52
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Relationship between FEV 1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV 1 and changes in health status with bronchodilator therapy.

          Methods

          Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV 1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV 1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score.

          Results

          Thirty-six studies (≥3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV 1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV 1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV 1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV 1. The association between change in FEV 1 and other patient-reported outcomes was generally weak.

          Conclusions

          Our analyses indicate, at a study level, that improvement in mean trough FEV 1 is associated with proportional improvements in health status.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: not found

          A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease.

          Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            St. George's Respiratory Questionnaire: MCID.

            The SGRQ is a disease-specific measure of health status for use in COPD. A number of methods have been used for estimating its minimum clinically important difference (MCID). These include both expert and patient preference-based estimates. Anchor-based methods have also been used. The calculated MCID from those studies was consistently around 4 units, regardless of assessment method. By contrast, the MCID calculated using distribution-based methods varied across studies and permitted no consistent estimate. All measurements of clinical significance contain sample and measurement error. They also require value judgements, if not about the calculation of the MCID itself then about the anchors used to estimate it. Under these circumstances, greater weight should be placed upon the overall body of evidence for an MCID, rather than one single method. For that reason, estimates of MCID should be used as indicative values. Methods of analysing clinical trial results should reflect this, and use appropriate statistical tests for comparison with the MCID. Treatments for COPD that produced an improvement in SGRQ of the order of 4 units in clinical trials have subsequently found wide acceptance once in clinical practice, so it seems reasonable to expect any new treatment proposed for COPD to produce an advantage over placebo that is not significantly inferior to a 4-unit difference.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial.

              Treatment of moderate or severe chronic obstructive pulmonary disease (COPD) with combinations of inhaled corticosteroids, long-acting beta-agonists, and long-acting anticholinergic bronchodilators is common but unstudied. To determine whether combining tiotropium with salmeterol or fluticasone-salmeterol improves clinical outcomes in adults with moderate to severe COPD compared with tiotropium alone. Randomized, double-blind, placebo-controlled trial conducted from October 2003 to January 2006. 27 academic and community medical centers in Canada. 449 patients with moderate or severe COPD. 1 year of treatment with tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus fluticasone-salmeterol. The primary end point was the proportion of patients who experienced an exacerbation of COPD that required treatment with systemic steroids or antibiotics. The proportion of patients in the tiotropium plus placebo group who experienced an exacerbation (62.8%) did not differ from that in the tiotropium plus salmeterol group (64.8%; difference, -2.0 percentage points [95% CI, -12.8 to 8.8 percentage points]) or in the tiotropium plus fluticasone-salmeterol group (60.0%; difference, 2.8 percentage points [CI, -8.2 to 13.8 percentage points]). In sensitivity analyses, the point estimates and 95% confidence bounds shifted in the direction favoring tiotropium plus salmeterol and tiotropium plus fluticasone-salmeterol. Tiotropium plus fluticasone-salmeterol improved lung function (P = 0.049) and disease-specific quality of life (P = 0.01) and reduced the number of hospitalizations for COPD exacerbation (incidence rate ratio, 0.53 [CI, 0.33 to 0.86]) and all-cause hospitalizations (incidence rate ratio, 0.67 [CI, 0.45 to 0.99]) compared with tiotropium plus placebo. In contrast, tiotropium plus salmeterol did not statistically improve lung function or hospitalization rates compared with tiotropium plus placebo. More than 40% of patients who received tiotropium plus placebo and tiotropium plus salmeterol discontinued therapy prematurely, and many crossed over to treatment with open-label inhaled steroids or long-acting beta-agonists. Addition of fluticasone-salmeterol to tiotropium therapy did not statistically influence rates of COPD exacerbation but did improve lung function, quality of life, and hospitalization rates in patients with moderate to severe COPD. International Standard Randomised Controlled Trial registration number: ISRCTN29870041.
                Bookmark

                Author and article information

                Journal
                Respir Res
                Respiratory Research
                BioMed Central
                1465-9921
                1465-993X
                2011
                8 April 2011
                : 12
                : 1
                : 40
                Affiliations
                [1 ]Kleijnen Systematic Reviews Ltd., York, UK
                [2 ]Respiratory Epidemiology and Clinical Research Unit, McGill University, Montreal, Canada
                [3 ]St George's University Medical School, University of London, UK
                [4 ]Novartis Pharma AG, Basel, Switzerland
                Article
                1465-9921-12-40
                10.1186/1465-9921-12-40
                3090353
                21477298
                44daf745-6da5-4a86-acda-36a32daf2926
                Copyright ©2011 Westwood et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 January 2011
                : 8 April 2011
                Categories
                Review

                Respiratory medicine
                Respiratory medicine

                Comments

                Comment on this article