Impact of LABA/LAMA combination on exercise endurance and lung hyperinflation in COPD: A pair-wise and network meta-analysis

Calzetta, Luigino; Ora, Josuel; Cavalli, Francesco; Rogliani, Paola; O’Donnell, Denis E.; Cazzola, Mario

doi:10.1016/j.rmed.2017.06.020

Cited by 57 publications

(44 citation statements)

References 35 publications

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“…The superiority of dual combined long-acting beta-2 agonist and muscarinic antagonist (LABA/LAMA) bronchodilators relative to the individual mono-components is modest at best [90,91]. A systematic review of 99 RCTs indicates that while dual long-acting bronchodilators often reduce dyspnea, increase lung function (improved forced expiratory volume in 1 s, FEV 1 ), and improve quality of life compared to single long-acting bronchodilators or LABA/ inhaled corticosteroid (ICS) combinations [92], these results are not consistent and vary in magnitude.…”

Section: Reducing Lung Hyperinflationmentioning

confidence: 99%

Dyspnea in COPD: New Mechanistic Insights and Management Implications

et al. 2019

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Dyspnea is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD). To avoid exertional dyspnea, many patients adopt a sedentary lifestyle which predictably leads to extensive skeletal muscle deconditioning, social isolation, and its negative psychological sequalae. This ''dyspnea spiral'' is well documented and it is no surprise that alleviation of this distressing symptom has become a key objective highlighted across COPD guidelines. In reality, this important goal is often difficult to achieve, and successful symptom management awaits a Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.9970322.

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Section: Reducing Lung Hyperinflationmentioning

confidence: 99%

Dyspnea in COPD: New Mechanistic Insights and Management Implications

et al. 2019

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“…Studies have assessed improvements in transition dyspnea index (TDI), endurance capacity at a constant work rate, and inspiratory capacity (IC). A large pair‐wise network meta‐analysis of 8 published and unpublished studies including 6 randomized controlled trials in 1632 patients with moderate to severe COPD showed LABA/LAMA therapy to improve exercise endurance by 60 s in a constant work rate exercise protocol and improve IC by 229 ml compared with placebo (Calzetta et al, 2017). Bronchodilatation reduces the end expiratory lung volume (EELV), breathing starts at a lower point in the pressure‐volume curve, requiring less ventilatory drive and reduced intensity of dyspnea (O'Donnell, Revill, and Webb 2001; O'Donnell, Voduc, Fitzpatrick, & Webb, 2004; O'Donnell, Fluge, et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

The contribution of FEV ₁ and airflow limitation on the intensity of dyspnea and leg effort during exercise. Insights from a real‐world cohort

et al. 2020

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Rationale:The effort required to cycle and breathe intensify as power increases during incremental exercise. It is currently unclear how changes in FEV 1 in the presence or absence of airflow limitation) impacts the intensity of dyspnea and leg effort. This is clinically important as the improvement in FEV 1 is often the target for improving dyspnea. Objectives: To investigate the relationship between dyspnea (D), leg effort, power (P), and FEV 1 with and without airflow limitation using direct psychophysical scaling performed during incremental exercise testing to symptom limited capacity. Methods: Retrospective analysis of consecutive patients over the age of 35 referred for cardio-pulmonary exercise testing at McMaster University Medical Centre from 1988-2012.The modified Borg scale was used to measure dyspnea throughout incremental exercise testing. Measurements and results: 38,788 patients were included in the analysis [Mean Age 58.6 years (SD ±11.8), Males 61%, BMI 28.1 kg/m 2 (SD ±5.1), FEV 1 was 2.7 L (SD ±0.85), 95% predicted (SD ±20.4), FVC 3.4 L (SD ± 1.0), 94% predicted (SD ±17.0)], and 10.9% had airflow limitation (AL, FEV 1 /FVC < 70%). In a nonlinear regression analysis, the intensity of dyspnea increased in a positively accelerating manner with power and as the FEV 1 % predicted decreased: Dyspnea = 0.06 * Pow er 1.03 * FEV 1 %Pred −0.66 (r = .63). The intensity of leg effort increased with power and declining quadricep strength and FEV1% predicted: Leg Effort = 0.06 * Power 1 .22 * Quad −0.56 *FEV 1 %Pred −0.39 (r = .73). There was no independent effect of AL on dyspnea of leg effort. Conclusion: Power, quadriceps strength and FEV1 are the dominant factors contributing to dyspnea and leg effort, irrespective of the degree of airflow limitation. K E Y W O R D S cardio-pulmonary exercise testing, dyspnea, leg effort, physiology How to cite this article: Satia I, Farooqi MAM, Cusack R, et al. The contribution of FEV 1 and airflow limitation on the intensity of dyspnea and leg effort during exercise. Insights from a real-world cohort.

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“…Pharmacological trials where the statistical significance matches clinical provide the greatest probability that the investigated treatment will be effective in clinical practice . Interestingly, the concept of MCID has been only recently investigated in meta‐analyses in human respiratory medicine . The MID based on change in R L can be used in pharmacological trials to identify responder asthmatic horses to a bronchodilator agent and this approach will permit deep analyses of results beyond the usual comparison of groups .…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

Calzetta

Crupi

Roncada

et al. 2019

Equine Veterinary Journal

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Summary Background Airway obstruction is the main trait of severe equine asthma that affects respiratory function and elicits detrimental effects on clinical presentation. Only few and underpowered clinical studies have investigated the impact of improvement in lung function induced by bronchodilators on the clinical signs of asthma‐affected horses. Objectives To identify the minimal important difference (MID) in lung function elicited by bronchodilator leading to a meaningful improvement in clinical signs. Study design Pairwise meta‐analysis and meta‐regression analysis. Methods Literature searches were performed for studies that investigated the effect of bronchodilator therapy on lung function and clinical condition of asthmatic horses. The relationship between the change in lung function variables and clinical score was analysed via random‐effect meta‐regression. One‐point change of the Improved clinically Detectable Equine Asthma Scoring System (IDEASS) score was used to identify the MID. Results A significant (P<0.05) relationship was found between the changes in IDEASS score and maximum change in transpulmonary pressure (ΔPplmax) or pulmonary resistance (RL). Since only the model resulting for RL passed through the origin (Y‐intercept when X = 0: −0.31, 95% CI −0.75 to 0.14), this variable was used to identify the MID correlated with a meaningful improvement in clinical signs. The resulting MID value was a change in RL of 0.63 cm H2O/L/s (95% CI 0.33–0.94), representing the slope of meta‐regression model (high quality of evidence). Main limitations No long‐term studies investigated the effect of bronchodilator agents on both lung function and clinical signs in asthmatic horses. Conclusions In conclusion, bronchodilator pharmacotherapy in equine asthma elicits clinically meaningful effect when RL increases ≥1 cm H2O/L/s, a value indicating the MID. Assessing the MID based on change in RL may improve the quality of evidence and the scientific impact of future clinical trials as it extends beyond the simple, and limiting, evaluation of statistical significance.

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Impact of LABA/LAMA combination on exercise endurance and lung hyperinflation in COPD: A pair-wise and network meta-analysis

Cited by 57 publications

References 35 publications

Dyspnea in COPD: New Mechanistic Insights and Management Implications

Dyspnea in COPD: New Mechanistic Insights and Management Implications

The contribution of FEV ₁ and airflow limitation on the intensity of dyspnea and leg effort during exercise. Insights from a real‐world cohort

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

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Impact of LABA/LAMA combination on exercise endurance and lung hyperinflation in COPD: A pair-wise and network meta-analysis

Cited by 57 publications

References 35 publications

Dyspnea in COPD: New Mechanistic Insights and Management Implications

Dyspnea in COPD: New Mechanistic Insights and Management Implications

The contribution of FEV 1 and airflow limitation on the intensity of dyspnea and leg effort during exercise. Insights from a real‐world cohort

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

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The contribution of FEV ₁ and airflow limitation on the intensity of dyspnea and leg effort during exercise. Insights from a real‐world cohort