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Use of oral Glucocorticoids and the Risk of Pulmonary Embolism: A Population-Based Case-Control Study.

Chest. 2012 Dec 20;

Authors: Stuijver DJ, Majoor CJ, van Zaane B, Souverein PC, de Boer A, Dekkers OM, Büller HR, Gerdes VE

Abstract
ABSTRACT BACKGROUND: Recently, endogenous glucocorticoid excess has been identified as risk factor for venous thromboembolism. Whether exogenous use of glucocorticoids is associated with an increased risk of VTE is unclear. We aimed to quantify the risk of symptomatic pulmonary embolism (PE) in patients using corticosteroids. METHODS: A case-control study was conducted using the PHARMO Record Linkage System, a Dutch population-based pharmacy registry. Cases were 4495 patients with a first hospital admission for PE between 1998 and 2008. Controls were 16802 gender- and age-matched subjects without a history of PE. By using ICD codes for hospitalization, information on underlying conditions was retrieved. RESULTS: The risk of PE was highest in the first 30 days of glucocorticoid exposure with an adjusted OR of 5.9 (95%CI 2.3-3.9) and gradually decreased with increasing duration of use to an OR of 1.9 (95%CI 1.3-2.9) for chronic users (>1 year). Low dose glucocorticoid use (prednisolon daily dose equivalent < 5 mg) carried a 2-fold increased risk of PE (OR 1.8, 95% CI 1.3-2.4), whereas a 10-fold increased risk was observed for the highest dose of glucocorticoids (>30 mg prednisolon) (OR 9.6, 95% CI 4.3-20.5). Stratification for both duration and dose of glucocorticoid use showed the highest risk of PE in recently started users as compared to chronic users at the time of PE, irrespective of the dose. CONCLUSION: Patients treated with oral glucocorticoids may be at increased risk of pulmonary embolism, especially during the first month of exposure. This hypothesis requires confirmation in future studies.

PMID: 23258429 [PubMed - as supplied by publisher]

Risk of deep-vein thrombosis and pulmonary embolism in asthma.

Eur Respir J. 2012 Dec 20;

Authors: Majoor CJ, Kamphuisen PW, Zwinderman AH, Ten Brinke A, Amelink M, Rijssenbeek-Nouwens L, Sterk PJ, Büller HR, Bel EH

Abstract
Increasing evidence suggests that patients with asthma have activated coagulation within the airways. Whether this leads to an increase in venous thromboembolic events (VTE) is unknown. We therefore assessed the incidence of VTE in patients with mild-moderate and severe asthma as compared to an age- and gender-matched reference population.648 patients with asthma (283 with severe and 365 patients with mild-moderate asthma) visiting 3 Dutch outpatient asthma clinics were studied. All patients completed a questionnaire about a diagnosis of deep-vein thrombosis (DVT) and pulmonary embolism (PE) in the past, their risk factors, history of asthma and medication use. All VTE were objectively verified.In total, 35 VTE events (16 DVT and 19 PE) occurred at a median age of 39 (range 20-63) years. The incidence of PE in patients with severe asthma was 0.93 (95% Confidence Interval (CI): 0.42-1.44) per 1000 person-years, 0.33 (95%CI: 0.07-0.60) in mild-moderate asthma, and 0.18 (95%CI: 0.03-0.33) in the general population, respectively. Severe asthma and oral corticosteroid use were independent risk factors of PE (hazard ratios: 3.33 (1.16-9.93) and 2.82 (1.09-7.30), respectively). Asthma was not associated with DVT.Severe asthma greatly enhances the risk of pulmonary embolism, particularly if chronic corticosteroids are used.

PMID: 23258790 [PubMed - as supplied by publisher]

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Early use of inhaled corticosteroids in the emergency department treatment of acute asthma.

Cochrane Database Syst Rev. 2012;12:CD002308

Authors: Edmonds ML, Milan SJ, Camargo CA, Pollack CV, Rowe BH

Abstract
BACKGROUND: Systemic corticosteroid therapy is central to the management of acute asthma. The use of inhaled corticosteroids (ICS) may also be beneficial in this setting.
OBJECTIVES: To determine the benefit of ICS for the treatment of patients with acute asthma managed in the emergency department (ED).
SEARCH METHODS: We identified controlled clinical trials from the Cochrane Airways Group specialised register of controlled trials. Bibliographies from included studies, known reviews, and texts also were searched. The latest search was September 2012.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs. Studies were included if patients presented to the ED or its equivalent with acute asthma, and were treated with ICS or placebo, in addition to standard therapy. Two review authors independently selected potentially relevant articles, and then independently selected articles for inclusion. Methodological quality was independently assessed by two review authors. There were three different types of studies that were included in this review: 1) studies comparing ICS vs. placebo, with no systemic corticosteroids given to either treatment group, 2) studies comparing ICS vs. placebo, with systemic corticosteroids given to both treatment groups, and 3) studies comparing ICS alone versus systemic corticosteroids. For the analysis, the first two types of studies were included as separate subgroups in the primary analysis (ICS vs. placebo), while the third type of study was included in the secondary analysis (ICS vs. systemic corticosteroid).
DATA COLLECTION AND ANALYSIS: Data were extracted independently by two review authors if the authors were unable to verify the validity of extracted information. Missing data were obtained from the authors or calculated from other data presented in the paper. Where appropriate, individual and pooled dichotomous outcomes were reported as odds ratios (OR) with 95% confidence intervals (CIs). Where appropriate, individual and pooled continuous outcomes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% CIs. The primary analysis employed a fixed-effect model and a random-effects model was used for sensitivity analysis. Heterogeneity is reported using I-squared (I(2)) statistics.
MAIN RESULTS: Twenty trials were selected for inclusion in the primary analysis (13 paediatric, seven adult), with a total number of 1403 patients. Patients treated with ICS were less likely to be admitted to hospital (OR 0.44; 95% CI 0.31 to 0.62; 12 studies; 960 patients) and heterogeneity (I(2) = 27%) was modest. This represents a reduction from 32 to 17 hospital admissions per 100 patients treated with ICS in comparison with placebo. Subgroup analysis of hospital admissions based on concomitant systemic corticosteroid use revealed that both subgroups indicated benefit from ICS in reducing hospital admissions (ICS and systemic corticosteroid versus systemic corticosteroid: OR 0.54; 95% CI 0.36 to 0.81; 5 studies; N = 433; ICS versus placebo: OR 0.27; 95% CI 0.14 to 0.52; 7 studies; N = 527). However, there was moderate heterogeneity in the subgroup using ICS in addition to systemic steroids (I(2) = 52%). Patients receiving ICS demonstrated small, significant improvements in peak expiratory flow (PEF: MD 7%; 95% CI 3% to 11%) and forced expiratory volume in one second (FEV(1): MD 6%; 95% CI 2% to 10%) at three to four hours post treatment). Only a small number of studies reported these outcomes such that they could be included in the meta-analysis and most of the studies in this comparison did not administer systemic corticosteroids to either treatment group. There was no evidence of significant adverse effects from ICS treatment with regard to tremor or nausea and vomiting. In the secondary analysis of studies comparing ICS alone versus systemic corticosteroid alone, heterogeneity among the studies complicated pooling of data or drawing reliable conclusions.
AUTHORS' CONCLUSIONS: ICS therapy reduces hospital admissions in patients with acute asthma who are not treated with oral or intravenous corticosteroids. They may also reduce admissions when they are used in addition to systemic corticosteroids; however, the most recent evidence is conflicting. There is insufficient evidence that ICS therapy results in clinically important changes in pulmonary function or clinical scores when used in acute asthma in addition to systemic corticosteroids. Also, there is insufficient evidence that ICS therapy can be used in place of systemic corticosteroid therapy when treating acute asthma. Further research is needed to clarify the most appropriate drug dosage and delivery device, and to define which patients are most likely to benefit from ICS therapy. Use of similar measures and reporting methods of lung function, and a common, validated, clinical score would be helpful in future versions of this meta-analysis.

PMID: 23235589 [PubMed - in process]

Related Articles

Inhaled magnesium sulfate in the treatment of acute asthma.

Cochrane Database Syst Rev. 2012;12:CD003898

Authors: Powell C, Dwan K, Milan SJ, Beasley R, Hughes R, Knopp-Sihota JA, Rowe BH

Abstract
BACKGROUND: Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO(4)) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO(4) has been demonstrated, little is known of the role of inhaled MgSO(4).
OBJECTIVES: To determine the efficacy of inhaled MgSO(4) administered in acute asthma on pulmonary functions and admission rates.Specific aims: To quantify the effects of inhaled MgSO(4) i) in addition to inhaled β(2)-agonist, ii) in comparison to inhaled β(2)-agonist alone or iii) in addition to combination treatment with inhaled β(2) -agonist and ipratropium bromide.
SEARCH METHODS: Randomised controlled trials were identified from the Cochrane Airways Group register of trials in September 2012. These trials were supplemented with trials found in the reference list of published studies, studies found using extensive electronic search techniques, as well as a review of the grey literature and conference proceedings.
SELECTION CRITERIA: Randomised (or pseudo-randomised) controlled trials including adults or children with acute asthma were eligible for inclusion in the review. Studies were included if patients were treated with nebulised MgSO(4) alone or in combination with β(2)-agonist and/or ipratropium bromide and were compared with β(2)-agonist alone or inactive control.
DATA COLLECTION AND ANALYSIS: Trial selection, data extraction and risk of bias were assessed independently by two review authors. Efforts were made to collect missing data from authors. Results are presented as standardised mean differences (SMD) for pulmonary function and risk ratios (RR) for hospital admission; both are displayed with their 95% confidence intervals (CI).
MAIN RESULTS: Sixteen trials (21 references) of unclear and high risk of bias were eligible and included 896 patients who were randomised (838 patients completed). Seven of the 16 included studies involved adults exclusively, three included adults and paediatric patients, four studies enrolled paediatric patients and in the remaining two studies the age of participants was not stated.The design, definitions, intervention and outcomes were different in all 16 studies; this heterogeneity made direct comparisons difficult (see additional tables 1-3).The overall risk of bias among the included studies was variable and this is reflected in the 'Summary of findings' table with most outcomes being judged as only moderate or less.Inhaled magnesium sulfate in addition to inhaled β(2)-agonistThere was no statistically significant improvement in pulmonary function when inhaled MgSO(4) and β(2)-agonist was compared with β(2)-agonist alone (SMD 0.23; 95% CI -0.27 to 0.74; three studies, n = 188); however, there was considerable between study heterogeneity. There was no clear advantage in terms of hospital admissions (RR 0.76 95% CI 0.49, 1.16; four studies, n = 249), and there were no serious adverse events reported.Inhaled magnesium sulfate versus inhaled β(2)-agonistThe results of pulmonary function in three studies that compared inhaled MgSO(4) versus β(2)-agonist were too heterogeneous to combine; however, two of the studies found poorer lung function on MgSO(4). There was no significant difference in terms of hospital admissions in a single small study when MgSO(4) was compared to β(2)-agonist (RR 0.53 95% CI 0.05, 5.31; one study, n = 33), and there were no serious adverse events reported.Inhaled magnesium sulfate in addition to inhaled β(2)-agonist and ipratropiumA further comparison has been included in the 2012 update of this review of MgSO(4) given in addition to inhaled ipratropium and β(2)-agonist therapy (as recommended by the GINA guidelines). However, there is not yet enough data for this outcome to come to any definite conclusions, but both small studies in adults with severe asthma exacerbation found improvements in pulmonary function with additional inhaled MgSO(4).
AUTHORS' CONCLUSIONS: There is currently no good evidence that inhaled MgSO(4) can be used as a substitute for inhaled β(2)-agonists. When used in addition to inhaled β(2)-agonists (with or without inhaled ipratropium), there is currently no overall clear evidence of improved pulmonary function or reduced hospital admissions. However, individual study results from three trials suggest possible improved pulmonary function in those with severe asthma exacerbations (FEV1 less than 50% predicted). Heterogeneity among trials included in this review precludes a more definitive conclusion. Further studies should focus on inhaled MgSO(4) in addition to the current guideline treatment for acute asthma (inhaled β(2) -agonist and ipratropium bromide). As the evidence suggests that the most effective role of nebulised MgSO(4) may be in those with severe acute features and this is where future research should be focused. A set of core outcomes needs to be agreed upon both in adult and paediatric studies to allow improved study comparison in future. 

PMID: 23235599 [PubMed - in process]