scholarly journals The TRIFLOW study: a randomised, cross-over study evaluating the effects of extrafine beclometasone/formoterol/glycopyrronium on gas trapping in COPD

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
James Dean ◽  
Catalina Panainte ◽  
Naimat Khan ◽  
Dave Singh
Keyword(s):  
Lung Function ◽  
Triple Therapy ◽  
Small Airway ◽  
Mean Difference ◽  
Open Label ◽  
Post Dose ◽  
Airway Function ◽  
Copd Patients ◽  
Gas Trapping ◽  
Long Acting

Abstract Background The effects of triple therapy on gas trapping in COPD are not fully understood. We evaluated the effects of the long acting bronchodilator components of the extrafine single inhaler triple therapy beclometasone dipropionate/formoterol/glycopyrronium (BDP/F/G) pMDI on gas trapping. Methods This open-label, randomised, single centre, 2-way cross-over study recruited 23 COPD patients taking inhaled corticosteroid combination treatments and with residual volume (RV) > 120% predicted at screening. Inhaled BDP was taken during run-in and washout periods. Baseline lung function (spirometry, lung volumes, oscillometry) was measured over 12 h prior to randomisation to BDP/F/G or BDP/F for 5 days followed by washout and crossover. Lung function was measured prior to dosing on day 1 and for 12 h post-dose on day 5. Results Co-primary endpoint analysis: BDP/F/G had a greater effect than BDP/F on FEV1 area under the curve over 12 h (AUC0–12) (mean difference 104 mls, p = 0.0071) and RV AUC0–12 (mean difference − 163 mls, p = 0.0028). Oscillometry measurements showed a greater effect of BDP/F/G on the difference between resistance at 5 and 20 Hz (R5–R20) AUC0–12, which measures small airway resistance (mean difference − 0.045 kPa/L/s, p = 0.0002). Comparison of BDP/F with the baseline measurements (BDP alone) showed that F increased FEV1 AUC0–12 (mean difference 227 mls) and improved RV AUC0–12 (mean difference − 558 mls) and R5–R20 AUC0–12 (mean difference − 0.117 kPa/L/s), all p < 0.0001. Conclusions In COPD patients with hyperinflation, the G and F components of extrafine BDP/F/G improved FEV1, RV and small airway function. These long acting bronchodilators target small airway function, thereby improving gas trapping and airflow. Trial registration The study was retrospectively registered at ClinicalTrials.gov on 15th February 2019 (No.: NCT03842904, https://clinicaltrials.gov/ct2/show/NCT03842904).

scholarly journals GLIMPSE STUDY: IMPACT OF TRIPLE THERAPY ON LUNG FUNCTION, HEALTH STATUS, AND MORTALITY RISK IN PATIENTS WITH ADVANCED CHRONIC OBSTRUCTIVE PULMONARY DISEASE

2021 ◽  
pp. 190-195
Author(s):  
SALVA FATIMA HEBA ◽  
SYED AAMIR ALI ◽  
MOHAMMED ALEEMUDDIN NAVEED ◽  
SALWA MEHRIN ◽  
MAARIA GULNAAZ ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Health Status ◽  
Lung Function ◽  
Triple Therapy ◽  
Pulmonary Disease ◽  
Mortality Risk ◽  
Mean Difference ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Objectives: The objectives of the study were to estimate the relative impact of triple therapy on lung function, health status, and mortality risk compared with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) therapy in symptomatic chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations in an Indian clinical population. Methodology: The GLIMPSE (Lung Function, Health Status, and Mortality Risk Assessment in COPD using Triple Therapy) was as a prospective, parallel design, single-center observational study comparing 24 weeks of triple therapy (twice-daily combination of budesonide [BUD]-formoterol [FOR] [100/6 μg] and once-daily tiotropium [TIO] [9 μg]) with ICS/LABA (twice daily BUD-FOR [100/6 μg]). The primary outcome was the mean change in forced expiratory volume in the 1st s (FEV1%) predicted and COPD assessment test total score from baseline at week 24. Secondary outcomes were variation in dyspnea grade and BODE total score from baseline. Results: At week 24 in triple therapy (n=70) and ICS/LABA therapy (n=70), mean difference from baseline in FEV1% predicted were 5.40 (95% confidence interval [CI]: 1.29–9.50) and 1.90 (95% CI: –1.87–5.68) respectively, and mean difference in CAT total score from baseline was –5.10 units (95% CI: –3.49–−6.71) and –1.80 units (95% CI: –0.052–−3.548), respectively. In addition, there was a statistically significant reduction in dyspnea grading and BODE score with comparable adverse events in both groups. Conclusion: Overall, the results favored triple therapy over dual therapy in advanced symptomatic COPD patients.

scholarly journals Costs, exacerbations and pneumonia after initiating combination tiotropium olodaterol versus triple therapy for chronic obstructive pulmonary disease

2019 ◽  
Vol 8 (15) ◽  
pp. 1299-1316 ◽  
Author(s):  
Swetha R Palli ◽  
Ami R Buikema ◽  
Mary DuCharme ◽  
Monica Frazer ◽  
Shuchita Kaila ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Triple Therapy ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Inverse Probability ◽  
Copd Patients ◽  
Baseline Characteristics ◽  
Long Acting ◽  
Medicare Database

Aim: To compare health plan-paid costs, exacerbations and pneumonia outcomes for patients with chronic obstructive pulmonary disease (COPD) initiating combination tiotropium olodaterol (TIO + OLO) versus triple therapy (TT: long-acting muscarinic antagonist + long-acting β2 agonists + inhaled corticosteroid). Patients & methods: COPD patients initiating TIO + OLO or TT between 1 January 2014 and 30 June 2016 were identified from a managed care Medicare database and balanced for baseline characteristics using inverse probability of treatment weighting before assessment of outcomes. Results: Annual COPD-related and all-cause costs were US$4118 (35%) and US$5384 (23%) lower for TIO + OLO versus TT (both p ≤ 0.001). TIO + OLO patients had nearly half the severe exacerbations (8.3 vs 15.5%; p = 0.014) and pneumonia was also less common (18.9 vs 30.9%; p < 0.001). Conclusion: TIO + OLO was associated with improved economic and COPD health outcomes versus TT.

scholarly journals Increased myofibroblasts in the small airways and relation to remodelling and functional changes in smokers and COPD patients: potential role of epithelial-mesenchymal transition (EMT)

2021 ◽  
pp. 00876-2020
Author(s):  
Mathew Suji Eapen ◽  
Wenying Lu ◽  
Tillie L. Hackett ◽  
Gurpreet Kaur Singhera ◽  
Malik Q. Mahmood ◽  
...  
Keyword(s):  
Lung Function ◽  
Epithelial Mesenchymal Transition ◽  
Small Airway ◽  
Normal Lung ◽  
Small Airways ◽  
Mesenchymal Transition ◽  
Functional Changes ◽  
Highly Active ◽  
Copd Patients ◽  
Normal Lung Function

IntroductionPrevious reports showed epithelial mesenchymal transition (EMT) as an active process that contributes to small airway (SA) fibrotic pathology. Myofibroblasts are highly active pro-fibrotic cells that secrete excessive and altered extracellular matrix (ECM). Here we relate SA myofibroblast presence with airway remodelling, physiology and EMT activity in smokers and COPD patients.MethodsLung resections from non-smoker controls (NC), normal lung function smokers (NLFS), COPD current (CS) and ex-smokers (ES) were stained with anti-human αSMA, collagen 1, and fibronectin. αSMA+ive cells were computed in reticular basement membrane (Rbm), lamina propria (LP), and adventitia and presented per mm of Rbm and mm2 of LP. Collagen-1 and fibronectin are presented as a percentage change from normal. All analysis including airway thickness were measured using Image-pro-plus 7.0.ResultsWe found an increase in sub-epithelial LP (especially) and adventitia thickness in all pathological groups compared to NC. Increases in αSMA+ive myofibroblasts were observed in sub-epithelial Rbm, LP, and adventitia in both the smoker and COPD groups compared to NCs. Further, the increase in the myofibroblast population in the LP was strongly associated with decrease in lung function, LP thickening, increase in ECM protein deposition, and finally EMT activity in epithelial cells.ConclusionsThis is the first systematic characterisation of small airway myofibroblasts in COPD based on their localisation, with statistically significant correlations between them and other pan-airway structural, lung function, and ECM protein changes. Finally, we suggest that EMT may be involved in such changes.

scholarly journals Single inhaler triple therapy in COPD – all that glitters is not gold

2021 ◽  
Vol 91 (2) ◽  
Author(s):  
Kartik Deshmukh ◽  
Arjun Khanna
Keyword(s):  
Lung Function ◽  
Triple Therapy ◽  
Inhaled Corticosteroid ◽  
Muscarinic Antagonist ◽  
Exacerbation Frequency ◽  
Long Acting ◽  
Beta2 Agonist

Dear Editor, The recent studies on combination triple therapy of inhaled corticosteroid, long acting beta2 agonist and long-acting muscarinic antagonist (ICS-LABA-LAMA) in COPD have consistently demonstrated an improvement in exacerbation frequency and/or improvement of lung function...

Real-Life Clinical and Functional Effects of Fluticasone Furoate/Umeclidinium/Vilanterol-Combined Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease

Respiration ◽  
2020 ◽  
pp. 1-8
Author(s):  
Corrado Pelaia ◽  
Giada Procopio ◽  
Maria Rosaria Deodato ◽  
Olivia Florio ◽  
Angelantonio Maglio ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Triple Therapy ◽  
Real Life ◽  
Chronic Obstructive ◽  
Fluticasone Furoate ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
Inhaled Therapy ◽  
Long Acting

<b><i>Background:</i></b> Triple therapy consisting of a drug association including an inhaled corticosteroid, a long-acting muscarinic receptor antagonist and a long-acting β<sub>2</sub>-adrenergic agonist, delivered via a single device, can be a valuable treatment for chronic obstructive pulmonary disease (COPD) patients experiencing frequent disease exacerbations. <b><i>Objectives:</i></b> The aim of this real-life, single-center, observational study was to evaluate, in 44 COPD patients with recurrent exacerbations, the effects of the triple inhaled therapy combining fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI). <b><i>Methods:</i></b> Within such a therapeutic context, several clinical and lung functional parameters were considered at baseline and after 24 weeks of treatment with combined inhaled triple therapy. <b><i>Results:</i></b> With respect to baseline, after 24 weeks of treatment with FF/UMEC/VI, significant changes were recorded with regard to Modified British Medical Research Council (<i>p</i> &#x3c; 0.0001) and COPD Assessment Test (<i>p</i> &#x3c; 0.0001) scores, COPD exacerbations (<i>p</i> &#x3c; 0.001), forced expiratory volume in the first second (<i>p</i> &#x3c; 0.001), residual volume (<i>p</i> &#x3c; 0.01), forced mid-expiratory flow between 25 and 75% of FVC (<i>p</i> &#x3c; 0.0001), inspiratory capacity (<i>p</i> &#x3c; 0.01), forced vital capacity (<i>p</i> &#x3c; 0.05), and peak expiratory flow (<i>p</i> &#x3c; 0.0001). Moreover, in a subgroup of 28 patients, a significant increase of diffusion lung capacity (<i>p</i> &#x3c; 0.01) was also detected. <b><i>Conclusions:</i></b> In conclusion, our real-life results suggest that triple inhaled therapy with FF/UMEC/VI, when given to COPD patients with frequent exacerbations, is able to positively impact on dyspnea and global health status as well as to significantly decrease COPD exacerbations and improve airflow limitation and lung hyperinflation.

scholarly journals Nasal High Flow at 25 L/min or Expiratory Resistive Load Do Not Improve Regional Lung Function in Patients With COPD: A Functional CT Imaging Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Julien G. Cohen ◽  
Ludovic Broche ◽  
Mohammed Machichi ◽  
Gilbert R. Ferretti ◽  
Renaud Tamisier ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Ventilation ◽  
Ct Imaging ◽  
High Flow ◽  
Flow Rates ◽  
Copd Patients ◽  
Regional Lung Function ◽  
Gas Trapping ◽  
Regional Lung ◽  
Regional Lung Ventilation

BackgroundNasal high flow (NHF) is a non-invasive breathing therapy that is based on the delivery via a large-caliber nasal cannula of heated and humidified air at flow rates that exceed peak inspiratory flow. It is thought that positive airway pressure generated by NHF can help reduce gas trapping and improve regional lung ventilation. There are no data to confirm this hypothesis at flow rates applicable in stable chronic obstructive pulmonary disease (COPD) patients.MethodsIn this study, we used non-rigid registration of computed tomography (CT) images acquired at maximal expiration and inspiration to compute regional lung attenuation changes (ΔHU), and lung displacement (LD), indices of regional lung ventilation. Parametric response maps (Galban et al., 2012) were also computed in each experimental condition. Eight COPD patients were assessed at baseline (BL) and after 5 min of NHF and expiratory resistive loading (ERL).ResultsΔHU was: BL (median, IQR): 85 (67.2, 102.8); NHF: 90.7 (57.4, 97.6); ERL: 74.6 (46.4, 89.6) HU (p = 0.531); and LD: 27.8 (22.3, 39.3); 17.6 (15.4, 27.9); and 20.4 (16.6, 23.6) mm (p = 0.120) in the 3 conditions, respectively. No significant difference in trapping was observed. Respiratory rate significantly decreased with both treatments [BL: 17.3 (16.4, 18.9); NHF: 13.7; ERL: 11.4 (9.6, 13.2) bpm; and p &lt; 0.001].ConclusionNeither NHF at 25 L/min nor ERL significantly improved the regional lung ventilation of stable COPD patients with gas trapping, based on functional lung CT imaging. Further study including more subjects is needed to assess the potential effect of NHF on regional lung function at higher flow rates.Clinical Trial Registrationwww.clinicaltrials.gov/under, identifier NCT03821311.

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