Indacaterol/Glycopyrronium Combination for COPD

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LABA/LAMA combination in COPD: a meta-analysis on the duration of treatment

When there are no randomised clinical trials directly comparing all relevant treatment options, an indirect treatment comparison via meta-analysis of the available clinical evidence is an acceptable alternative. However, meta-analyses may be very misleading if not adequately performed. Here, we propose and validate a simple and effective approach to meta-analysis for exploring the effectiveness of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations in chronic obstructive pulmonary disease.14 articles with 20 329 patients (combinations n=9292; monocomponents n=11 037) were included in this study. LABA/LAMA combinations were always more effective than the monocomponents in terms of the improvement in trough forced expiratory volume in 1 s, transition dyspnoea index and St George's Respiratory Questionnaire scores after 3, 6 and 12 months of treatment. No significant publication bias was identified. Significant discrepancies with previous network meta-analyses have been found, with overall differences ranging from 26.7% to 43.3%.Results from previous network meta-analyses were misleading because no adequate attention was given to formulating the review question, specifying eligibility criteria, correctly identifying studies, collecting appropriate information and deciding what it would be pharmacologically relevant to analyse. The real gradient of effectiveness of LABA/LAMA fixed-dose combinations remains an unmet medical need; however, it can be investigated indirectly using a high-quality meta-analytic approach

Hyperglycaemia and Chronic Obstructive Pulmonary Disease

: Chronic obstructive pulmonary disease (COPD) may coexist with type 2 diabetes mellitus (T2DM). Patients with COPD have an increased risk of developing T2DM compared with a control but, on the other side, hyperglycaemia and DM have been associated with reduced predicted levels of lung function. The mechanistic relationships between these two diseases are complicated, multifaceted, and little understood, yet they can impact treatment strategy. The potential risks and benefits for patients with T2DM treated with pulmonary drugs and the potential pulmonary risks and benefits for patients with COPD when taking antidiabetic drugs should always be considered. The interaction between the presence and/or treatment of COPD, risk of infection, presence and/or treatment of T2DM and risk of acute exacerbations of COPD (AECOPDs) can be represented as a vicious circle; however, several strategies may help to break this circle. The most effective approach to simultaneously treating T2DM and COPD is to interfere with the shared inflammatory substrate, thus targeting both lung inflammation (COPD) and vascular inflammation (DM). In any case, it is always crucial to establish glycaemic management since the reduction in lung function found in people with diabetes might decrease the threshold for clinical manifestations of COPD. In this article, we examine possible connections between COPD and T2DM as well as pharmacological strategies that could focus on these connections

analysis of exhaled breath fingerprints and volatile organic compounds in copd

Exhaled air contains many volatile organic compounds (VOCs) produced during human metabolic processes, in both healthy and pathological conditions. Analysis of breath allows studying the modifications of the profile of the exhaled VOCs due to different disease states, including chronic obstructive pulmonary disease (COPD). The early diagnosis of COPD is complicated and the identification of specific metabolic profiles of exhaled air may provide useful indication to better identify the disease. The aim of our study was to characterize the specific exhaled VOCs by means of the electronic nose and by solid phase micro-extraction associated to gas chromatography–mass spectrometry (SPME GC-MS). Exhaled air was collected and measured in 34 subjects, 7 healthy and 27 former smokers affected by COPD (GOLD 1–4). The signals of the electronic nose sensors were higher in COPD patients with respect to controls, and allowed to accurately classify the studied subjects in healthy or COPD. GC-MS analysis identified 37 VOCs, nine of which were significantly correlated with COPD. In particular the concentration of two of these were positively correlated whereas seven were negatively correlated with COPD. The partial least squares discriminant analysis (PLS-DA) carried out with these nine VOCs produced a significant predictive model of disease. This study shows that COPD patients exhibit qualitative and quantitative differences in the chemical compositions of exhale. These differences are detectable both by the GC-MS and the six-sensor e-nose. The use of electronic nose may represent a suitable, non-invasive diagnostic tool for characterization of COPD

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

Differential pharmacology and clinical utility of long-acting bronchodilators in COPD – Focus on olodaterol

Olodaterol (BI 1744 CL) is a novel, once-daily long-acting β2-agonist (LABA) designed with the aim of improving β2-adrenoreceptor selectivity and intrinsic activity. Phase III pivotal trials have documented that olodaterol Respimat Soft Mist inhaler 5 μg induces fast onset of bronchodilation, comparable with formoterol at day 1. Moreover, significant lung function improvements have been documented up to 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Olodaterol was generally well tolerated and had an acceptable cardiovascular and respiratory adverse event profile. Regrettably, the clinical development of olodaterol is however still too partial to draw any firm conclusions on the positioning of this ultra-LABA as monotherapy in the management of COPD. Waiting for further data on the impact of olodaterol on different patient-reported outcomes, which however are widely available for indacaterol, and mainly for a head-to-head comparison between these two ultra-LABAs and between olodaterol long-acting antimuscarinic antagonists other than tiotropium, we believe it is correct to follow the clinical indications of indacaterol also for olodaterol. In any case, the parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The results from the ongoing large TOviTO Phase III trial program have documented the efficacy and safety of olodaterol/tiotropium fixed-dose combination as maintenance therapy in patients with moderate to very severe COPD. In particular, olodaterol/tiotropium fixed-dose combination provides a convincing alternative for patients remaining symptomatic with olodaterol monotherapy

Autonomic system modification in zen practitioners

BACKGROUND: Meditation in its various forms is a traditional exercise with a potential benefit on well-being and health. On a psychosomatic level these exercises seem to improve the salutogenetic potential in man.Especially the cardiorespiratory interaction seems to play an important role since most meditation techniques make use of special low frequency breathing patterns regardless of whether they result from a deliberate guidance of breathing or other mechanisms, for example, the recitation of specific verse. During the different exercises of Zen meditation the depth and the duration of each respiratory cycle is determined only by the process of breathing. Respiratory manoeuvres during Zazen meditation may produce HR variability changes similar to those produces during biofeedback.Recognition that the respiratory sinus arrhythmia (RSA) was mediated by efferent vagal activity acting on the sinus node led investigators to attempt to quantify the fluctuations in R-R intervals that were related to breathing. MATERIALS AND METHODS: Nine Zen practitioners with five years of experience took part in the study. Autonomic nervous system function was evaluated by heart rate variability (HRV) analysis during 24-hours ECG recording during zen meditation and at rest. RESULTS: The data of this small observational study confirm that ZaZen breathing falls within the range of low frequency HR spectral bands. Our data suggest that the modification of HR spectral power remained also in normal day when the subject have a normal breathing. CONCLUSION: We suggest that the changes in the breathing rate might modify the chemoreflex and the continuous practice in slow breathing can reduce chemoreflex. This change in the automonic control of respiration can be permanent with a resetting of endogenous circulatory rhythms

Differential pharmacology and clinical utility of long-acting bronchodilators in COPD – focus on olodaterol

Olodaterol (BI 1744 CL) is a novel, once-daily long-acting β2-agonist (LABA) designed with the aim of improving β2-adrenoreceptor selectivity and intrinsic activity. Phase III pivotal trials have documented that olodaterol Respimat Soft Mist inhaler 5 μg induces fast onset of bronchodilation, comparable with formoterol at day 1. Moreover, significant lung function improvements have been documented up to 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Olodaterol was generally well tolerated and had an acceptable cardiovascular and respiratory adverse event profile. Regrettably, the clinical development of olodaterol is however still too partial to draw any firm conclusions on the positioning of this ultra-LABA as monotherapy in the management of COPD. Waiting for further data on the impact of olodaterol on different patient-reported outcomes, which however are widely available for indacaterol, and mainly for a head-to-head comparison between these two ultra-LABAs and between olodaterol long-acting antimuscarinic antagonists other than tiotropium, we believe it is correct to follow the clinical indications of indacaterol also for olodaterol. In any case, the parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The results from the ongoing large TOviTO Phase III trial program have documented the efficacy and safety of olodaterol/tiotropium fixed-dose combination as maintenance therapy in patients with moderate to very severe COPD. In particular, olodaterol/tiotropium fixed-dose combination provides a convincing alternative for patients remaining symptomatic with olodaterol monotherapy

Current pharmacotherapeutic options for pediatric lower respiratory tract infections with a focus on antimicrobial agents

Introduction: Antibiotics are frequently prescribed to children in the community and in nosocomial settings, mainly because of lower respiratory tract infections(LRTIs), which include influenza, bronchitis, bronchiolitis, pneumonia, and tuberculosis, in addition to bronchiectasis and cystic fibrosis lung disease. It is important to note, however, that more than 50% of these prescriptions are unnecessary or inappropriate. Areas covered: The current choice of antimicrobial therapy for etiological agents of LRTIs is examined and discussed considering each type of LRTI. Expert opinion: There is a clear need for the appropriate utilization of antibiotics in children. Therefore, accurate drug selection and choice of best dosage and duration of the antibacterial treatment are important to optimize the treatment of LRTIs. It’s fundamental to bear in mind that children differ from adults in how LRTIs manifest and evolve not only because of the diversity in the immunological profiles but also the fundamental age-related differences in absorption, distribution, metabolism, and elimination of drugs. Since comprehensive antibiotic guideline recommendations for the treatment of pediatric LRTIs are generally lacking, there is an undeniable need for the introduction of pediatric antimicrobial stewardship programmes in both community and hospital settings