tiotropium-bromide and Hyperventilation

Novel evaluation of protective effect of tiotropium against induced dynamic hyperinflation (DH) during metronome paced hyperventilation (MPH) in moderate COPD.. Prospective, randomized, double-blind, placebo control, crossover study. Lung function measured pre/post MPH at 30 breaths/min for 20 s in 29 (18 M) COPD patients (GOLD Stage 2) age 70±9 yr (mean ± SD) before and after 30 days of 18 μg tiotropium bromide vs placebo. Lung CT scored for emphysema (ES).. At baseline post 180 μg aerosolized albuterol sulfate, FEV(1): 1.8±0.6 L (69±6% pred) and ≥60% predicted in all, and 14 of 29 had FEV(1) (L) ≥70% predicted with FEV(1)/FVC 58±8%. After 29 days + 23 h post tiotropium (trough) there was significant decrease only in FRC/TLC% (p=0.04); after 30 days + 2 h post tiotropium (peak) significant increase only in FEV(1) (L) (p=0.03) compared to placebo. Results post MPH induced DH at baseline and after 30 days and 2 h post placebo or tiotropium were similar with decrease in IC 0.44±0.06 L (p<0.001). Correlation between ES and increased FEV(1) (L) at peak tiotropium: r=0.19, p=0.96 and decreased FRC/TLC% at trough tiotropium: r=-0.26, p=0.36.. In moderate COPD, tiotropium did not reduce MPH induced DH and reduction in IC. However, at peak tiotropium, there was significant bronchodilation in FEV(1) (L) and at trough a decrease in FRC/TLC% compared to placebo despite varying emphysema.

Topics: Aged; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hyperventilation; Male; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide; Tomography, X-Ray Computed

Hyperinflation is widely accepted as an abnormal state affecting clinical symptoms, activities of daily living and exercise tolerance in chronic obstructive pulmonary disease (COPD). Reducing hyperinflation is an essential theme in COPD treatment. In this study, we let patients with COPD hyperventilate to evoke hyperinflation, and evaluated the effects of tiotropium alone or in combination with salmeterol on hyperventilation-evoked hyperinflation.. Thirty-eight patients with COPD received pulmonary function tests including hyperventilation-evoked hyperinflation testing and the St. George's Respiratory Questionnaire (SGRQ) before treatment, after tiotropium administration for 8 weeks, and after combined therapy with salmeterol for 8 weeks.. Before treatment, inspiratory capacity (IC) after hyperventilation decreased significantly in a breathing frequency-dependent manner. After tiotropium administration, forced expiratory volume in one second (FEV1) increased significantly. IC after hyperventilation decreased significantly in a breathing frequency-dependent manner; however, IC was significantly greater than that before treatment (at rest, p=0.001; after hyperventilation at twice the resting respiratory rate, p=0.0009; and after hyperventilation at three times the resting respiratory rate, p<0.0001). The SGRQ score also improved significantly. After combined therapy with salmeterol, FEV1 increased significantly compared with after tiotropium alone. However, there was no significant difference between the IC after tiotropium alone and that after combined therapy, at each stage. However, after combined therapy the SGRQ score significantly improved compared with that after tiotropium alone.. Tiotropium improved airflow obstruction and hyperventilation-evoked hyperinflation. In combination with salmeterol, the improvement in airflow obstruction was greater, but hyperventilation-evoked hyperinflation was not further improved.

Topics: Aged; Albuterol; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Hyperventilation; Inspiratory Capacity; Lung; Lung Volume Measurements; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

The magnitude of tiotropium (1) induced bronchodilation and (2) protection against dynamic hyperinflation in COPD phenotypes has not been studied.. We studied moderate to severe COPD patients with varying extent of emphysema as evaluated by high-resolution thin-section lung CT. Spirometry including inspiratory capacity (IC) was measured before and immediately after metronome paced hyperventilation (MPH) at 2 times resting respiratory rate for 20s to induce dynamic hyperinflation. Spirometry was obtained at baseline and pre- and 1.5h post-18 microg tiotropium via HandiHaler after 30 day tiotropium treatment period in a single blind, open label intervention.. In 29 COPD patients (15M), age 70+/-9 years (mean+/-SD) with smoking history of 53+/-37 pack years, baseline forced expiratory volume in 1s (FEV(1)) post-180 microg albuterol MDI was 1.6+/-0.4 L (61+/-8% predicted) and FEV(1)/FVC 59+/-6%. Lung CT emphysema score (LCTES) was 23+/-20 (mean+/-SD) on a scale of 0-100 (none to most severe emphysema). After 30-day tiotropium, FEV(1) increased 101+/-124 mL (mean+/-SD) (p<0.001) and Spearman correlation (r)=-0.04, p=0.8 with LCTES; IC increased 163+/-232 mL (p<0.001), and r=-0.2, p=0.3 with LCTES. Results following MPH induced DH before and after 30-day tiotropium were significant (p<0.001) and similar: IC decreased 340+/-280 mL before and 337+/-270 mL after tiotropium, and r=-0.3, p=0.9 with LCTES.. Tiotropium significantly increased FEV(1) (L) and inspiratory capacity in moderate-severe COPD, independent of extent of lung CT emphysema score. Despite bronchodilation and lower resting lung volume, tiotropium did not abbreviate induced dynamic hyperinflation, which was also independent of underlying emphysema.

Topics: Aged; Bronchodilator Agents; Female; Forced Expiratory Volume; Humans; Hyperventilation; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Respiratory Function Tests; Scopolamine Derivatives; Smoking; Tiotropium Bromide; Tomography, X-Ray Computed; Vital Capacity

To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium.. IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH.. At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/- 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003).. In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.

Topics: Aged; Albuterol; Bronchodilator Agents; Female; Forced Expiratory Volume; Functional Residual Capacity; Humans; Hyperventilation; Inspiratory Capacity; Male; Middle Aged; Plethysmography, Whole Body; Pulmonary Disease, Chronic Obstructive; Residual Volume; Scopolamine Derivatives; Smoking; Spirometry; Tiotropium Bromide; Total Lung Capacity; Treatment Outcome; Vital Capacity