Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Dec 2019
Meta Analysis Comparative StudyImpact of ICS/LABA and LABA/LAMA FDCs on functional and clinical outcomes in COPD: A network meta-analysis.
Inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) fixed-dose combinations (FDCs) and LABA/long-acting muscarinic antagonist (LAMA) FDCs are extensively used to treat chronic obstructive pulmonary disease (COPD). The aim of the present network meta-analysis was to assess the comparative efficacy of all the currently available dual therapies in patients with moderate-to-severe COPD. ⋯ The results of this meta-analysis show that LABA/LAMA combinations are consistently more effective than ICS/LABA FDCs for most of the evaluated outcomes. However, differences have also been observed between FDCs belonging to the same class. Across the investigated LABA/LAMA FDCs, glycopyrronium/indacaterol revealed a consistent and robust efficacy profile.
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Pulm Pharmacol Ther · Dec 2019
ReviewEmerging targets for cough therapies; NK1 receptor antagonists.
Cough is mediated by vagal afferent fibres innervating the larynx and proximal airways. Pre-clinical studies suggest that vagal C fibres produce Substance P, one of the tachykinin family of neuropeptides, which has been shown to enhance cough via the neurokinin-1 (NK-1) receptor and studies in animal models have also shown that NK-1 antagonists are effective at blocking induced cough. ⋯ More recently a small proof of concept study has suggest that aprepitant, an NK-1 antagonist licensed for the prevention of chemotherapy induced nausea and vomiting, might have beneficial effects on cough frequency in patients with lung cancer. In this review we investigate the current evidence for the anti-tussive effect of these therapies and the clinical trials in progress.
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Pulm Pharmacol Ther · Dec 2019
Meta Analysis Comparative StudyEfficacy and cardiovascular safety profile of dual bronchodilation therapy in chronic obstructive pulmonary disease: A bidimensional comparative analysis across fixed-dose combinations.
Despite several long-acting β2-adrenoceptor agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) are currently approved for the treatment of chronic obstructive pulmonary disease (COPD), there are limited findings concerning the direct comparison across the different LABA/LAMA FDCs. The aim of this study was to compare the efficacy/safety profile of approved LABA/LAMA FDCs in COPD. A network meta-analysis was performed by linking the efficacy (forced expiratory volume in 1 s, St' George Respiratory Questionnaire, transitional dyspnea index) and safety (cardiovascular serious adverse events) outcomes resulting from randomized controlled trials that directly compared LABA/LAMA FDCs with placebo and/or each other. ⋯ The IBiS score showed the following rank of efficacy/safety profile: tiotropium/olodaterol 5/5 μg (area 66.83%) » glycopyrronium/indacaterol 15.6/27.5 μg (area 40.43%) > umeclidinium/vilanterol 62.5/25 μg (area 30.48%) ≈ aclidinium/formoterol 400/12 μg (area 28.44%) > glycopyrronium/indacaterol 50/110 μg (area 19.95%) > glycopyrronium/formoterol 14.4/9.6 μg (area 11.50%). Each available LABA/LAMA FDC has a specific efficacy/safety profile that needs to be considered for personalized therapy in COPD. Head-to-head studies aimed to assess the impact of different LABA/LAMA FDCs on the risk of COPD exacerbation are needed to further improve the information provided by this quantitative synthesis.
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Pulm Pharmacol Ther · Oct 2019
ReviewRenin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation.
While effective treatments for acute respiratory distress syndrome (ARDS) are lacking, mechanical lung ventilation can sustain adequate gas exchange in critically ill patients with respiratory failure due to ARDS. However, as a result of the phenomenon of ventilator-induced lung injury (VILI), there is an increasing need to seek beneficial pharmacological therapies for ARDS. Recent studies have suggested the renin-angiotensin system (RAS), which consists of the ACE/Ang-II/AT1R axis and ACE2/Ang-(1-7)/MasR axis, plays a dual role in the pathogenesis of ARDS and VILI. This review highlights the deleterious action of ACE/Ang-II/AT1R axis and the beneficial role of ACE2/Ang-(1-7)/MasR axis, as well as AT2R, in VILI and ARDS, and also discusses the possibility of targeting RAS components with pharmacological interventions to improve outcomes in ARDS.
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Pulm Pharmacol Ther · Oct 2019
Effect of doxycyline in chronic obstructive pulmonary disease - An exploratory study.
Various mechanisms, including oxidative stress, inflammation, and protease-antiprotease imbalance are proposed for the progressive decline in lung function in chronic obstructive pulmonary disease (COPD). Doxycycline, a broad spectrum tetracycline antibiotic, is reported to have non-antimicrobial matrix metalloproteinases (MMP) inhibitory action in various inflammatory conditions. The effect of doxycycline in COPD is hereby assessed in the present randomized prospective study. ⋯ These data suggest that the improvement in lung function and quality of life in COPD patients may probably be attributed to the antioxidant, anti-inflammatory and anti-MMP activity of doxycycline. The potential therapeutic role of long-term doxycycline, in addition to its traditional antibiotic effect, definitely warrants further attention.