov; No.: NCT01112241 (BOS-01); URL: www.clinicaltrials.gov

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