Tiotropium and exercise training in COPD patients: Effects on dyspnea and exercise tolerance

Abstract

Background: Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD). Tiotropium 18 μg once daily induces sustained bronchodilation throughout the day and reduces hyperinfl ation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients. Aim: To determine whether tiotropium enhances the effects of exercise training in patients with COPD. Design: Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study. Setting: Twelve Italian Pulmonary Units practicing pulmonary rehabilitation. Patients and intervention: Two hundred thirty four COPD patients (196 males; mean age: 67.4 ± 7.6; forced expiratory volume at 1 second (FEV 1 ): 41.4 ± 13.0% predicted) were randomised to tiotropium 18 μg or placebo inhalation capsules taken once daily. Both groups underwent a 8 week pulmonary rehabilitation program (PR) consisting of 3 exercise training session per week. Measurements: Baseline, at the end of PR and after 12 weeks, patients completed pulmonary function testing, six minute walking test (6MWT), the Baseline and Transition Dyspnea Index (BDI and TDI), and the St. George's Respiratory Questionnaire (SGRQ). Results: Relative to placebo, tiotropium had larger trough and post-study drug FEV 1 responses on all test days. At the end of and 12 weeks following PR, patients on tiotropium showed no statistically signifi cant differences in 6MWT compared to patients on placebo. Compared to the period immediately prior to PR, the mean improvement in 6MWT was only 29.7 meters (7.1%) for the combined cohort. Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo (p Ͻ 0.01). At 12 weeks after PR, TDI focal scores were 2.71 for tiotropium and 2.11 for placebo (p = 0.16). Reduction in all four SGRQ component scores, indicating an improvement in health-related quality of life, was observed for the tiotropium group over the duration of the study compared to placebo but the differences were not statistically signifi cant. During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group. Conclusion: Although signifi cant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT.

Effect of tiotropium on quality of life in COPD: a systematic review

“…Compared with placebo, a statistically significant improvement in mean SGRQ total score was seen with tiotropium in the 4-year Understanding Potential LongTerm Impacts on Function with Tiotropium (UPLIFT ® ) trial 60 and other studies lasting six months to one year. 51,54,62,73 Shorterterm studies were less consistent in terms of SGRQ total score; a 12-week study 65 concurred with the significant findings of the longer-term trials, but 25-week studies using concurrent pulmonary rehabilitation 50,52 found no significant difference between tiotropium and placebo. The improvement in mean SGRQ total score did not reach the level of clinically meaningful change (-4 units; Table 4) in the majority of these trials; however, significantly more patients achieved this improvement with tiotropium than with placebo.…”

“…[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] Of the 24 publications that met the inclusion criteria for this systematic review (see Table 1), 16 compared tiotropium with placebo, [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] seven compared tiotropium with an active comparator, [66][67][68][69][70][71][72] and one compared tiotropium with both placebo and an active comparator. 73 The QoL outcomes reported in the 24 included publications were mostly SGRQ and/or TDI (Tables 2 and 3).…”

“…51 This benefit of tiotropium on SGRQ total score was reflected in significant improvements in all three SGRQ domains, 51,62 or two domains (symptoms and impact); 54 the difference in another study did not reach statistical significance. 50 Although a clinically significant improvement of -4 units in SGRQ total score compared with placebo was not observed in the full cohort in the UPLIFT ® trial (range, -2.3 to -3.3 units), 60 it is notable that both statistically and clinically significant changes occurred in the GOLD Stage II patient subgroup (range, -2.7 to -4.0 units), 55 patients not receiving maintenance therapy at baseline (-4.6 units at 4 years), 64 and continuing smokers (-4.6 units at 4 years). 61 In terms of SGRQ domains (where reported), symptom and activity domains were improved in GOLD Stage II patients (up to -4.1 and -4.4 units, respectively) 55 and all three domains (impact, symptom, and activity) improved in continuing smokers (-4.2, -4.7, -5.7 units respectively).…”

Tratamento farmacológico da DPOC

“…Most of the analyses of the effect of LAMAsinvolving patients with moderate to severe COPD, as determined by the GOLD classification-have suggested that LAMAs reduce the number of exacerbations or increase the interval between episodes of exacerbation. Two groups of authors (41,42) found no beneficial effects, which might be due to the inclusion of patients with only one episode of exacerbation in the previous year or to greater losses to follow-up in the open to debate. Combination therapy with the three classes of medications apparently leads to greater functional improvement than does the use of each class of medication in isolation.…”

“…In 6 analyses of patients with moderate to very severe COPD, the use of LAMAs was shown to have a beneficial effect on quality of life when compared with the use of a placebo. (9,26,35,41,53,54) However, two groups of authors (11,42) evaluated patients with mild to moderate COPD, as determined by the GOLD classification, and found no such effect. Only one study evaluated the effect of the LAMA-IC combination on quality of life, and it was shown to be superior to that of placebo during the six-month study period.…”