Pharmacological management of COVID-19 patients with ARDS (CARDS): A narrative review

Coronavirus disease 2019 (COVID-19) is highly infectious. It has been highlighted that if not expertly and individually managed with consideration of the vasocentric features, a COVID-19 patient with an acute respiratory distress syndrome (CARDS) may eventually develop multiorgan failure. Unfortunately, there is still no definite drug for CARDS that is capable of reducing either short-term or long-term mortality and no specific treatments for COVID-19 exist right now. In this narrative review, based on a selective literature search in EMBASE, MEDLINE, Scopus, The Cochrane Library, Web of Science, and Google Scholar and ClinicalTrials.gov, we have examined the emerging evidence on the possible treatment of CARDS. Although numerous pharmacologic therapies to improve clinical outcomes in CARDS have been studied also in clinical trials, none have shown efficacy and there is great uncertainty about their effectiveness. There is still no recommendation for the therapeutic use of any specific agent to treat CARDS because no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale trials. However, there exist a number of drugs that may be useful at least in some patients. The real challenge now is to link the right patient to the right treatment

Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: a pilot study.

BACKGROUND: The synergistic interactions between pharmacotherapy and pulmonary rehabilitation has been provided, but it remains to be established whether this may also apply to more severe patients. OBJECTIVES: We have examined whether tiotropium enhances the effects of exercise training in patients with advanced COPD (FEV(1)</=60% predicted, hypoxemia at rest corrected with oxygen supplementation, and limitations of physical activity). METHODS: We enrolled 22 patients that were randomised to tiotropium 18mug or placebo inhalation capsules taken once daily. Both groups (11 patients in each group) underwent an in patient pulmonary rehabilitation program and were under regular treatment with salmeterol/fluticasone twice daily. Each rehabilitation session was held 5 days per week (3h/day) for a total of 4 weeks. RESULTS: Compared to placebo, tiotropium had larger impact on pulmonary function (FEV(1)+0.164L, FVC +0.112L, RV -0.544L after tiotropium, FEV(1)+0.084L, FVC -0.039L, RV -0.036L after placebo). The addition of tiotropium allowed a longer distance walked in 6min (82.3m vs. 67.7m after placebo) and reduced dyspnoea (Borg score) (-0.4 vs. +0.18 after placebo) when compared with baseline (pre pulmonary rehabilitation program). The changes in SGRQ from baseline to the end of treatment were: total score -28.3U, activity -27.8U, impact -14.5U, and symptoms -33.4U in the placebo group; and total score -19.1U, activity -18.9U, impact -16.4U, and symptoms -33.8U in the tiotropium group. CONCLUSIONS: Our study clearly indicates that there is an advantage in combining pulmonary rehabilitation with an aggressive drug therapy in more severe patient

Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: a pilot study.

BACKGROUND: The synergistic interactions between pharmacotherapy and pulmonary rehabilitation has been provided, but it remains to be established whether this may also apply to more severe patients. OBJECTIVES: We have examined whether tiotropium enhances the effects of exercise training in patients with advanced COPD (FEV(1)</=60% predicted, hypoxemia at rest corrected with oxygen supplementation, and limitations of physical activity). METHODS: We enrolled 22 patients that were randomised to tiotropium 18mug or placebo inhalation capsules taken once daily. Both groups (11 patients in each group) underwent an in patient pulmonary rehabilitation program and were under regular treatment with salmeterol/fluticasone twice daily. Each rehabilitation session was held 5 days per week (3h/day) for a total of 4 weeks. RESULTS: Compared to placebo, tiotropium had larger impact on pulmonary function (FEV(1)+0.164L, FVC +0.112L, RV -0.544L after tiotropium, FEV(1)+0.084L, FVC -0.039L, RV -0.036L after placebo). The addition of tiotropium allowed a longer distance walked in 6min (82.3m vs. 67.7m after placebo) and reduced dyspnoea (Borg score) (-0.4 vs. +0.18 after placebo) when compared with baseline (pre pulmonary rehabilitation program). The changes in SGRQ from baseline to the end of treatment were: total score -28.3U, activity -27.8U, impact -14.5U, and symptoms -33.4U in the placebo group; and total score -19.1U, activity -18.9U, impact -16.4U, and symptoms -33.8U in the tiotropium group. CONCLUSIONS: Our study clearly indicates that there is an advantage in combining pulmonary rehabilitation with an aggressive drug therapy in more severe patient

Self-Evolving Petri Nets

Nowadays, software evolution is a very hot topic. It is particularly complex when it regards critical and nonstopping systems. Usually, these situations are tackled by hard-coding all the foreseeable evolutions in the application design and code. Neglecting the obvious difficulties in pursuing this approach, we also get the application code and design polluted with details that do not regard the current system functionality, and that hamper design analysis, code reuse and application maintenance in general. Petri Nets (PN), as a formalism for modeling and designing distributed/concurrent software systems, are not exempt from this issue. The goal of this work is to propose a PN based reflective framework that lets everyone model a system able to evolve, keeping separated functional aspects from evolutionary ones and applying evolution to the model only if necessary. Such an approach tries to keep system's model as simple as possible, preserving (and exploiting) ability of formally verifying system properties typical of PN, granting at the same time adaptability

Rapid onset of bronchodilation with formoterol/beclomethasone Modulite and formoterol/budesonide Turbuhaler as compared to formoterol alone in patients with COPD

In the present study, we examined whether there is a difference in the onset of bronchodilatation between formoterol/beclomethasone 12/200 μg Modulite and formoterol/budesonide 9/320 μg Turbuhaler in patients with COPD. We enrolled 28 patients with stable COPD. Both formoterol/beclomethasone and formoterol/budesonide elicited a larger mean FEV1–AUC0−15min than formoterol alone, whereas there was no significant difference between their FEV1–AUC0−15min. Also the change in FEV1 15 min after inhalation of formoterol/beclomethasone combination or formoterol/budesonide combination was greater than that induced by formoterol alone. This study confirms the rapid effect of the inhaled corticosteroid component when combined with formoterol and indicates that the onset of bronchodilation of formoterol/beclomethasone Modulite and formoterol/budesonide Turbuhaler are similar and greater than formoterol alone in patients with COPD

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

Isolated airway smooth muscle has been extensively investigated since 1840 to understand the pharmacology of airway diseases. There has often been poor predictability from murine experiments to drugs evaluated in patients with asthma or chronic obstructive pulmonary disease (COPD). However, the use of isolated human airways represents a sensible strategy to optimise the development of innovative molecules for the treatment of respiratory diseases. This review aims to provide updated evidence on the current uses of isolated human airways in validated in vitro methods to investigate drugs in development for the treatment of chronic obstructive respiratory disorders. This review also provides historical notes on the pioneering pharmacological research on isolated human airway tissues, the key differences between human and animal airways, as well as the pivotal differences between human medium bronchi and small airways. Experiments carried out with isolated human bronchial tissues in vitro and ex vivo replicate many of the main anatomical, pathophysiological, mechanical and immunological characteristics of patients with asthma or COPD. In vitro models of asthma and COPD using isolated human airways can provide information that is directly translatable into humans with obstructive lung diseases. Regardless of the technique used to investigate drugs for the treatment of chronic obstructive respiratory disorders (i.e., isolated organ bath systems, videomicroscopy and wire myography), the most limiting factors to produce high-quality and repeatable data remain closely tied to the manual skills of the researcher conducting experiments and the availability of suitable tissue

Clinically Important Deterioration (CID) and Ageing in COPD: A Systematic Review and Meta-Regression Analysis According to PRISMA Statement

purpose: clinically important deterioration (CID) is a composite endpoint developed to quantify the impact of pharmacological treatment in clinical trials for chronic obstructive pulmonary disease (COPD), also showing a prognostic value. CID is defined as any of the following condition: forced expiratory volume in 1 s decrease ≥100 mL from baseline, and/or St. george's respiratory questionnaire total score increase ≥4-unit from baseline, and/or the occurrence of a moderate-to-severe exacerbation of COPD. although most COPD patients experience a clinical worsening as they get older, to date, no specific studies assessed the correlation between ageing and CID in COPD. therefore, the aim of this study was to investigate the impact of ageing on CID in COPD patients. patients and methods: data obtained from 55219 COPD patients were extracted from 17 papers, mostly post-hoc analyses. a pairwise meta-analysis and a meta-regression analysis were performed according to PRISMA-P guidelines to quantify the impact of pharmacological therapy on CID and to determine whether ageing might modulate the risk of CID in COPD patients. results: Inhaled treatments resulted generally effective in reducing the risk of CID in COPD (relative risk: 0.81, 95% confidence interval 0.79-0.84; P &lt; 0.001). the meta-regression analysis indicated a trend toward significance (P = 0.063) in the linear relationship between age and the risk of CID. Of note, age significantly (P &lt; 0.05) increased the risk of CID when associated with lower post-bronchodilator FEV1. these results were not affected by a significant risk of bias. conclusion: this quantitative synthesis suggests that inhaled therapy is effective in reducing the risk of CID in COPD, although such a protective effect may be affected in older patients with impaired lung function. further studies specifically designed on CID in COPD are needed to confirm these results