Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review

The efficacy and safety of two doses of aclidinium bromide were evaluated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).In this 24-week, double-blind trial, patients were randomised to twice-daily aclidinium (200 mg or 400 mg) or placebo. The primary efficacy end-point was change in trough forced expiratory volume in 1 s (FEV1) at week 24. Other end-points included peak FEV1, health status (St George's Respiratory Questionnaire; SGRQ) and dyspnoea (Transitional Dyspnoea Index; TDI).Overall, 828 patients were randomised. At week 24, significant improvements from baseline were observed with aclidinium 200 mg and 400 mg versus placebo for trough FEV1 (99 and 128 mL; both p,0.0001) and peak FEV1 (185 and 209 mL; both p,0.0001). Peak FEV1 improvements on day 1 were comparable with week 24. Aclidinium 200 mg and 400 mg produced significant improvements over placebo in baseline-adjusted mean SGRQ total score (-3.8 and -4.6 units; p,0.001 and p,0.0001) and TDI focal score (0.6 and 1.0 units; p,0.05 and p,0.001) at week 24. With both aclidinium doses, the incidence of anticholinergic adverse events was low, and similar to placebo.Twice-daily aclidinium significantly improved bronchodilation, health status and dyspnoea, and was well tolerated in patients with COPD.

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“…A similar lack of concordance between FEV1 and SGRQ has been observed in numerous other bronchodilator studies [12].…”

Section: Discussionsupporting

confidence: 84%

Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study

et al. 2012

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“…It is well established that there is, at best, a modest correlation between FEV 1 , the primary measure of disease severity in COPD, and clinical outcomes such as respiratory health-related quality of life and dyspnoea,19 20 and FEV 1 does not fully explain the morbidity associated with COPD. In this regard, our findings extend the results of other recent studies that demonstrated a relationship between CT metrics of COPD and clinically relevant outcomes.…”

Section: Discussionmentioning

confidence: 99%

Biomechanical CT metrics are associated with patient outcomes in COPD

Bodduluri

Bhatt

Hoffman

et al. 2017

Thorax

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Background Traditional metrics of lung disease such as those derived from spirometry and static single-volume CT images are used to explain respiratory morbidity in patients with chronic obstructive pulmonary disease (COPD), but are insufficient. We hypothesized that the mean Jacobian determinant, a measure of local lung expansion and contraction with respiration, would contribute independently to clinically relevant functional outcomes. Methods We applied image registration techniques to paired inspiratory-expiratory CT scans and derived the Jacobian determinant of the deformation field between the two lung volumes to map local volume change with respiration. We analyzed 490 participants with COPD with multivariable regression models to assess strengths of association between traditional CT metrics of disease and the Jacobian determinant with respiratory morbidity including dyspnea (mMRC), St Georges Respiratory Questionnaire (SGRQ) score, six-minute walk distance (6MWD), and the BODE index, as well as all-cause mortality. Results The Jacobian determinant was significantly associated with SGRQ (adjusted regression co-efficient β = −11.75,95%CI −21.6 to −1.7;p=0.020), and with 6MWD (β=321.15, 95%CI 134.1 to 508.1;p<0.001), independent of age, sex, race, body-mass-index, FEV1, smoking pack-years, CT emphysema, CT gas trapping, airway wall thickness, and CT scanner protocol. The mean Jacobian determinant was also independently associated with the BODE index (β= −0.41, 95%CI −0.80 to −0.02; p = 0.039), and mortality on follow-up (adjusted hazards ratio = 4.26, 95%CI = 0.93 to 19.23; p = 0.064). Conclusion Biomechanical metrics representing local lung expansion and contraction improve prediction of respiratory morbidity and mortality and offer additional prognostic information beyond traditional measures of lung function and static single-volume CT metrics.

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“…It may be that azithromycin can improve lung function in patients with OB/BOS, but a larger number of patients are needed to see this effect. However, if this is the case, and larger studies are able to determine a statistically significant benefit of azithromycin in OB/BOS, it will be important to also consider whether such a difference is clinically meaningful 33 . As the timing of the initiation of azithromycin in the course of OB naturally varied in these studies, it is also unknown whether earlier therapy might prevent progression.…”

Section: Discussionmentioning

confidence: 99%

Azithromycin for the Treatment of Obliterative Bronchiolitis after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Yadav

Peters

Keogh

et al. 2016

Biology of Blood and Marrow Transplantation

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Obliterative bronchiolitis (OB) is a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Our objective was to perform a systematic review and meta-analysis of the impact of azithromycin on change in forced expiratory volume in 1 second (FEV1). We searched MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL and Scopus databases. We included studies that compared azithromycin to placebo or no intervention in the treatment of OB or BOS in patients who had undergone allogeneic HSCT. 91 unique publications were identified. 4 studies met inclusion criteria, with a total of 90 patients. Changes in FEV1 were measured between 12 weeks and 24 weeks after initiation of treatment. The meta-analysis demonstrated a mean increase in FEV1 of 30 ml (95% Confidence Interval: -260 to +330 ml, p = 0.82) following initiation of azithromycin. One patient death was reported, but not attributed to azithromycin therapy. In conclusion, current evidence can neither support nor refute the use of azithromycin in the treatment of patients who develop OB/BOS following HSCT. Further studies are needed to determine whether azithromycin is beneficial for the treatment of OB/BOS in this setting.

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Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review

Cited by 121 publications

References 43 publications

Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study

Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study

Biomechanical CT metrics are associated with patient outcomes in COPD

Azithromycin for the Treatment of Obliterative Bronchiolitis after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

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