scholarly journals Effects of indacaterol on the LPS-evoked changes in fluid secretion rate and pH in swine tracheal membrane

2021 ◽  
Author(s):  
Hidemi Aritake ◽  
Tsutomu Tamada ◽  
Koji Murakami ◽  
Shunichi Gamo ◽  
Masayuki Nara ◽  
...  
Keyword(s):  
Airflow Obstruction ◽  
Fluid Secretion ◽  
Secretion Rate ◽  
Gland Secretion ◽  
Chronic Obstructive ◽  
Ph Indicator ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Ph Level ◽  
Long Acting

AbstractAn acquired dysregulation of airway secretion is likely involved in the pathophysiology of chronic bronchitis and chronic obstructive pulmonary disease (COPD). Nowadays, it is widely known that several kinds of long-acting bronchodilators reduce the frequency of COPD exacerbations. However, limited data are available concerning the complementary additive effects on airflow obstruction. Using an optical method and a selective pH indicator, we succeeded in evaluating the gland secretion rate and the pH in swine tracheal membrane. A physiologically relevant concentration of acetylcholine (ACh) 100 nM induced a gradual increase in the amount of gland secretion. Lipopolysaccharides (LPS) accelerated the ACh-induced secretory responses up to around threefold and lowered the pH level significantly. Long-acting β2-agonists (LABAs) including indacaterol (IND), formoterol, and salmeterol restored the LPS-induced changes in both the hypersecretion and acidification. The subsequent addition of the long-acting muscarine antagonist, glycopyrronium, further increased the pH values. Two different inhibitors for cystic fibrosis transmembrane conductance regulator (CFTR), NPPB and CFTRinh172, abolished the IND-mediated pH normalization in the presence of both ACh and ACh + LPS. Both immunofluorescence staining and western blotting analysis revealed that LPS downregulated the abundant expression of CFTR protein. However, IND did not restore the LPS-induced decrease in CFTR expression on Calu-3 cells. These findings suggest that the activation of cAMP-dependent HCO3− secretion through CFTR would be partly involved in the IND-mediated pH normalization in gland secretion and may be suitable for the maintenance of airway defense against exacerbating factors including LPS.

scholarly journals Prevention of COPD exacerbations: medications and other controversies

2015 ◽  
Vol 1 (1) ◽  
pp. 00011-2015 ◽  
Author(s):  
Jørgen Vestbo ◽  
Peter Lange
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Short Review ◽  
Chronic Obstructive ◽  
Evidence Based ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Different Types ◽  
Inflammatory Drugs ◽  
Long Acting

Exacerbations have significant impact on the morbidity and mortality of patients with chronic obstructive pulmonary disease. Most guidelines emphasise prevention of exacerbations by treatment with long-acting bronchodilators and/or anti-inflammatory drugs. Whereas most of this treatment is evidence-based, it is clear that patients differ regarding the nature of exacerbations and are likely to benefit differently from different types of treatment. In this short review, we wish to highlight this, suggest a first step in differentiating pharmacological exacerbation prevention and call for more studies in this area. Finally, we wish to highlight that there are perhaps easier ways of achieving similar success in exacerbation prevention using nonpharmacological tools.

scholarly journals LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis

2020 ◽  
Vol 14 ◽  
pp. 175346662093719
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chi-Hsien Huang ◽  
Yi-Ping Hsiang ◽  
Chau-Chyun Sheu ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Similar Efficacy ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
History Of ◽  
Long Acting

Background: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. Methods: We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. Results: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks). Conclusion: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.

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 Roflumilast does not decrease COPD exacerbations in adequately treated patients, but subgroup analysis allows for shared decision making

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Nathanael Sanchez
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Critical Appraisal ◽  
Respir Crit ◽  
Chronic Obstructive ◽  
Shared Decision ◽  
Inhaled Corticosteroid ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Long Acting ◽  
Beta2 Agonist

<p>A critical appraisal and clinical application of Martinez FJ, Rabe KF, Sethi S, et al. Effect of Roflumilast and Inhaled Corticosteroid/Long-Acting beta2-Agonist on Chronic Obstructive Pulmonary Disease Exacerbations (RE(2)SPOND). A Randomized Clinical Trial. <em>Am J Respir Crit Care Med</em>. Sep 1 2016;194(5):559-567. doi: <a href="https://doi.org/10.1164/rccm.201607-1349OC">10.1164/rccm.201607-1349OC</a>.</p>

scholarly journals Inaccurate diagnosis of COPD: the Welsh National COPD Audit

2018 ◽  
Vol 69 (678) ◽  
pp. e1-e7 ◽  
Author(s):  
Marie Fisk ◽  
Viktoria McMillan ◽  
James Brown ◽  
Juliana Holzhauer-Barrie ◽  
Muhammad S Khan ◽  
...  
Keyword(s):  
Primary Care ◽  
Correct Diagnosis ◽  
Airflow Obstruction ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Beta Agonists ◽  
Quality And Outcomes ◽  
Never Smokers ◽  
Long Acting ◽  
To Receive

BackgroundThe diagnosis of chronic obstructive pulmonary disease (COPD) is confirmed with spirometry demonstrating persistent airflow obstruction.AimTo evaluate the clinical characteristics and management of patients in primary care on COPD registers with spirometry incompatible with COPD.Design and settingA primary care audit of Welsh COPD Read-Coded patient data from the Quality and Outcomes Framework (QOF) COPD register in Wales.MethodPatients on the QOF COPD register with incompatible spirometry (post-bronchodilator forced expiratory lung volume in 1 second/forced vital capacity [FEV1/FVC] ratio ≥0.70) were compared with those with compatible spirometry (FEV1/FVC <0.70).ResultsThis audit included 63% of Welsh practices contributing 48 105 patients. Only 19% (n = 8957) of patients were post-bronchodilator FEV1/FVC Read-Coded and were included in this study. Of these, 75% (n = 6702) had compatible spirometry and 25% (n = 2255) did not. Patients with incompatible spirometry were more likely female (P = 0.009), never-smokers (P<0.001), had higher body mass index (P<0.001), and better mean FEV1 (P<0.001). Medical Research Council (MRC) breathlessness scores, exacerbation frequency, and asthma co-diagnosis were similar between groups. Patients in both groups were just as likely to receive inhaled corticosteroid (ICS) and long-acting beta-agonists (LABAs), but patients with incompatible spirometry were less likely to receive long-acting muscarinic antagonists (LAMAs) (P<0.001) or LABA/ICS (P = 0.002) combinations.ConclusionPatients on the COPD QOF register with spirometry incompatible with COPD are symptomatic and managed using significant resources. If quality of care and effective resource use are to be improved, focus must be given to correct diagnosis in this group.

scholarly journals Cardiovascular disease and COPD: dangerous liaisons?

2018 ◽  
Vol 27 (149) ◽  
pp. 180057 ◽  
Author(s):  
Klaus F. Rabe ◽  
John R. Hurst ◽  
Samy Suissa
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Recommended Treatment ◽  
Appropriate Treatment ◽  
Beneficial Impact ◽  
Β Blocker ◽  
Long Acting ◽  
Few Data

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently occur together and their coexistence is associated with worse outcomes than either condition alone. Pathophysiological links between COPD and CVD include lung hyperinflation, systemic inflammation and COPD exacerbations. COPD treatments may produce beneficial cardiovascular (CV) effects, such as long-acting bronchodilators, which are associated with improvements in arterial stiffness, pulmonary vasoconstriction, and cardiac function. However, data are limited regarding whether these translate into benefits in CV outcomes. Some studies have suggested that treatment with long-acting β2-agonists and long-acting muscarinic antagonists leads to an increase in the risk of CV events, particularly at treatment initiation, although the safety profile of these agents with prolonged use appears reassuring. Some CV medications may have a beneficial impact on COPD outcomes, but there have been concerns about β-blocker use leading to bronchospasm in COPD, which may result in patients not receiving guideline-recommended treatment. However, there are few data suggesting harm with these agents and patients should not be denied β-blockers if required. Clearer recommendations are necessary regarding the identification and management of comorbid CVD in patients with COPD in order to facilitate early intervention and appropriate treatment.

scholarly journals Prognostic and functional impact of perioperative LAMA/LABA inhaled therapy in patients with lung cancer and chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yoko Azuma ◽  
Atsushi Sano ◽  
Takashi Sakai ◽  
Satoshi Koezuka ◽  
Hajime Otsuka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Postoperative Complications ◽  
Lung Function ◽  
Retrospective Review ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Inhaled Therapy ◽  
Long Acting

Abstract Background Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting β2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. Methods Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. Results Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). Conclusions We believe this treatment combination is optimal for patients with lung cancer and COPD.

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