Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ...ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes.
A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations.
Based on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made.
The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.
Background Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications ...have not been defined. Objective We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function. Methods NET protein complexes (DNA-elastase and histone-elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome. Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation. Results Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale ( P < .0001). This relationship was due to modest correlations between NET complexes and FEV1 , symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations ( P = .002). Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity ( P = .009) and dominance of Haemophilus species operational taxonomic units ( P = .01). Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes. Consistent results were observed regardless of the method of quantifying sputum NETs. Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD. Conclusion NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity.
Bronchiectasis guidelines recommend long-term macrolide treatment for patients with three or more exacerbations per year without Pseudomonas aeruginosa infection. Randomised controlled trials suggest ...that long-term macrolide treatment can prevent exacerbations in adult patients with bronchiectasis, but these individual studies have been too small to do meaningful subgroup analyses. We did a systematic review and individual patient data (IPD) meta-analysis to explore macrolide benefit in subpopulations, including those in which macrolide therapy is not currently recommended.
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science from Jan 1, 2000, to Sept 30, 2018, to identify double blind, randomised, placebo-controlled trials of macrolide antibiotics in adult patients with bronchiectasis. We applied no language restrictions. Randomised controlled trials were eligible if treatment was defined a priori as long term and had a primary or secondary outcome of bronchiectasis exacerbations. Studies in patients with cystic fibrosis bronchiectasis were excluded. The primary outcome of the meta-analysis was frequency of exacerbations requiring treatment with antibiotics. Secondary endpoints were time to first exacerbation, change in quality of life according to the St George's Respiratory Questionnaire (SGRQ), and change in FEV
. IPD meta-analysis was done using fixed effects models adjusting for age, sex, FEV
, and trial. We did prespecified subgroup analyses for each of the primary and secondary endpoints using one-step meta-analysis only. Subgroups were defined by age, sex, previous exacerbation frequency, smoking status, inhaled corticosteroid use at baseline, body-mass index at baseline, cause, C-reactive protein at baseline, baseline FEV
percentage of predicted, SGRQ total score, and Pseudomonas aeruginosa in sputum culture at baseline. The meta-analysis is registered with the PROSPERO international register of systematic reviews, number CRD42018102908.
Of 234 identified studies, we included three randomised controlled trials, and IPD was obtained for 341 participants. Macrolide antibiotics reduced the frequency of exacerbations (adjusted incidence rate ratio IRR 0·49, 95% CI 0·36 to 0·66; p<0·0001). We also found that macrolide treatment improved the time to first exacerbation (adjusted hazard ratio 0·46, 0·34 to 0·61; p<0·0001) and was associated with improved quality of life measured by the SGRQ (mean improvement 2·93 points, 0·03 to 5·83; p=0·048). Macrolides were not associated with a significant improvement in FEV
(67 mL at 1 year, -22 to 112; p=0·14). Effect estimates in prespecified subgroup analyses revealed a reduced frequency of exacerbations in all prespecified subgroups, including a high level of benefit in patients with P aeruginosa infection (IRR 0·36, 0·18-0·72; p=0·0044) and in patients with one to two exacerbations per year (0·37, 0·16-0·88; p=0·025). Studies were rated as low risk of bias across all domains.
Long-term macrolide treatment significantly reduces the frequency of exacerbations in patients with bronchiectasis, with similar benefits observed in all subgroups based on patient characteristics. This finding suggests that macrolides might be considered in patients in whom macrolides are not indicated according to the current guidelines, particularly if alternative approaches to reduce exacerbations have been unsuccessful. However, downsides of long-term macrolide treatment must also be taken into account.
European Respiratory Society.
Although use of inhaled antibiotics is the standard of care in cystic fibrosis, there is insufficient evidence to support use of inhaled antibiotics in patients with bronchiectasis not due to cystic ...fibrosis. We aimed to assess the efficacy and safety of inhaled antibiotics for the long-term treatment of adults with bronchiectasis and chronic respiratory tract infections.
We did a systematic review and meta-analysis of all randomised controlled trials of inhaled-antibiotic use in adult patients with bronchiectasis and chronic respiratory tract infections. Eligible publications were identified by searching MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov. Randomised controlled trials of inhaled antibiotics were included if the patients were adults with stable bronchiectasis diagnosed by CT or bronchography, the trials had treatment a duration of at least 4 weeks, and their outcomes met at least one of the endpoints of interest. Studies in cystic fibrosis were excluded. Efficacy endpoints assessed were bacterial load, bacterial eradication from sputum, frequency of exacerbations, time to first exacerbation, proportion of patients with at least one exacerbation, frequency of severe exacerbations, quality of life, change in FEV
, 6-min walk distance, mortality, adherence to treatment, and sputum volume; safety endpoints were adverse events and bacterial resistance in sputum. Each study was independently reviewed for methodological quality using the Cochrane risk of bias tool. Random-effects meta-analysis was used to pool individual studies. Heterogeneity was assessed using I
. The review is registered on PROSPERO, number CRD42019122892.
16 trials (n=2597 patients) were included for analysis. The mean reduction of colony forming units per g of sputum with inhaled antibiotics was -2·32 log units (95% CI -3·20 to -1·45; p<0·0001). Bacterial eradication was increased with inhaled antibiotic therapy (odds ratio OR 3·36, 1·63 to 6·91; p=0·0010). Inhaled antibiotics significantly reduced exacerbation frequency (rate ratio 0·81, 0·67 to 0·97; p=0·020). Time to first exacerbation was significantly prolonged with inhaled antibiotics (hazard ratio 0·83, 0·69 to 0·99; p=0·028). The proportion of patients with at least one exacerbation decreased (risk ratio 0·85, 0·74 to 0·97; p=0·015). There was a significant reduction in the frequency of severe exacerbations (rate ratio 0·43, 0·24 to 0·78; p=0·0050). The scores for neither the Quality of Life Bronchiectasis questionnaire nor St George's Respiratory Questionnaire improved above the minimal clinically important difference. The relative change in FEV
was a deterioration of 0·87% predicted value (-2·00 to 0·26%; p=0·13). Other efficacy endpoints were reported in only few studies or had few events. There was no difference in treatment-emergent adverse effects (OR 0·97, 0·67 to 1·40; p=0·85) or bronchospasm (0·99, 0·66 to 1·48; p=0·95). Emergence of bacterial resistance was evident at the end of the treatment period (risk ratio 1·91, 1·46 to 2·49; p<0·0001).
Inhaled antibiotics are well tolerated, reduce bacterial load, and achieve a small but statistically significant reduction in exacerbation frequency without clinically significant improvements in quality of life in patients with bronchiectasis and chronic respiratory tract infections.
British Lung Foundation through the GSK/British Lung Foundation Chair of Respiratory Research and European Respiratory Society through the EMBARC2 consortium. EMBARC2 is supported by project partners Chiesi, Grifols, Insmed, Novartis, and Zambon.
Ginger has been proposed as an adjuvant treatment for chemotherapy-induced nausea and vomiting.
The aim of this systematic review with meta-analyses is to evaluate, in adult cancer patients receiving ...chemotherapy, the effects of ginger supplementation dose and duration on the incidence, duration, and severity of chemotherapy-induced nausea and vomiting and outcomes related to chemotherapy-induced nausea and vomiting (eg, quality of life and fatigue), compared with placebo or standard antiemetic medication.
Five electronic databases were searched from database inception to April 2018. The quality of evidence was appraised with the Cochrane Risk of Bias tool and Grading of Recommendations, Assessment, Development, and Evaluation level. Data were pooled using Revman software.
Eighteen articles were analyzed. The likelihood of acute vomiting was reduced by 60% with ginger supplementation ≤1 g/day for duration >3 days, compared with control groups (odds ratio 0.4, 95% CI 0.17 to 0.81; P=0.01; n=3 studies; n=3 interventions; n=301 participants; I
=20%; Grading of Recommendations, Assessment, Development, and Evaluation level: Moderate). The likelihood of fatigue was reduced by 80% with ginger supplementation of any dose for duration <3 days (odds ratio 0.2, 95% CI, 0.03 to 0.87; P=0.03; n=1 studies; n=2 interventions; n=219 participants; I
=0%; Grading of Recommendations, Assessment, Development, and Evaluation level: Low). No statistically significant association was found between ginger and likelihood of overall or delayed vomiting, likelihood or severity of nausea, or other outcomes related to chemotherapy-induced nausea and vomiting.
Ginger supplementation might benefit chemotherapy-induced vomiting as well as fatigue. Due to clinical heterogeneity, this systematic review update found no association between ginger and chemotherapy-induced nausea and other chemotherapy-induced nausea and vomiting-related outcomes. The results of this systematic review and meta-analysis provide a rationale for further research with stronger study designs, adequate sample sizes, standardized ginger products, and validated outcome measures to confirm efficacy of ginger supplementation and optimal dosing regimens.
Abstract
Background
Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life ...clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).
Methods
In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy.
Results
178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/μL (IQR 4000-7000cells/μL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py,
P
< 0.001) than those with BNC in the normal range (2000-6000cells/μL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33%
P
< 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs. 5%, P < 0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (
N
= 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity.
Conclusion
High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.
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