Acute bronchodilator responsiveness in bronchiolitis obliterans syndrome following hematopoietic stem cell transplantation.
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 (Vpart) 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 Vpart or a decrease of lung hyperinflation (ie, FRC) or RV. In six patients with limited expiratory flow during tidal breathing, the postbronchodilator increase in Vpart 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.


BACKGROUND
ClinicalTrials.gov; No.: NCT01112241 (BOS-01); URL: www.clinicaltrials.gov.
Barisione
Giovanni
G
Unità Operativa Medicina Preventiva e del Lavoro, Laboratorio di Fisiopatologia Respiratoria, Italy. Electronic address: giovanni.barisione@hsanmartino.it.
Bacigalupo
Andrea
A
Unità Operativa Ematologia 2, Azienda Ospedaliera Universitaria "San Martino", Italy.
Crimi
Emanuele
E
Unità Operativa Fisiopatologia Respiratoria, Dipartimento di Medicina Interna, Università di Genova, Italy.
Brusasco
Vito
V
Unità Operativa Fisiopatologia Respiratoria, Dipartimento di Medicina Interna, Università di Genova, Italy.
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D012189:Retrospective Studies; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013147:Spirometry; D000069447:Tiotropium Bromide; D014797:Vital Capacity / Q000187:drug effects
D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000420:Albuterol; D000069447:Tiotropium Bromide