Transition Dyspnea Index Research Articles

P148 Correlating changes in lung function with patient reported outcomes in COPD

IntroductionRelationships between improvements in lung function and other outcomes in COPD patients are not documented extensively. We examined the association between changes in FEV1 and patient-centred outcomes using pooled data...

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

Chronic obstructive pulmonary disease (COPD) greatly affects quality of life (QoL). Although QoL is a key concern for the patient, primary endpoints in most clinical trials are objective measures of disease progression. A systematic review of double-blind randomised controlled trials was undertaken to identify data relating to the effect of tiotropium on QoL in patients with COPD. A total of 24 publications met the inclusion criteria. Compared with placebo, in the majority of studies tiotropium statistically significantly improved the St George's Respiratory Questionnaire (SGRQ) total score, although improvement beyond the accepted minimum clinically important difference (MCID) of 4 units was only achieved in three studies, all of which were of less than nine months' duration. Tiotropium also statistically significantly improved the Transition Dyspnoea Index (TDI) focal score, equating to clinically meaningful improvements, in almost all the studies that assessed TDI. In general, higher proportions of patients receiving tiotropium achieved clinically meaningful responses. The addition of other therapies (dual therapy, triple therapy) to tiotropium provided benefits that exceeded the SGRQ MCID and provided further benefit with regard to the TDI. Tiotropium improves QoL for patients with COPD requiring long-acting bronchodilators, with other additional therapies providing further benefits, depending on the population.

A Randomized Pilot Study of Acupuncture as an Adjunct Therapy in Adult Asthmatic Patients

Objective. This trial aimed to evaluate the feasibility of estimating the effectiveness of acupuncture on asthmatic patients under conventional medical management. Participations and Methods. A prospective randomized, patient/assessor-blinded, sham acupuncture–, and waiting list–controlled pilot trial was conducted. Forty-five eligible asthmatic participants underwent a 1-week run-in period and were then randomized into one of three groups: an active acupuncture group, a sham acupuncture group, and a waiting list group. They were instructed to maintain the use of antiasthmatic medications. Needling was administered three times per week for 4 weeks with a 2-week follow-up in the active and sham acupuncture groups. The primary outcome was daily morning peak expiratory flow (PEF) and the secondary outcomes included forced expiratory volume one second (FEV1), quality of life questionnaire for adult Korean asthmatics (QLQAKA), transition dyspnea index (TDI), serum eosinophil count, and total serum immunoglobulin E (IgE). Results. No significant differences in the between- or within-group values of weekly average PEF (recorded daily in the morning) and FEV1 were found. For QLQAKA and TDI, the active acupuncture group showed a significant improvement over the waiting list group at 2, 4, and 6 weeks after randomization. Discussion. Acupuncture as an adjunct therapy to conventional medical care does not seem to affect pulmonary function in asthmatic patients. However, 12 sessions of acupuncture treatment during 4 weeks showed a favorable effect on the quality of life in adult asthmatic patients. Further large trials assessing the effectiveness of acupuncture on the quality of life and symptoms in asthmatic patients are needed.

Once-daily indacaterolversustwice-daily salmeterol for COPD: a placebo-controlled comparison

Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β(2)-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily β(2)-agonist, salmeterol, as an active control. Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 μg once daily), salmeterol (50 μg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV(1)) after 12 weeks. 1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV(1) at week 12 by 170 mL over placebo (p<0.001) and by 60 mL over salmeterol (p<0.001). Both active treatments improved health status (St George's Respiratory Questionnaire) and dyspnoea (transition dyspnoea index) compared with placebo, with differences between them favouring indacaterol. Safety profiles were similar across the treatment groups, and both indacaterol and salmeterol were well tolerated. Once-daily treatment with 150 μg indacaterol had a significant and clinically relevant bronchodilator effect over 24 h post-dose and improved health status and dyspnoea to a greater extent than twice-daily 50 μg salmeterol. Indacaterol should prove a useful additional treatment for patients with COPD.

Efficacy of a new once-daily long-acting inhaled β2-agonist indacaterol versus twice-daily formoterol in COPD

BackgroundIndacaterol is a long-acting inhaled β2-agonist (LABA) for the treatment of chronic obstructive pulmonary disease (COPD). In previous studies, indacaterol provided 24 h bronchodilation on once-daily dosing with a fast...

Efficacy and safety of tiotropium Respimat&amp;reg; SMI in COPD in two 1-year randomized studies

Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 microg versus placebo, inhaled via the Respimat Soft Mist Inhaler (SMI). The two studies were combined and had 4 co-primary endpoints (trough FEV(1) response, Mahler Transition Dyspnea Index [TDI] and St George's Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year). A total of 1990 patients with COPD participated (mean FEV(1): 1.09 L). The mean trough FEV(1) response of tiotropium 5 or 10 microg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001). The COPD exacerbation rate was significantly lower with tiotropium 5 microg (RR = 0.78; P = 0.002) and tiotropium 10 microg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001). Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment. Fatal events occurred in 2.4% (5 microg), 2.7% (10 microg), and 1.6% (placebo) of patients; these differences were not significant. Tiotropium Respimat SMI 5 microg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 microg dose but with a lower frequency of anticholinergic adverse events.

Once-Daily Bronchodilators for Chronic Obstructive Pulmonary Disease

Indacaterol is the first once-daily, long-acting inhaled beta(2)-agonist bronchodilator studied in patients with chronic obstructive pulmonary disease (COPD). To demonstrate greater efficacy of indacaterol versus placebo on FEV(1) at 24 hours post dose (trough) after 12 weeks, to compare efficacy with placebo and tiotropium, and to evaluate safety and tolerability over 26 weeks. Patients with moderate-to-severe COPD were randomized to double-blind indacaterol 150 or 300 microg or placebo, or open-label tiotropium 18 microg, all once daily, for 26 weeks. The primary efficacy outcome was trough FEV(1) at 12 weeks. Additional analyses (not adjusted for multiplicity) included transition dyspnea index (TDI), health status (St George's Respiratory Questionnaire [SGRQ]), and exacerbations. Serum potassium, blood glucose, and QTc interval were measured. A total of 1,683 patients (age, 63.3 yr; post-bronchodilator FEV(1), 56% predicted; FEV(1)/FVC, 0.53) were randomized to the four treatment arms. Trough FEV(1) at Week 12 increased versus placebo by 180 ml with both indacaterol doses and by 140 ml with tiotropium (all P < 0.001 vs. placebo). At Week 26, for indacaterol 150/300 microg, respectively, versus placebo, TDI increased (1.00/1.18, P < 0.001) and SGRQ total score decreased (-3.3/-2.4, P < 0.01); corresponding results with tiotropium were 0.87 (P < 0.001) for TDI and (-1.0, P = not significant) for SGRQ total score. The incidence of adverse events, low serum potassium, high blood glucose, and prolonged QTc interval was similar across treatments. Indacaterol was an effective once-daily bronchodilator and was at least as effective as tiotropium in improving clinical outcomes for patients with COPD. Clinical trial registered with clinicaltrials.gov (NCT 00463567).

Patient-Reported Dyspnea in COPD Reliability and Association With Stage of Disease

Although questionnaires are used frequently with patients to self-report the severity of dyspnea as related to activities of daily living, the reliability of these instruments has not been established. The two purposes of this study were to examine the test-retest reliability of three widely used dyspnea instruments and to compare dyspnea scores at different stages of disease. At paired baseline visits, 101 stable patients with COPD were tested; at paired follow-up visits at 3 months, 89 of these patients were tested. At each visit, patients rated dyspnea with three instruments presented in random order and then performed post-bronchodilator therapy lung function tests. Patient-reported dyspnea scores and lung function were similar at baseline (interval, 6 +/- 5 days) and follow-up visits (interval, 4 +/- 2 days). Intraclass correlation coefficients at baseline and at follow-up were 0.82 and 0.82, respectively, for the modified Medical Research Council scale; 0.90 and 0.84, respectively, for the self-administered computerized versions of the baseline dyspnea index and transition dyspnea indexes; and 0.95 and 0.89 for the University of San Diego Shortness of Breath Questionnaire results. Dyspnea ratings were significantly related to the stage of disease severity based on percent predicted FEV(1) (p < 0.001). Test-retest reliability was acceptable for patient-reported dyspnea scores using three clinical instruments at baseline and at the 3-month follow-up. Our results demonstrate for the first time that patient-reported dyspnea ratings are related to the stage of disease severity.

Nebulized formoterol provides added benefits to tiotropium treatment in chronic obstructive pulmonary disease

The use of one or more long-acting bronchodilators is key in the maintenance therapy of chronic obstructive pulmonary disease (COPD). This analysis pooled the results of two double-blind studies evaluating the efficacy and safety of adding nebulized formoterol fumarate inhalation solution (FFIS) to maintenance tiotropium (TIO) treatment. Following a run-in period of 7-14 days with once-daily TIO 18 microg, COPD subjects (> or =25% to <65% predicted forced expiratory volume in 1 second [FEV(1)]) were randomized to twice-daily FFIS 20 microg (n=145) or nebulized placebo (PLA, n=140) while continuing on maintenance TIO for 6 weeks. Efficacy was measured using serial spirometry, transition dyspnea index (TDI), rescue albuterol use, and St. George's Respiratory Questionnaire (SGRQ). The mean standardized area under the curve for FEV(1) over 3 hours (FEV(1)AUC(0-3)), the primary efficacy variable, was significantly higher in the FFIS/TIO group than the PLA/TIO group on day 1 (140 mL difference, P<0.0001) and week 6 (192 mL difference, P<0.0001). Mean TDI scores in the FFIS/TIO and PLA/TIO groups were 1.97 and 0.67, respectively (P=0.0001). Mean albuterol use declined in the FFIS/TIO group from 2.6 to 1.5 puffs/day compared with little change in the PLA/TIO group (P<0.0001). SGRQ scores were similar between treatment groups with the exception of the symptoms score, which improved in the FFIS/TIO group (-5.8) compared with PLA/TIO (-1.0), and more FFIS/TIO-treated subjects experienced a clinically significant improvement in total SGRQ score. More PLA/TIO-treated subjects than FFIS/TIO-treated subjects experienced adverse events (AEs) (45.7% vs. 31.0%) and COPD exacerbations (7.9% vs. 3.4%). The addition of FFIS to maintenance TIO treatment for moderate to severe COPD results in significantly improved FEV(1) and dyspnea, decreased rescue medication use, and a lower incidence of AEs and COPD exacerbations. The addition of FFIS to TIO yields clinically and statistically significant benefits for COPD patients and might be of long-term benefit.

Minimally important differences in the Mahler's Transition Dyspnoea Index in a large randomized controlled trial--results from the Scleroderma Lung Study

Scleroderma Lung Study (SLS) showed that cyclophosphamide (CYC) was better than placebo (PLA) in preventing progression of forced vital capacity percentage (FVC%) predicted and dyspnoea at 12 months. Our objective was to assess minimally important difference (MID) for Mahler's Transition Dyspnoea Index (TDI) in SLS. A total of 158 subjects participated in the SLS. Data from the two treatment groups were combined for this analysis. We used five patient-reported anchors from the short form (SF)-36 instrument to assess MID for TDI-SF-36 transition question and four questions from SF-36 pertaining to walking on a flat surface or climbing stairs. On the SF-36 transition question, patients who rated as a little better or a little worse were defined as the MID subgroup. For other questions, patients who reported improvement from 'Limited a lot' to 'Limited a little' and 'Limited a little' to 'No limit' and vice versa were defined as the MID subgroup. The MID estimates for the TDI improvement and worsening ranged from 1.05 to 2.16 (mean score = 1.5) U and from -0.61 to -2.55 (mean score = -1.5) U, respectively. Change in this group was larger than that of the no-change group (mean score = 0.38 U). Patients who achieved the MID for improvement at 12 months had a greater improvement in their FVC% predicted (3.6%) compared with those who did not (-3.3%; P < 0.001). A change (improvement/worsening) of 1.5 U in the TDI is the MID for SSc-related interstitial lung disease (SSc-ILD). This can aid in interpreting clinically important changes in breathlessness in SSc-ILD.

Quality of life and dyspnoea in patients treated with bosentan for idiopathic pulmonary fibrosis (BUILD-1)

No therapy is known to improve health-related quality of life (HRQoL) or dyspnoea in patients with idiopathic pulmonary fibrosis. The present study investigated longitudinal changes in HRQoL and dyspnoea and explored the effects of bosentan on these end-points during the Bosentan Use in Interstitial Lung Disease (BUILD)-1 trial. In total, 154 subjects received oral bosentan (n = 71) or placebo (n = 83). Changes in HRQoL and dyspnoea from baseline to month (M) 6 and up to M12 were measured using the St George's Respiratory Questionnaire (SGRQ), 36-item short-form health survey (SF-36), Transition Dyspnoea Index and Borg dyspnoea index. Overall, minimal changes occurred in measures of HRQoL and dyspnoea among placebo-treated subjects during the study. The effects of bosentan treatment on HRQoL and dyspnoea in the all-treated population were minimal. However, in the subset of subjects who had undergone surgical lung biopsy for diagnosis of idiopathic pulmonary fibrosis, treatment effects were observed up to M12 in the impact domain of the SGRQ and the physical functioning, general health and role emotional domains of the SF-36. HRQoL and dyspnoea changed minimally during the course of the present study. Observations from exploratory analyses suggested benefits of bosentan on HRQoL among patients who had undergone surgical lung biopsy for diagnosis, and they merit further investigation.

Evaluation of withdrawal of maintenance tiotropium in COPD

In chronic diseases such as chronic obstructive pulmonary disease (COPD), patients may not perceive all of the benefits of drug therapy until withdrawal. Thus, we evaluated the effect of tiotropium withdrawal on clinical variables. COPD subjects who participated in two identical 1-year, prospective, double-blind, placebo-controlled studies of tiotropium 18 microg once daily who completed a 3-week visit following discontinuation of therapy were included in this analysis. Outcomes measured included dyspnea (transition dyspnea index [TDI]), Peak Expiratory Flow Rate (PEFR), health status (St George's Respiratory Questionnaire [SGRQ]), and rescue beta2-agonist use. Overall, the tiotropium group exhibited significant improvements in clinical parameters at the end of therapy. Of the entire cohort of 921 patients, 713 patients (77%) completed 3-weeks post-withdrawal evaluation. Patients in the tiotropium group had 1.1 unit worsening in TDI, decreased in PEFR, health status and reduced beta(2)-agonist medication following treatment discontinuation, while the placebo group remained relatively stable. The withdrawal of tiotropium results in worsening of COPD over a three-week interval. There was no evidence of a rebound effect in response to tiotropium withdrawal.

Impact of frequency of COPD exacerbations on pulmonary function, health status and clinical outcomes.

COPD exacerbations are responsible for the morbidity and mortality of this disease. The relationship between exacerbations and patient-related clinical outcomes is not clearly understood. A retrospective analysis of two 1-year, placebo-controlled clinical trials with tiotropium 18 microg daily was conducted to examine relationships between exacerbations and other clinical outcomes. The relationship between FEV(1), St. George's Respiratory Questionnaire (SGRQ), and the transition dyspnea index (TDI) were examined based on the frequency of exacerbations (0, 1, 2, >2). 921 patients participated in the trials (mean age 65 years, mean FEV(1) = 1.02 L (39% predicted). The percent change from baseline in FEV(1) in the tiotropium group was +12.6%, +12.0%, +2.1% and +8.9%; and in the placebo group was -3.4%, -3.4%, -5.7% and -6.7% for exacerbation frequencies of 0, 1, 2, >2, respectively. Compared with baseline, the largest improvement in SGRQ occurred in patients with no exacerbations. In the placebo group, there was a significant association between an increased frequency of exacerbations and worsening SGRQ scores. A reduction in exacerbation rates of 4.4% to 42.0% such as that shown in this study cohort was associated with meaningful changes in questionnaire based instruments. In the placebo-treated patients increased frequency of exacerbations was associated with larger decrements in FEV(1), TDI, and SGRQ. A reduction in the frequency of exacerbations is associated with changes that are considered meaningful in these clinical outcomes.

Hospital-at-home care for exacerbations of chronic obstructive pulmonary disease: an observational cohort study of patients managed in hospital or by nurse practitioners in the community

The Urgent Care Team (UCT) in Sunderland (pop. 293,000) is a unique nurse practitioner service operating a hospital at home 24/7/365 to deal promptly with patients suffering an exacerbation of their COPD (AECOPD). Treatment is according to patient group directions utilising nebulised bronchodilators, doxycycline and prednisolone. To compare the health status and pathophysiology during and two months after an AECOPD in 60 UCT patients (31 male) and 30 hospital-managed patients (16 male). The St. Georges Respiratory Questionnaire (SGRQ), Mahler Baseline Dyspnoea Index (BDI) and MRC dyspnoea score recorded health status. Spirometry, BMI and grip strength were also measured. All patients were reviewed 2-3 months after the AECOPD. Changes from BDI were measured using the Transitional Dyspnoea Index (TDI). Mean FEV1% predicted was 47%. In the recovery phase the two groups were comparable for all variables. But during their AECOPD hospitalised patients had a significantly lower BDI (P < 0.05) and an oxygen saturation ranging from 84 to 93% compared with 87-96% for UCT patients. Paired t-tests indicated that on recovery SGRQ activity domain and TDI measures improved in both groups. No deaths occurred during these AECOPDs. A hospital-at-home scheme for AECOPDs can deal with patients who have severe COPD safely. The Mahler TDI appears to be a sensitive index of improvement after an AECOPD.

Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD

Current guidelines support using in combination more than one class of long-acting bronchodilator for COPD patients whose symptoms are not controlled by mono-therapy. This 2-week, multi-center (34 sites), randomized, modified-blind, parallel group study evaluated the efficacy and safety of concomitant treatment with nebulized arformoterol (the formoterol(R,R)-isomer) BID and tiotropium DPI QD. COPD patients (mean FEV(1) 1.37L, 45.4% predicted) were randomized to receive mono-therapy (either arformoterol 15microg BID [n=76] or tiotropium 18microg QD [n=80]), or combined therapy (sequential dosing of arformoterol 15microg BID and tiotropium 18microg QD [n=78]). Changes in pulmonary function, dyspnea, and rescue levalbuterol use were evaluated, as were safety outcomes. Mean FEV(1)AUC(0-24) (the primary endpoint) improved similarly from baseline for arformoterol (0.10L) and tiotropium (0.08L) treatment groups and greater for the combined therapy group (0.22L; all p-values <0.005). Peak FEV(1), peak FVC, 24-h trough FEV(1), and inspiratory capacity also improved similarly for the mono-therapies and greatest for the combined therapy. Dyspnea (mean transition dyspnea index) improved similarly for arformoterol (+2.3) and tiotropium (+1.8) and greatest with combined therapy (+3.1; p-values <0.05). Levalbuterol use decreased for all treatment groups (range -1.8 to -2.5 actuations/day). All treatments had similar frequency of adverse events. In this study, the combination of nebulized arformoterol 15microg BID plus tiotropium 18microg DPI QD was the most effective in improving pulmonary function and disease symptoms. Mono-therapy improvement with arformoterol or tiotropium was similar. All three treatments were well tolerated.

Nebulized formoterol effect on bronchodilation and satisfaction in COPD patients compared to QID ipratropium/albuterol MDI

ABSTRACTObjective: Bronchodilator maintenance treatment improves pulmonary function and health-related quality of life in COPD patients. Pulmonary function and patient preference/satisfaction were compared before and after treatment with a short-acting ipratropium/albuterol combination and long-acting nebulized formoterol.Methods: A randomized, open-label, crossover trial was conducted at 16 centers in the US. COPD subjects (n = 109, 52.8% predicted FEV1) received nebulized formoterol fumarate inhalation solution (Perforomist**, FFIS 20 μg BID) or ipratropium and albuterol combined in a metered-dose inhaler (MDI) (Combivent, IPR-ALB, QID) for 2 weeks. After a 1-week washout, subjects were crossed over to the other treatment. Efficacy was assessed with 6-h pulmonary function tests and the transition dyspnea index (TDI). Treatment satisfaction and preference were assessed after treatment. Post-hoc subgroup analyses were conducted by age, gender and COPD severity.** Perforomist is a registered trademark name of Dey LP, Napa, CA, USA† Combivent is a registered trademark of Boehringer Ingelheim, Ridgefield, CT, USAMain outcome measure: Morning pre-dose FEV1 (trough) after 2 weeks of treatment.Results: FFIS significantly increased morning pre-dose FEV1 relative to IPR-ALB (p = 0.0015). FFIS also improved pre-dose FEV1 beyond that of IPR-ALB in subjects who were older (≥65 years), male, and with both moderate and severe/very severe COPD. Post-dose efficacy at 6 h was maintained in the FFIS group compared with IPR-ALB (p ≤ 0.0001). Patient satisfaction and the perception of disease control were significantly greater with FFIS in the older, male, and severe subgroups. Severe subjects preferred FFIS to IPR-ALB. Both FFIS and IPR-ALB treatments resulted in clinically meaningful changes in dyspnea, but no significant differences were observed between treatments.Conclusions: Following a 2-week treatment period, twice-daily nebulized FFIS was significantly more effective in improving lung function than the IPR-ALB combination MDI delivered four times daily. Although the open-label design may limit interpretation of pulmonary function, the crossover design enabled demonstration of greater treatment satisfaction and perception of disease control following nebulized FFIS treatment.Clinical trial registration: Clinicaltrials.gov NCT00462540

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

Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD). Tiotropium 18 microg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients. To determine whether tiotropium enhances the effects of exercise training in patients with COPD. Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study. Twelve Italian Pulmonary Units practicing pulmonary rehabilitation. Two hundred thirty four COPD patients (196 males; mean age: 67.4 +/- 7.6; forced expiratory volume at 1 second (FEV1): 41.4 +/- 13.0% predicted) were randomised to tiotropium 18 microg 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. 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). Relative to placebo, tiotropium had larger trough and post-study drug FEV1 responses on all test days. At the end of and 12 weeks following PR, patients on tiotropium showed no statistically significant 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 < 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 significant. During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group. Although significant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT.

Inspiratory muscle training in adults with chronic obstructive pulmonary disease: An update of a systematic review

The purpose was to update an original systematic review to determine the effect of inspiratory muscle training (IMT) on inspiratory muscle strength and endurance, exercise capacity, dyspnea and quality of life for adults with chronic obstructive pulmonary disease (COPD). The original MEDLINE and CINAHL search to August 2003 was updated to January 2007 and EMBASE was searched from inception to January 2007. Randomized controlled trials, published in English, with adults with stable COPD, comparing IMT to sham IMT or no intervention, low versus high intensity IMT, and different modes of IMT were included. Nineteen of 274 articles in the original search met the inclusion criteria. The updated search revealed 17 additional articles; 6 met the inclusion criteria, all of which compared targeted, threshold or normocapneic hyperventilation IMT to sham IMT. An update of the sub-group analysis comparing IMT versus sham IMT was performed with 10 studies from original review and 6 from the update. Sixteen meta-analyses are reported. Results demonstrated significant improvements in inspiratory muscle strength (PI(max), PI(max) % predicted, peak inspiratory flow rate), inspiratory muscle endurance (RMET, inspiratory threshold loading, MVV), exercise capacity (Ve(max), Borg Score for Respiratory Effort, 6MWT), Transitional Dyspnea Index (focal score, functional impairment, magnitude of task, magnitude of effort), and the Chronic Respiratory Disease Questionnaire (quality of life). Results suggest that targeted, threshold or normocapneic hyperventilation IMT significantly increases inspiratory muscle strength and endurance, improves outcomes of exercise capacity and one measure of quality of life, and decreases dyspnea for adults with stable COPD.

Lung function and symptom improvement with fluticasone propionate/salmeterol and ipratropium bromide/albuterol in COPD: Response by beta-agonist reversibility

This retrospective analysis of data from two multi-center, randomized, double-blind, parallel group studies compared the efficacy of fluticasone propionate/salmeterol (FSC) 250/50 mcg twice daily with ipratropium bromide/albuterol (IB/ALB) 36/206 mcg four times daily in albuterol-reversible ( n=320 [44%]) and non-reversible ( n=399 [56%]) patients with COPD. In reversible and non-reversible patients, both treatments significantly increased FEV 1AUC 0–6h from baseline and the magnitude of improvement was larger in reversible patients. FSC increased FEV 1AUC 0–6h by 1.46±0.08 and 1.98±0.13 l-h at Day 1 and Week 8, respectively, in reversible patients, compared with 0.71±0.06 and 0.94±0.10 l-h in non-reversible patients ( p<0.001). With IB/ALB, increases were 1.46±0.08 and 1.19±0.11 l-h at Day 1 in reversible patients and Week 8, respectively, and 0.89±0.06 and 0.74±0.09 l-h ( p⩽0.041) in non-reversible patients. After 8 weeks, in both the reversible and non-reversible populations, the FEV 1 AUC 0–6h significantly increased with FSC treatment ( p⩽0.002) and significantly decreased with IB/ALB ( p⩽0.010). In both reversibility groups, improvement in Transition Dyspnea Index (TDI) scores, overall daytime diary symptom scores and nocturnal symptom measures were significantly greater with FSC treatment compared with IB/ALB ( p⩽0.044). Reversibility status was not predictive of the magnitude of reduction in symptom scores. We conclude that both reversible and non-reversible patients receive greater clinical benefit with FSC compared with IB/ALB and acute bronchodilator reversibility is not useful for differentiating patients based on symptomatic responses to FSC compared with IB/ALB.

Effects of 3-week Outpatient Pulmonary Rehabilitation on Exercise Capacity, Dyspnea, and Quality of Life in COPD

The effects of intensive 3-week outpatient pulmonary rehabilitation (PR) on exercise capacity, dyspnea, and health-related quality of life (HRQL) were investigated in patients with COPD. Two hundred ten patients with COPD (mean FEV(1) = 54%pred) underwent PR consisting of exercise training, patient and psychosocial education, breathing and relaxation therapy, nutrition counseling, and smoking cessation support. Before and after PR, exercise capacity was assessed with 6-min walking tests (6MWT) and constant cycle ergometer exercise (CEE). Dyspnea was measured after 6MWTs with a Borg scale and after PR with the Transition Dyspnoea Index (TDI). HRQL was examined with the Medical Outcomes Study Short Form 36 (SF-36). Results showed improvements in the 6MWT (+39 m, p < 0.001) and CEE (+241 W x min, p < 0.001) after PR, paralleled by decreased dyspnea during the 6MWT (-0.5, p < 0.001) and during activities (TDI score = 3.6). Increases in all SF-36 subscales reflected improved HRQL after PR (p < 0.001). No gender differences were found. Patients with milder versus more severe COPD improved similarly in most outcomes. Regression analyses revealed that TDI scores were the most important predictor of improvements in HRQL. The results suggest that intensive 3-week outpatient PR is associated with improvements in exercise capacity, dyspnea, and HRQL in male and female patients with COPD irrespective of COPD severity. Reduced dyspnea during activities contributed the most to improvements in HRQL.