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Respiratory Medicine Nov 2022This network meta-analysis (NMA) compared fixed-dose, twice daily fluticasone propionate/salmeterol (FP/Sal) vs. inhaled corticosteroid (ICS) and other ICS/long-acting... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This network meta-analysis (NMA) compared fixed-dose, twice daily fluticasone propionate/salmeterol (FP/Sal) vs. inhaled corticosteroid (ICS) and other ICS/long-acting beta-agonists (LABA) treatments, including when administered using maintenance and reliever therapy (MART) regimens, in terms of improvements in health-related quality of life (HRQoL). The relationship between changes in asthma control and HRQoL was assessed.
METHODS
Articles published between 2001 and 2021, reporting change from baseline (CFB) in Asthma Quality of Life Questionnaire (AQLQ) in patients with moderate-to-severe asthma, were identified by a systematic review. Random effects Bayesian NMAs derived estimates of the mean difference in CFB in AQLQ vs. other interventions connected to the network (included 15 studies). Sensitivity analyses explored the impacts of differences in follow-up duration, baseline asthma control, the inclusion of observational studies, adjusting for baseline FEV, and low-medium ICS dose arms only. Linear regression analysis compared CFBs in AQLQ and Asthma Control Questionnaire (ACQ) score.
RESULTS
Mean CFB in AQLQ with FP/Sal vs. comparators demonstrated expected ranked effects: mean difference 0.65 [95% credible interval: 0.54, 0.78] versus placebo, 0.58 [ 0.33, 0.84] versus LABA, 0.21 [ 0.13, 0.31] versus ICS alone, 0.06 [-0.04, 0.19] versus other ICS/LABA, and 0.00 [-0.13, 0.14] versus ICS/formoterol MART. Sensitivity analyses largely showed consistent results. Improvements in AQLQ and ACQ were strongly correlated (R = 0.94).
CONCLUSIONS
This NMA demonstrates that HRQoL is responsive to treatment, is strongly related to asthma control and that it can be well-managed in patients with moderate-to-severe asthma using regular treatment with inhaled FP/Sal.
Topics: Humans; Fluticasone-Salmeterol Drug Combination; Quality of Life; Bronchodilator Agents; Network Meta-Analysis; Bayes Theorem; Administration, Inhalation; Asthma; Formoterol Fumarate; Adrenal Cortex Hormones; Fluticasone; Drug Combinations
PubMed: 36257125
DOI: 10.1016/j.rmed.2022.106993 -
Respiratory Medicine Jul 2010The management of cough in adults with respiratory and non-respiratory illnesses is suboptimal and based mostly on clinical opinions rather than evidence. A systematic... (Review)
Review
The management of cough in adults with respiratory and non-respiratory illnesses is suboptimal and based mostly on clinical opinions rather than evidence. A systematic review was carried out assessing all trials in adult patients with respiratory and non-respiratory diseases (excluding cancer) that had chronic cough as primary or secondary outcome. A total of 1177 trials were retrieved and 75 met the criteria for inclusion in the review. The vast majority were in patients with asthma and chronic obstructive pulmonary disease (COPD). Cough was the primary outcome in less than one-quarter of the studies. The measurement of cough was variable, mostly using unvalidated scales or being part of an overall 'symptoms' score. Positive results were overall seen with the use of corticosteroids, leukotriene receptor antagonists, mast cell stabilizers, ipratropium bromide, neltenexine, iodinised glycerol and lidocaine. Speech pathology training and symptom monitoring through SMS messages (accompanied by treatment adjustments) have also shown promise. Evidence for established anti-tussive agents such as codeine was scarce, with positive studies from the 1960s, whilst more recent studies showed no effect in patients with COPD. Many studies had conflicting results. It is imperative that the management of cough and its evidence base be improved, using higher quality research designs and with cough being the primary outcome of trials.
Topics: Adrenal Cortex Hormones; Adult; Antitussive Agents; Asthma; Bronchodilator Agents; Chronic Disease; Cough; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic
PubMed: 20385478
DOI: 10.1016/j.rmed.2010.02.010 -
Surfactant therapy for acute respiratory failure in children: a systematic review and meta-analysis.Critical Care (London, England) 2007Exogenous surfactant is used to treat acute respiratory failure in children, although the benefits and harms in this setting are not clear. The objective of the present... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
Exogenous surfactant is used to treat acute respiratory failure in children, although the benefits and harms in this setting are not clear. The objective of the present systematic review is to assess the effect of exogenous pulmonary surfactant on all-cause mortality in children mechanically ventilated for acute respiratory failure.
METHODS
We searched the MEDLINE, EMBASE, CINAHL and Ovid Healthstar databases, the bibliographies of included trials and review articles, conference proceedings and trial registries. We included prospective, randomized, controlled trials of pulmonary surfactant that enrolled intubated and mechanically ventilated children with acute respiratory failure. We excluded trials that exclusively enrolled neonates or patients with asthma. Two reviewers independently rated trials for inclusion, extracted data and assessed the methodologic quality. We quantitatively pooled the results of trials, where suitable, using a random effects model.
RESULTS
Six trials randomizing 314 patients were included. Surfactant use reduced mortality (relative risk = 0.7, 95% confidence interval = 0.4 to 0.97, P = 0.04), was associated with increased ventilator-free days (weighted mean difference = 2.5 days, 95% confidence interval = 0.3 to 4.6 days, P = 0.02) and reduced the duration of ventilation (weighted mean difference = 2.3 days, 95% confidence interval = 0.1 to 4.4 days, P = 0.04).
CONCLUSION
Surfactant use decreased mortality, was associated with more ventilator-free days and reduced the duration of ventilation. No serious adverse events were reported.
Topics: Child; Humans; Intensive Care Units, Pediatric; Length of Stay; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome; Survival Analysis; Treatment Outcome
PubMed: 17573963
DOI: 10.1186/cc5944 -
The Cochrane Database of Systematic... Sep 2017This review is the first update of a previously published review in The Cochrane Library (Issue 7, 2015). Interleukin-5 (IL-5) is the main cytokine involved in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is the first update of a previously published review in The Cochrane Library (Issue 7, 2015). Interleukin-5 (IL-5) is the main cytokine involved in the activation of eosinophils, which cause airway inflammation and are a classic feature of asthma. Monoclonal antibodies targeting IL-5 or its receptor (IL-5R) have been developed, with recent studies suggesting that they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function. These are being incorporated into asthma guidelines.
OBJECTIVES
To compare the effects of therapies targeting IL-5 signalling (anti-IL-5 or anti-IL-5Rα) with placebo on exacerbations, health-related qualify of life (HRQoL) measures, and lung function in adults and children with chronic asthma, and specifically in those with eosinophilic asthma refractory to existing treatments.
SEARCH METHODS
We searched the Cochrane Airways Trials Register, clinical trials registries, manufacturers' websites, and reference lists of included studies. The most recent search was March 2017.
SELECTION CRITERIA
We included randomised controlled trials comparing mepolizumab, reslizumab and benralizumab versus placebo in adults and children with asthma.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and analysed outcomes using a random-effects model. We used standard methods expected by Cochrane.
MAIN RESULTS
Thirteen studies on 6000 participants met the inclusion criteria. Four used mepolizumab, four used reslizumab, and five used benralizumab. One study in benralizumab was terminated early due to sponsor decision and contributed no data. The studies were predominantly on people with severe eosinophilic asthma, which was similarly but variably defined. Eight included children over 12 years but these results were not reported separately. We deemed the risk of bias to be low, with all studies contributing data being of robust methodology. We considered the quality of the evidence for all comparisons to be high overall using the GRADE scheme, with the exception of intravenous mepolizumab because this is not currently a licensed delivery route.All of the anti-IL-5 treatments assessed reduced rates of 'clinically significant' asthma exacerbation (defined by treatment with systemic corticosteroids for three days or more) by approximately half in participants with severe eosinophilic asthma on standard of care (at least medium-dose inhaled corticosteroids (ICS)) with poorly controlled disease (either two or more exacerbations in the preceding year or Asthma Control Questionnaire (ACQ) 1.5 or more). Non-eosinophilic participants treated with benralizumab also showed a significant reduction in exacerbation rates, but no data were available for non-eosinophilic participants, and mepolizumab or reslizumab.We saw modest improvements in validated HRQoL scores with all anti-IL-5 agents in severe eosinophilic asthma. However these did not exceed the minimum clinically important difference for ACQ and Asthma Quality of Life Questionnaire (AQLQ), with St. George's Respiratory Questionnaire (SGRQ) only assessed in two studies. The improvement in HRQoL scores in non-eosinophilic participants treated with benralizumab, the only intervention for which data were available in this subset, was not statistically significant, but the test for subgroup difference was negative.All anti-IL-5 treatments produced a small but statistically significant improvement in mean pre-bronchodilator forced expiratory flow in one second (FEV) of between 0.08 L and 0.11 L.There were no excess serious adverse events with any anti-IL-5 treatment, and indeed a reduction in favour of mepolizumab that could be due to a beneficial effect on asthma-related serious adverse events. There was no difference compared to placebo in adverse events leading to discontinuation with mepolizumab or reslizumab, but significantly more discontinued benralizumab than placebo, although the absolute numbers were small (36/1599 benralizumab versus 9/998 placebo).Mepolizumab, reslizumab and benralizumab all markedly reduced blood eosinophils, but benralizumab resulted in almost complete depletion, whereas a small number remained with mepolizumab and reslizumab. The implications for efficacy and/or adverse events are unclear.
AUTHORS' CONCLUSIONS
Overall our study supports the use of anti-IL-5 treatments as an adjunct to standard of care in people with severe eosinophilic asthma and poor control. These treatments roughly halve the rate of asthma exacerbations in this population. There is limited evidence for improved HRQoL scores and lung function, which may not meet clinically detectable levels. There were no safety concerns regarding mepolizumab or reslizumab, and no excess serious adverse events with benralizumab, although there remains a question over adverse events significant enough to prompt discontinuation.Further research is needed on biomarkers for assessing treatment response, optimal duration and long-term effects of treatment, risk of relapse on withdrawal, non-eosinophilic patients, children (particularly under 12 years), and comparing anti-IL-5 treatments to each other and, in people eligible for both, to anti-immunoglobulin E. For benralizumab, future studies should closely monitor rates of adverse events prompting discontinuation.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Child; Disease Progression; Humans; Injections, Intravenous; Injections, Subcutaneous; Interleukin-5; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Interleukin-5
PubMed: 28933516
DOI: 10.1002/14651858.CD010834.pub3 -
Advances in Therapy Jul 2023Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC).... (Review)
Review
INTRODUCTION
Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC). In the absence of head-to-head trials, we describe the effects of biologics on annualized asthma exacerbation rate (AAER) by baseline BEC in placebo-controlled RCTs. Exacerbations associated with hospitalization or an emergency room visit, pre-bronchodilator forced expiratory volume in 1 s, Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score were also summarized.
METHODS
MEDLINE (via PubMed) was searched for RCTs of biologics in patients with severe, uncontrolled asthma and with AAER reduction as a primary or secondary endpoint. AAER ratios and change from baseline in other outcomes versus placebo were compared across baseline BEC subgroups. Analysis was limited to US Food and Drug Administration-approved biologics.
RESULTS
In patients with baseline BEC ≥ 300 cells/μL, AAER reduction was demonstrated with all biologics, and other outcomes were generally improved. In patients with BEC 0 to < 300 cells/μL, consistent AAER reduction was demonstrated only with tezepelumab; improvements in other outcomes were inconsistent across biologics. In patients with BEC 150 to < 300 cells/μL, consistent AAER reduction was demonstrated with tezepelumab and dupilumab (300 mg dose only), and in those with BEC 0 to < 150 cells/μL, AAER reduction was demonstrated only with tezepelumab.
CONCLUSION
The efficacy of all biologics in reducing AAER in patients with severe asthma increases with higher baseline BEC, with varying profiles across individual biologics likely due to differing mechanisms of action.
Topics: Humans; Eosinophils; Anti-Asthmatic Agents; Biological Products; Asthma; Leukocyte Count; Eosinophilia; Double-Blind Method
PubMed: 37233876
DOI: 10.1007/s12325-023-02514-0 -
European Respiratory Review : An... Dec 2017Poor inhaler technique and inferior asthma outcomes are evident in older adults. Reviews comparing metered dose inhaler (MDI) and dry powder inhaler (DPI) techniques... (Review)
Review
Poor inhaler technique and inferior asthma outcomes are evident in older adults. Reviews comparing metered dose inhaler (MDI) and dry powder inhaler (DPI) techniques across older adults and younger cohorts are scarce. This systematic review aimed to determine whether differences exist between such cohorts with regards to the number and type of MDI and DPI errors made. A systematic literature search was conducted in Embase, Medline and PubMed from July 1 to December 31, 2016. Studies were selected in accordance with preset inclusion criteria, relevant data were extracted, and quality was assessed with validated checklists. 14 studies were identified. Evidence suggests a negative correlation between advancing age and correct technique across MDI and varying DPI devices when examined collectively. Differences appear to exist between older adult and younger cohorts prescribed MDIs in error types. There is evidence of age-associated differences in the number and type of inhaler technique errors. Further research is required to assess outcomes in individual DPIs, reproducibility and the effects of confounders.
Topics: Administration, Inhalation; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Child; Dry Powder Inhalers; Equipment Design; Health Knowledge, Attitudes, Practice; Humans; Lung; Metered Dose Inhalers; Middle Aged; Patient Education as Topic; Self Administration; Young Adult
PubMed: 29212836
DOI: 10.1183/16000617.0055-2017 -
Annals of Agricultural and... Mar 2017Year after year, we spend an increasing amount of time in a sitting position. Often, we sit with poor posture, as indicated by numerous pain syndromes within the... (Review)
Review
INTRODUCTION
Year after year, we spend an increasing amount of time in a sitting position. Often, we sit with poor posture, as indicated by numerous pain syndromes within the musculoskeletal system. Several reports confirm that body posture and the amount of time spent in a seated position have extensive implications for our health. Previous studies and a literature review suggest there is limited knowledge regarding an ergonomic sitting position.
OBJECTIVE
The aim of the study was to analyze the research relating to a proper sitting position and the consequences of incorrect sitting posture. A database search was conducted in Science Direct, Scopus, PubMed, Medline, and Google Scholar. Selection was made on the basis of titles, the abstracts and full texts of the studies. No limits were applied to the date of publication.
CONCLUSIONS
Incorrect sitting posture contributes to many disorders, especially in the cervical and lumbar spine. It also determines the work of the respiratory system. Most authors suggest that maintenance of the physiological curvature of the spine is crucial for the biomechanics of the sitting position, as well as the location of the head and position of the pelvis. It raises awareness of work-related hazards and the introduction of education on the principles of proper seating. It is necessary to draw attention to the risks associated with work performed in a sitting posture, and education on the principles of ergonomical sitting.
Topics: Cervical Vertebrae; Ergonomics; Lumbar Vertebrae; Musculoskeletal System; Posture; Respiratory System
PubMed: 28378964
DOI: 10.5604/12321966.1227647 -
International Journal of Environmental... Nov 2022The detrimental effects of PM and PM (particulate matter less than 2.5 or 10 μm) on human respiratory system, including lung function, have been widely assessed.... (Meta-Analysis)
Meta-Analysis Review
The detrimental effects of PM and PM (particulate matter less than 2.5 or 10 μm) on human respiratory system, including lung function, have been widely assessed. However, the associations between PM (particulate matter of less than 1 μm) and lung function in children and adolescents are less explored, and current evidence is inconsistent. We conducted a meta-analysis of the literature on the association between PM and lung function in children and adolescents to fill this gap. With no date or language constraints, we used a combination of MeSH (Medical Subject Headings) terms and free text to search PubMed, EMBASE and Web of Science databases through, 1 October 2022 for "PM exposure" and "lung function". A total of 6420 relevant studies were identified through our initial search, and seven studies were included in our study. In this meta-analysis, the fixed effect and random effects statistical models were used to estimate the synthesized effects of the seven included studies. For every 10 μg/m increase in short-term PM exposure, forced vital capacity (FVC), forced expiratory volume in the first second (FEV), peak expiratory flow (PEF) and maximal mid-expiratory flow (MMEF) decreased by 31.82 mL (95% CI: 20.18, 43.45), 32.28 mL (95% CI: 16.73, 48.91), 36.85 mL/s (95% CI: 15.33, 58.38) and 34.51 mL/s (95% CI: 19.61, 49.41), respectively. For each 10 μg/m increase in long-term PM exposure, FVC, FEV, PEF and MMEF decreased by 102.34 mL (95% CI: 49.30, 155.38), 75.17 mL (95% CI: 39.61, 110.73), 119.01 mL/s (95% CI: 72.14, 165.88) and 44.94 mL/s (95% CI: 4.70, 85.18), respectively. Our study provides further scientific evidence for the harmful effects of PM exposure on lung function in children and adolescents, indicating that exposure to PM is detrimental to pulmonary health. To reduce the adverse health effects of air pollution on children and adolescents, effective preventive measures should be taken.
Topics: Child; Adolescent; Humans; Air Pollutants; Environmental Exposure; Particulate Matter; Air Pollution; Lung
PubMed: 36497960
DOI: 10.3390/ijerph192315888 -
Revista Espanola de Quimioterapia :... Oct 2022Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few...
A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria.
OBJECTIVE
Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation.
METHODS
A systematic literature review was developed to identify RFs associated with infection progression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert's experience.
RESULTS
A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation.
CONCLUSIONS
The results of this study may contribute to the early identification of CRGNB colonized patients at higher risk of infection development, favouring time-to-effective therapy and improving health outcomes.
Topics: Adult; Anti-Bacterial Agents; Carbapenems; Consensus; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Pneumonia; Respiratory System; Risk Factors
PubMed: 35859521
DOI: 10.37201/req/062.2022 -
Forensic Science, Medicine, and... Mar 2023The persistence and infectivity of SARS-CoV-2 in different postmortem COVID-19 specimens remain unclear despite numerous published studies. This information is essential... (Review)
Review
The persistence and infectivity of SARS-CoV-2 in different postmortem COVID-19 specimens remain unclear despite numerous published studies. This information is essential to improve corpses management related to clinical biosafety and viral transmission in medical staff and the public community. We aim to understand SARS-CoV-2 persistence and infectivity in COVID-19 corpses. We conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocols. A systematic literature search was performed in PubMed, Science Direct Scopus, and Google Scholar databases using specific keywords. We critically reviewed the collected studies and selected the articles that met the criteria. We included 33 scientific papers that involved 491 COVID-19 corpses. The persistence rate and maximum postmortem interval (PMI) range of the SARS-CoV-2 findings were reported in the lungs (138/155, 89.0%; 4 months), followed by the vitreous humor (7/37, 18.9%; 3 months), nasopharynx/oropharynx (156/248, 62.9%; 41 days), abdominal organs (67/110, 60.9%; 17 days), skin (14/24, 58.3%; 17 days), brain (14/31, 45.2%; 17 days), bone marrow (2/2, 100%; 12 days), heart (31/69, 44.9%; 6 days), muscle tissues (9/83, 10.8%; 6 days), trachea (9/20, 45.0%; 5 days), and perioral tissues (21/24, 87.5%; 3.5 days). SARS-CoV-2 infectivity rates in viral culture studies were detected in the lungs (9/15, 60%), trachea (2/4, 50%), oropharynx (1/4, 25%), and perioral (1/4, 25%) at a maximum PMI range of 17 days. The SARS-CoV-2 persists in the human body months after death and should be infectious for weeks. This data should be helpful for postmortem COVID-19 management and viral transmission preventive strategy.
Topics: Humans; COVID-19; SARS-CoV-2; Oropharynx; Nasopharynx; Cadaver
PubMed: 36001241
DOI: 10.1007/s12024-022-00518-w