tiotropium-bromide and Bronchiolitis-Obliterans

Patients with postinfectious bronchiolitis obliterans (PIBO) usually have severe airflow obstruction and respond poorly to β-adrenergic drugs. However, the bronchodilator response to an anticholinergic agent such as tiotropium bromide is not known. We studied the acute bronchodilator response to tiotropium for up to 24 h in children with PIBO using spirometric and plethysmographic criteria.. A randomized, double-blind, placebo-controlled, crossover, prospective study was performed in patients with stable PIBO, 6 to 16 years of age. Standard spirometry and plethysmography were performed before and at 30, 60, 120, and 180 min and 24 h after inhalation of 18 μg of tiotropium or a placebo. After 7 to 14 days, the drugs were inverted, and the procedures were repeated. The changes in lung function parameters at each time point were compared with the baseline by analysis of variance and Tukey posttest, and the differences in all time points assessments vs baseline in tiotropium vs placebo groups were compared using the Friedman test.. A total of 30 patients were enrolled in the study (23 boys, seven girls; aged 10.9 ± 2.8 years) with baseline lung function values (% predicted) of FVC, FEV1, FEV1/FVC, forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), total lung capacity (TLC), residual volume (RV), RV/TLC, airway resistance (Raw), and specific airway conductance (sGaw) of 75 ± 15, 48 ± 14, 59 ± 11, 22 ± 11, 120 ± 19, 281 ± 101, 49 ± 13, 250 ± 65, and 23 ± 9, respectively. Statistically significant differences were observed after tiotropium inhalation in the following parameters compared with baseline: FVC at 60, 120, and 180 min and 24 h; FEV1 at 30, 60, 120, and 180 min; FEV1/FVC at 60, 120, and 180 min; FEF25%-75% at 60, 120, and 180 min; RV at 30, 60, 120, and 180 min; TLC at 30, 120, and 180 min; RV/TLC at 30, 60, 120, and 180 min; Raw at 30, 60, 120, and 180 min and 24 h; and sGaw at 30, 60, 120, and 180 min and 24 h. For the placebo group, no significant differences were observed in any lung function parameters at any time. The differences in the main functional measurements between the tiotropium and placebo groups were statistically significant.. Tiotropium acutely decreased airway obstruction and air trapping for up to 24 h in children with PIBO.

Topics: Administration, Inhalation; Bronchiolitis Obliterans; Bronchoconstriction; Bronchodilator Agents; Child; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Plethysmography; Prospective Studies; Respiratory Function Tests; Respiratory Tract Infections; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS.. Post-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled.. Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group.. Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.

Topics: Bronchiolitis Obliterans; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Hematopoietic Stem Cell Transplantation; Humans; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Tiotropium Bromide

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

Topics: Administration, Inhalation; Adult; Albuterol; Bronchiolitis Obliterans; Bronchodilator Agents; Drug Resistance; Female; Forced Expiratory Volume; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Muscle, Smooth; Retrospective Studies; Scopolamine Derivatives; Spirometry; Tiotropium Bromide; Vital Capacity

A 48-year-old woman was admitted with dyspnea on effort. She suffered from adult T-cell leukemia and received peripheral blood stem cell transplantation (PBSCT). Eight months after the PBSCT, she developed dyspnea on effort and was treated with bronchodilator, inhaled corticosteroid, anti-leukotriene drug, theophylline and oxytropium bromide. However her symptoms progressed and she was admitted. We diagnosed bronchiolitis obliterans syndrome (BOS) because of obstructive pulmonary dysfunction, diffuse patchy high density of the lung field on chest computed tomography and decreased ventilation with peripheral patchy accumulation on ventilation scintigraphy. She was treated with corticosteroid and cyclosporine A and her symptoms and her pulmonary function were improved. However, in parallel with corticosteroid tapering, her symptoms and pulmonary functions worsened. Treatment with Tiotropium bromide was started and her pulmonary function improved significantly. Her pulmonary function did not worsen and tapering steroid dose was successfully achieved. PBSCT was reported to up-regulate the muscarinic receptor activity in lung. Tiotropium bromide might become one additional option for the treatment of BOS.

Topics: Bronchiolitis Obliterans; Bronchodilator Agents; Drug Administration Schedule; Female; Humans; Leukemia-Lymphoma, Adult T-Cell; Middle Aged; Remission Induction; Scopolamine Derivatives; Tiotropium Bromide