5032 articles - 08.09.10
1: Am J Respir Crit Care Med. 2010 Aug 23; [Epub ahead of print]
Khemani RG, Newth CJ.
Childrenas Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, United States.
Pediatric practitioners face unique challenges when attempting to translate or adapt adult derived evidence regarding ventilation practices for Acute Lung Injury or Acute Respiratory Distress Syndrome into pediatric practice. Fortunately or unfortunately, there appears to be selective adoption of adult practices for pediatric mechanical ventilationamany of which pose considerable challenges or uncertainty when translated to pediatrics. These differences, combined with heterogeneous management strategies within pediatric critical care, can complicate clinical practice and make designing robust clinical trials in pediatric acute respiratory failure particularly difficult. These issues surround the lack of explicit ventilator protocols in pediatrics, either computer or paper based; differences in modes of conventional ventilation and perceived marked differences in the approach to high frequency oscillatory ventilation; challenges with patient recruitment; the shortcomings of the definition of ALI and ARDS; the more reliable yet still somewhat unpredictable relationship between lung injury severity and outcome; and the reliance upon potentially biased surrogate outcome measures like ventilator free days for all pediatric trials. The purpose of this review will be to highlight these challenges, discuss pertinent work which has begun to address them, and propose potential solutions or future investigations which may help facilitate comprehensive trials on pediatric mechanical ventilation and define clinical practice standards.
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PMID: 20732987 [PubMed - as supplied by publisher]2: Thorax. 2010 Aug 20; [Epub ahead of print]
Loke YK, Kwok CS, Niruban A, Myint PK.
School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, Norfolk, UK.
Background Several scoring systems have been used to predict mortality in patients with community-acquired pneumonia. The properties of commonly used risk stratification scales were systematically reviewed. Methods MEDLINE and EMBASE (January 1999-October 2009) were searched for prospective studies that reported mortality at 4-8 weeks in patients with radiographically-confirmed community-acquired pneumonia. The search focused on the Pneumonia Severity Index (PSI) and the three main iterations of the CURB (confusion, urea nitrogen, respiratory rate, blood pressure) scale (CURB-65, CURB, CRB-65), and test performance was evaluated based on 'higher risk' categories as follows: PSI class IV/V, CURB-65 (score >/=3), CURB (score >/=2) and CRB-65 (score >/=2). Random effects meta-analysis was used to generate summary statistics of test performance and receiver operating characteristic curves were used for predicting mortality. Results 402 articles were screened and 23 studies involving 22 753 participants (average mortality 7.4%) were retrieved. The respective diagnostic odds ratios for mortality were 10.77 (PSI), 6.40 (CURB-65), 5.97 (CRB-65) and 5.75 (CURB). Overall, PSI had the highest sensitivity and lowest specificity for mortality, CRB-65 was the most specific (but least sensitive) test and CURB-65/CURB were between the two. Negative predictive values for mortality were similar among the tests, ranging from 0.94 (CRB-65) to 0.98 (PSI), whereas positive predictive values ranged from 0.14 (PSI) to 0.28 (CRB-65). Conclusions The current risk stratification scales (PSI, CURB-65, CRB-65 and CURB) have different strengths and weaknesses. All four scales had good negative predictive values for mortality in populations with a low prevalence of death but were less useful with regard to positive predictive values.
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PMID: 20729235 [PubMed - as supplied by publisher]3: Thorax. 2010 Aug 20; [Epub ahead of print]
Chalmers JD, Singanayagam A, Akram AR, Mandal P, Short PM, Choudhury G, Wood V, Hill AT.
University of Edinburgh, Edinburgh, UK.
Introduction International guidelines recommend a severity-based approach to management in community-acquired pneumonia. CURB65, CRB65 and the Pneumonia Severity Index (PSI) are the most widely recommended severity scores. The aim of this study was to compare the performance characteristics of these scores for predicting mortality in community-acquired pneumonia. Methods A systematic review and meta-analysis was conducted according to MOOSE (meta-analysis of observational studies in epidemiology) guidelines. PUBMED and EMBASE were searched (1980-2009). 40 studies reporting prognostic information for the PSI, CURB65 and CRB65 severity scores were identified. Performance characteristics were pooled using a random effects model. Relationships between sensitivity and specificity were plotted using summary receiver operator characteristic (sROC) curves. Results All three scores predicted 30 day mortality. The PSI had the highest area under the sROC curve, 0.81 (SE 0.008), compared with CURB65, 0.80 (SE 0.008), p=0.1, and CRB65, 0.79 (0.01), p=0.09. These differences were not statistically significant. Performance characteristics were similar across comparable cut-offs for low, intermediate and high risk for each score. In identifying low risk patients, PSI (groups I and II) had the best negative likelihood ratio 0.08 (0.06-0.12) compared with CURB65 (score 0-1) 0.21 (0.15-0.30) and CRB65 (score 0), 0.15 (0.10-0.22). Conclusion There were no significant differences in overall test performance between PSI, CURB65 and CRB65 for predicting mortality from community-acquired pneumonia.
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PMID: 20729231 [PubMed - as supplied by publisher]4: Eur Respir J. 2010 Aug 20; [Epub ahead of print]
Chalmers JD, Akram AR, Hill AT.
* Royal Infirmary of Edinburgh Edinburgh United Kingdom.
To identify, synthesise and interpret the evidence relating to strategies to increase the proportion of low risk patients with community-acquired pneumonia treated in the community. A systematic review of intervention studies conducted between 1981-2010. Articles were included if they compared strategies to increase outpatient care with usual care. Outcomes were: the proportion of patients treated as outpatients, mortality, hospital readmissions, health related quality of life, return to usual activities and patient satisfaction with care. The main analysis included 6 studies. The interventions in these studies were generally complex, but all involved the use of a severity score to identify low risk patients. Overall, a significantly larger numbers of patients were treated in the community with these interventions: odds ratio(OR) 2.31(95% CI 2.03-2.63). The interventions appear safe, with no significant differences in mortality OR 0.83(0.59-1.17), hospital readmissions OR 1.08(0.82-1.42) or patient satisfaction with care OR 1.21(0.97-1.49) between the intervention and control groups. There was insufficient data regarding quality of life or return to usual activities. All studies had significant limitations. The available evidence suggests that interventions to increase the proportion of patients treated in the community are safe, effective and acceptable to patients.
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PMID: 20729221 [PubMed - as supplied by publisher]5: Chest. 2010 Aug 19; [Epub ahead of print]
Shiloh AL, Savel RH, Paulin LM, Eisen LA.
From the Division of Critical Care Medicine, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA.
Abstract BACKGROUND: Ultrasound-guidance is commonly used for the placement of central venous catheters (CVC). The Agency for Healthcare Research and Quality (AHRQ) recommends the use of ultrasound for CVC placement as 1 of their 11 practices to improve patient care. Despite increased access to portable ultrasound machines and comfort with ultrasound-guided CVC access, fewer clinicians are familiar with ultrasound-guided techniques of arterial catheterization. The goal of this systematic review and meta-analysis was to determine the utility of real-time two-dimensional (2-D) ultrasound-guidance for radial artery catheterization. METHODS: A comprehensive literature search of Medline, Embase, and the Cochrane Central Register of Controlled Trials by two independent reviewers identified prospective, randomized controlled trials (RCT) comparing ultrasound-guidance with traditional palpation techniques of radial artery catheterization. Data were extracted on study design, study size, operator and patient characteristics, and the rate of first-attempt success. A meta-analysis was constructed to analyze the data. RESULTS: Four trials with a total of 311 subjects were included in the review, with 152 subjects included in the palpation group and 159 subjects in the ultrasound-guided group. Compared with the palpation method, ultrasound-guidance for arterial catheterization was associated with a 71% improvement in the likelihood of first-attempt success (relative risk 1.71, 95% confidence interval 1.25-2.32). CONCLUSION: The use of real-time 2-D ultrasound-guidance for radial artery catheterization improved first pass success rate.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20724734&dopt=ExternalLink
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PMID: 20724734 [PubMed - as supplied by publisher]6: Chest. 2010 Aug 12; [Epub ahead of print]
Lam DC, Lui MM, Lam JC, Ong LH, Lam KS, Ip MS.
Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China.
Obstructive sleep apnea (OSA) is associated with disorders of glucose metabolism. Previous studies revealed high prevalence of OSA among type 2 diabetes mellitus (DM) subjects. The aims of this study were to find out the prevalence of OSA and associated clinical factors in Chinese patients with DM. All records of the DM clinic at a teaching hospital in Hong Kong were screened between January 2007 and June 2008. Inclusion criteria were Chinese, age 18-75 years and type 2 DM. Patients with unstable medical illnesses, gestational diabetes or on renal replacement therapy were excluded. Of 3489 records screened, 1859 subjects were eligible. A random sample of 663 (mean age 58.2+/-10.8, mean BMI 26.0+/-4.6), except six with known OSA, were invited for polysomnography(PSG). Of 165 subjects with PSG performed, OSA was diagnosed (Apnea-hypopnea index[AHI] >/= 5.0/hr) in 89 subjects(53.9%, median Epworth Sleepiness Scale: 6 [3,10]). Fifty-four(32.7%) had moderate-severe OSA(AHI>==15/hr). The estimated OSA prevalence in this diabetic cohort was 17.5%(24.7% in men, 10.3% in women). Regression analysis identified that AHI was associated independently with higher BMI, advanced age, male gender and higher diastolic blood pressure(R(2)=29.6%). The adjusted odds ratio of requiring >/= three antihypertensive drugs in moderate/severe OSA was 2.48 (95% CI 1.05 - 5.87). No association with glycemic control(HbA1c) and sleep was identified. In conclusion, OSA is more prevalent in Chinese adults with DM than in the general population. A high index of suspicion for OSA in DM patients is warranted since they may not have overt daytime sleepiness. Trial registration: clinicaltrials.gov; Identifier: NCT00876980.
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PMID: 20705796 [PubMed - as supplied by publisher]7: Eur Respir J. 2010 Aug 6; [Epub ahead of print]
Steinfort DP, Khor YH, Manser RL, Irving LB.
Royal Melbourne Hospital. Parkville 3050 Australia.
Improved diagnostic sensitivity of bronchsocopy for investigation of peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial ultrasound (EBUS) has been reported, though diagnostic performance varies considerably. A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity. Sixteen studies, with 1,420 patients, fulfilled inclusion criteria. Significant inter-study variation in EBUS method was noted. EBUS had point specificity of 1.00 (95%CI 0.99-1.00) and point sensitivity of 0.73 (95%CI 0.70-0.76 for the detection of lung cancer, with a positive likelihood ratio of 26.84 (12.60-57.20) and a negative likelihood ratio of 0.28 (0.23-0.36). Significant inter-study heterogeneity for sensitivity was seen, with prevalence of malignancy, lesion size, and reference standard used being possible sources. EBUS is a safe and relatively accurate tool in investigation of PPLs. Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Further methodologically rigorous studies on well-defined patient populations are required to evaluate the generalisability of our results.
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PMID: 20693253 [PubMed - as supplied by publisher]8: Chest. 2010 Aug 5; [Epub ahead of print]
Rodrigo GJ, Neffen H, Castro-Rodriguez JA.
Departamento de Emergencia, Hospital Central de las Fuerzas Armadas. Montevideo, Uruguay. E-mail: gurodrig@adinet.com.uy.
ABSTRACT BACKGROUND: Omalizumab is a humanized monoclonal anti-IgE for the treatment of severe allergic asthma. Because omalizumab targets an immune system molecule there has been particular interest in the drug's safety. METHODS: To establish the efficacy and safety of subcutaneous omalizumab as add on therapy to corticosteroids, a systematic review of placebo-controlled studies was performed. Primary outcomes were reduction of steroid use and asthma exacerbations. Secondary outcomes measures included lung function, rescue medication use, asthma symptoms, health-related quality of life, and adverse effects. RESULTS: Eight trials (3429 participants) fulfilled the selection criteria. At the end of steroid reduction phase, patients taking omalizumab were more likely to be able to withdraw corticosteroids completely compared with placebo (Relative Risk [RR] = 1.80; 95% CI, 1.42, 2.28, p = 0.00001). Omalizumab patients showed a decreased risk for asthma exacerbations at the end of stable (RR = 0.57, 95% CI: 0.48-0.66, p = 0.0001) and adjustable-steroid phases (RR = 0.55, 95% CI, 0.47, 0.64, p = 0.0001; post-hoc analysis suggests this effect was independent of duration of treatment, age, severity of asthma, and risk of bias. The frequency of serious adverse effects was similar between omalizumab (3.8%) and placebo (5.3%). However, injection site reactions were more frequent in the omalizumab patients (19.9% vs. 13.2%). There were no indications of increased risk of hypersensitivity reactions, cardiovascular effects, and malignant neoplasms. CONCLUSIONS: Data indicate that the efficacy of add on omalizumab in patients with moderate to severe allergic asthma is accompanied by an acceptable safety profile.
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PMID: 20688929 [PubMed - as supplied by publisher]9: Thorax. 2010 Aug;65(8):711-8.
Hoogendoorn M, Feenstra TL, Hoogenveen RT, Rutten-van Molken MP.
Institute for Medical Technology Assessment, Erasmus University, Rotterdam, The Netherlands. hoogendoorn@bmg.eur.nl
BACKGROUND: The aim of this study was to estimate the long-term (cost-) effectiveness of smoking cessation interventions for patients with chronic obstructive pulmonary disease (COPD). METHODS: A systematic review was performed of randomised controlled trials on smoking cessation interventions in patients with COPD reporting 12-month biochemical validated abstinence rates. The different interventions were grouped into four categories: usual care, minimal counselling, intensive counselling and intensive counselling + pharmacotherapy ('pharmacotherapy'). For each category the average 12-month continuous abstinence rate and intervention costs were estimated. A dynamic population model for COPD was used to project the long-term (cost-) effectiveness (25 years) of 1-year implementation of the interventions for 50% of the patients with COPD who smoked compared with usual care. Uncertainty and one-way sensitivity analyses were performed for variations in the calculation of the abstinence rates, the type of projection, intervention costs and discount rates. RESULTS: Nine studies were selected. The average 12-month continuous abstinence rates were estimated to be 1.4% for usual care, 2.6% for minimal counselling, 6.0% for intensive counselling and 12.3% for pharmacotherapy. Compared with usual care, the costs per quality-adjusted life year (QALY) gained for minimal counselling, intensive counselling and pharmacotherapy were euro 16 900, euro 8200 and euro 2400, respectively. The results were most sensitive to variations in the estimation of the abstinence rates and discount rates. CONCLUSION: Compared with usual care, intensive counselling and pharmacotherapy resulted in low costs per QALY gained with ratios comparable to results for smoking cessation in the general population. Compared with intensive counselling, pharmacotherapy was cost saving and dominated the other interventions.
Publication Types: Meta-Analysis Research Support, Non-U.S. Gov't Review
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PMID: 20685746 [PubMed - indexed for MEDLINE]10: Chest. 2010 Jul 29; [Epub ahead of print]
Raad D, Gaddam S, Schunemann HJ, Irani J, Abou Jaoude P, Honeine R, Akl EA.
1Department of Medicine, State University of New York at Buffalo, NY, USA.
Abstract BACKGROUND: While common in many Middle Eastern Countries, waterpipe smoking is increasingly popular in Western cultures. The primary objective of this study was to systematically review the effects of waterpipe tobacco smoking on lung function. The secondary objective was to compare the effects of waterpipe tobacco smoking and cigarette smoking on lung function. METHODS: We conducted a systematic review using the approach of the Cochrane Collaboration to searching for, selecting and abstracting studies. We conducted two separate meta-analyses comparing respectively: (1) waterpipe smokers and non-smokers, and (2) waterpipe smokers and cigarette smokers for each of 3 spirometric measurements (Forced Expiratory Volume in the first second (FEV(1)), Forced Vital Capacity (FVC), and FEV(1)/FVC). We used the standardized mean difference (SMD) to pool the results. RESULTS: Six cross-sectional studies were eligible for this review. Compared with no smoking, waterpipe smoking was associated with a statistically significant reduction in FEV(1) (SMD = -0.43; 95% confidence interval (CI) -0.58, -0.29; equivalent to a 4.04% lower FEV(1)%), and a trend toward lower FVC (SMD = -0.15; 95% CI -0.34, 0.04; equivalent to a 1.38% reduction in FVC%), and FEV(1)/FVC (SMD = -0.46; 95% CI -0.93, 0.01; equivalent to a 3.08% lower FEV(1)/FVC). Comparing waterpipe smoking with cigarette smoking, there was no statistically significant difference in FEV(1), FVC, and FEV(1)/FVC. The six studies suffered from methodological limitations. CONCLUSION: Waterpipe tobacco smoking negatively affects lung function and may be as harmful as cigarette smoking. Waterpipe smoking, therefore, is likely to be a cause of COPD.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20671057&dopt=ExternalLink
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PMID: 20671057 [PubMed - as supplied by publisher]11: Thorax. 2010 Jul;65 Suppl 1:i1-58.
Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group.
Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK. mark.pasteur@nnuh.nhs.uk
The diagnosis, investigation and particularly management of bronchiectasis has been largely empirical and the subject of relatively few controlled clinical trials. There are no clear guidelines, although an Australian position statement has been published concerning bronchiectasis in children. The purposes of these guidelines were therefore threefold: (1) to identify relevant studies in non-cystic fibrosis (CF) bronchiectasis; (2) to provide guidelines on management based on published studies where possible or a consensus view; and (3) to identify gaps in our knowledge and identify areas for future study.
Publication Types: Practice Guideline Review
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PMID: 20627931 [PubMed - indexed for MEDLINE]12: Am J Respir Crit Care Med. 2010 Jul 9; [Epub ahead of print]
Davis SD, Rosenfeld M, Kerby GS, Brumback L, Kloster MH, Acton JD, Colin AA, Conrad CK, Hart MA, Hiatt PW, Mogayzel PJ, Johnson RC, Wilcox SL, Castile RG.
Department of Pediatrics; Division of Pediatric Pulmonology; North Carolina Children's Hospital, University University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
RATIONALE: The conduct of clinical trials in infants with cystic fibrosis (CF) has been hindered by lack of sensitive outcome measures. OBJECTIVES: To evaluate safety, feasibility, and ability to detect abnormalities in lung function of serial pulmonary function tests (PFTs) in infants with CF. METHODS: Multicenter observational study utilizing a commercial device, rigorous training, ongoing quality control, and over-reading of data by an independent panel. Raised volume rapid thoracoabdominal compression technique and plethysmography were performed at enrollment, 6 and 12 months, with an additional 1-month reproducibility visit. MEASUREMENTS AND MAIN RESULTS: 342 procedures were performed in 100 infants with CF at 10 centers. FRC measurements were acceptable at a higher proportion of study visits (89%) than raised volume (72%) or fractional lung volume (68%) measurements. Average z-scores for many parameters differed significantly from historical control values. Mean (95% CI) z scores were -0.52 (-.78, -.25) for forced expiratory flow at 75% of FVC (FEF75); 1.92 (1.39, 2.45) for FRC; 1.22 (0.68, 1.76) for RV; 0.87 (0.60, 1.13) for FRC/TLC and 0.66 (0.27, 1.06) for RV/TLC. For future multicenter clinical trials utilizing infant PFTs as primary endpoints, minimum detectable treatment effects are presented for several sample sizes. CONCLUSIONS: In this 10-center study, key PFT measures were significantly different in CF infants than in historical controls. However, infant PFTs do not yet appear ready as primary efficacy endpoints for multicenter clinical trials, particularly at inexperienced sites, based on acceptability rates, variability, and potentially large sample sizes required to detect reasonable treatment effects.
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PMID: 20622043 [PubMed - as supplied by publisher]13: Eur Respir J. 2010 Jul;36(1):196-201.
Hedlin G, Bush A, Lodrup Carlsen K, Wennergren G, De Benedictis FM, Melen E, Paton J, Wilson N, Carlsen KH; Problematic Severe Asthma in Childhood Initiative group.
Astrid Lindgren Children's Hospital, Q2:05, Karolinska University Hospital, 17176 Stockholm, Sweden. gunilla.hedlin@ki.se
Although most children with asthma are easy to treat with low doses of safe medications, many remain symptomatic despite every therapeutic effort. The nomenclature regarding this group is confusing, and studies are difficult to compare due to the proliferation of terms describing poorly defined clinical entities. In this review of severe asthma in children, the term problematic severe asthma is used to describe children with any combination of chronic symptoms, acute severe exacerbations and persistent airflow limitation despite the prescription of multiple therapies. The approach to problematic severe asthma may vary with the age of the child, but, in general, three steps need to be taken in order to separate difficult-to-treat from severe therapy-resistant asthma. First, confirmation that the problem is really due to asthma requires a complete diagnostic re-evaluation. Secondly, the paediatrician needs to systematically exclude comorbidity, as well as personal or family psychosocial disorders. The third step is to re-evaluate medication adherence, inhaler technique and the child's environment. There is a clear need for a common international approach, since there is currently no uniform agreement regarding how best to approach children with problematic severe asthma. An essential first step is proper attention to basic care.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20595164&dopt=ExternalLink
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PMID: 20595164 [PubMed - in process]14: Eur Respir J. 2010 Jul 1; [Epub ahead of print]
Hoogendoorn M, Hoogenveen RT, Rutten-van Molken MP, Vestbo J, Feenstra TL.
Erasmus University Rotterdam The Netherlands.
Objective of the study was to estimate the case-fatality of a severe exacerbation from long-term survival data presented in the literature. A literature search identified studies reporting at least 1.5 year survival after a severe COPD exacerbation resulting in hospitalization. Each study's survival curve was divided into a critical and a stable period. Mortality during the stable period was then estimated by extrapolating the survival curve during the stable period back to the time of exacerbation onset. Case-fatality was defined as the excess mortality that results from an exacerbation and was calculated as 1 minus the (backwardly) extrapolated survival during the stable period at the time of exacerbation onset. The 95% confidence intervals of the estimated case-fatalities were obtained by bootstrapping. A random effect model was used to combine all estimates into a weighted average with 95%-confidence interval. The meta-analysis based on six studies that fulfilled the inclusion criteria resulted in a weighted average case-fatality rate of 15.6% (95%CI:10.9%-20.3%), ranging from 11.4% to 19.0% for the individual studies. A severe COPD exacerbation requiring hospitalization not only results in higher mortality risks during hospitalization, but also in the time period after discharge and contributes substantially to total COPD mortality.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20595157&dopt=ExternalLink
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PMID: 20595157 [PubMed - as supplied by publisher]15: Eur Respir J. 2010 Jul 1; [Epub ahead of print]
Aubier M, Buhl R, Ekstrom T, Ostinelli J, van Schayck CP, O Selroos, Haughney J.
Assistance Publique Hopitaux de Paris, Inserm U700 Faculte de Medecine Paris Diderot, Paris France.
The aim of this study was to compare two budesonide/formoterol maintenance doses within the budesonide/formoterol maintenance and reliever therapy concept, and to identify possible patient characteristics at baseline which would predict a better response to a higher than standard maintenance dose (NCT00463866). A total of 8424 patients with symptomatic asthma when using an inhaled corticosteroid (ICS) with or without a long-acting beta2-agonist (LABA) were randomised to budesonide/formoterol 160/4.5 mug 1 (1x2) or 2 (2x2) inhalations bid. Patients used the same inhaler as needed for symptom relief. The primary outcome variable was time to first severe asthma exacerbation. In the total study population the time to first severe asthma exacerbation was prolonged by 18% with 2x2 vs 1x2 (hazard ratio 0.82; p=0.03). Lung function (peak expiratory flow) was the only statistically significant predictor for a better response to 2x2. The mean daily ICS doses were 737 and 463 mug in the 2x2 and 1x2 groups, respectively. In a real life setting budesonide/formoterol maintenance and reliever therapy at the 2x2 maintenance dose did prolong time to first severe exacerbation but at a higher medication load. Patients with low lung function benefited most from the higher maintenance dose. Clinical trial registration: NCT00463866.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20595145&dopt=ExternalLink
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PMID: 20595145 [PubMed - as supplied by publisher]16: Thorax. 2010 Aug;65(8):747-52. Epub 2010 Jun 27.
Chapman KR, Barnes NC, Greening AP, Jones PW, Pedersen S.
Asthma and Airway Centre, University Health Network, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada. kchapman@ca.inter.net
The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting beta agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6-12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7-10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20581409&dopt=ExternalLink
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PMID: 20581409 [PubMed - indexed for MEDLINE]17: Eur Respir J. 2010 Jun 18; [Epub ahead of print]
Trillo-Alvarez C, Cartin-Ceba R, Kor DJ, Kojicic M, Kashyap R, Thakur S, Thakur L, Herasevich V, Malinchoc M, Gajic O.
Mayo Clinic College of Medicine Rochester, Minnesota USA.
Early recognition of patients at high risk of acute lung injury (ALI) is critical for successful enrollment of patients in prevention strategies for this devastating syndrome. We aimed to develop and prospectively validate an acute lung injury prediction score in a population-based sample of patients at risk. In a retrospective derivation cohort, predisposing conditions for ALI were identified at the time of hospital admission. The score was calculated based on the results of logistic regression analysis. Prospective validation was performed in an independent cohort of patients at risk identified at the time of hospital admission. In a derivation cohort of 409 patients with ALI risk factors the lung injury prediction score discriminated patients who develop ALI from those who did not with an AUC of 0.84 (95%CI 0.80-0.89; Hosmer Lemeshow, p=0.60). The performance was similar in a prospective validation cohort of 463 patients at risk of ALI (AUC 0.84, 95%CI 0.77-0.91; Hosmer Lemeshow, p=0.88). Acute lung injury prediction score identifies patients at high risk for ALI before ICU admission. If externally validated, this model will serve to define the population of patients at high risk for ALI in whom future mechanistic studies and ALI prevention trials will be conducted.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20562130&dopt=ExternalLink
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PMID: 20562130 [PubMed - as supplied by publisher]18: Am J Respir Crit Care Med. 2010 Jun 10; [Epub ahead of print]
Prevots DR, Shaw PA, Strickland D, Jackson LA, Raebel MA, Blosky MA, Montes de Oca R, Shea YR, Seitz AE, Holland SM, Olivier KN.
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States.
RATIONALE: Single-site clinic-based studies suggest an increasing prevalence of pulmonary nontuberculous mycobacteria (NTM) disease but systematic data are lacking. OBJECTIVES: To describe prevalence and trends for NTM lung disease at four geographically-diverse integrated heathcare delivery systems in the United States. METHODS: We abstracted mycobacterial culture results from electronic laboratory databases and linked to other datasets containing clinical and demographic information. Possible cases were defined as a single positive NTM pulmonary isolate, and definite cases were defined as two positive sputum cultures, or one positive culture from a bronchoalveolar lavage or lung biopsy. Annual prevalence was calculated using US census data; average annual prevalence is presented for 2004-2006. Poisson regression models were used to estimate the annual percent change in prevalence. MEASUREMENTS AND MAIN RESULTS: 28,697 samples from 7940 patients were included in the analysis. Of these, 3988 (50%) were defined as possible cases, and 1865 (47%) of these were defined as definite cases. Average annual (2004-2006) site-specific prevalence ranged from 1.4 to 6.6 per 100,000. Prevalence was 1.l to 1.6 fold higher among women relative to men across sites. The prevalence of NTM lung disease was increasing significantly at the two sites where trends were studied, by 2.6% per year among women and 2.9% per year among men. Among persons aged >60 years, annual prevalence increased from 19.6 / 100,000 during 1994-1996 to 26.7/100,000 during 2004-2006. CONCLUSIONS: The epidemiology of nontuberculous mycobacterial lung disease is changing, with a predominance of women and increasing prevalence at the sites studied.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20538958&dopt=ExternalLink
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PMID: 20538958 [PubMed - as supplied by publisher]19: Thorax. 2010 Jun;65(6):516-22.
Nagel G, Weinmayr G, Kleiner A, Garcia-Marcos L, Strachan DP; ISAAC Phase Two Study Group.
Institute of Epidemiology, Ulm University, Ulm, Germany. gabriele.nagel@uni-ulm.de
BACKGROUND: The increasing prevalence of asthma and allergy might be related to diet, particularly in Western countries. A study was undertaken to assess the association between dietary factors, asthma and allergy in a large international study including objective measurements of atopy. METHODS: Between 1995 and 2005, cross-sectional studies were performed in 29 centres in 20 countries. Parental questionnaires were used to collect information on allergic diseases and exposure factors and data from 50 004 randomly selected schoolchildren (8-12 years, 29 579 with skin prick testing) were analysed. Random effect models for meta-analysis were applied to calculate combined ORs. RESULTS: Fruit intake was associated with a low prevalence of current wheeze in affluent (OR(adj) 0.86, 95% CI 0.73 to 1.02) and non-affluent countries (OR(adj) 0.71, 95% CI 0.57 to 0.88). Consumption of fish in affluent countries (OR(adj) 0.85, 95% CI 0.74 to 0.97) and of cooked green vegetables in non-affluent countries (OR(adj) 0.78, 95% CI 0.65 to 0.95) was associated with a lower prevalence of current wheeze. Overall, more frequent consumption of fruit, vegetables and fish was associated with a lower lifetime prevalence of asthma, whereas high burger consumption was associated with higher lifetime asthma prevalence. None of the food items was associated with allergic sensitisation. Except for fruit juice and fruit consumption, no associations were found with atopic wheeze. Food selection according to the 'Mediterranean diet' was associated with a lower prevalence of current wheeze and asthma ever (p(trend)=0.03). CONCLUSION: Diet is associated with wheeze and asthma but not with allergic sensitisation in children. These results provide further evidence that adherence to the 'Mediterranean diet' may provide some protection against wheeze and asthma in childhood.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20522849&dopt=ExternalLink
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PMID: 20522849 [PubMed - in process]20: Thorax. 2010 Jun;65(6):492-8.
Jordan RE, Lam KB, Cheng KK, Miller MR, Marsh JL, Ayres JG, Fitzmaurice D, Adab P.
Unit of Public Health, Epidemiology & Biostatistics, Public Health Building, University of Birmingham, Edgbaston, Birmingham, UK. r.e.jordan@bham.ac.uk
OBJECTIVES: Case finding is proposed as an important component of the forthcoming English National Clinical Strategy for chronic obstructive pulmonary disease (COPD) because of accepted widespread underdiagnosis worldwide. However the best method of identification is not known. The extent of undiagnosed clinically significant COPD in England is described and the effectiveness of an active compared with an opportunistic approach to case finding is evaluated. METHODS: A cross-sectional analysis was carried out using using Health Survey for England (HSE) 1995-1996 data supplemented with published literature. A model comparing an active approach (mailed questionnaires plus opportunistic identification) with an opportunistic-only approach of case finding among ever smokers aged 40-79 years was evaluated. There were 20 496 participants aged >or=30 years with valid lung function measurements. The main outcome measure was undiagnosed clinically significant COPD (any respiratory symptom with both forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) <0.7 and FEV(1) <80% predicted). RESULTS: 971 (4.7%) had clinically significant COPD, of whom 840 (86.5%) did not report a previous diagnosis. Undiagnosed cases were more likely to be female, and smoked less. 25.3% had severe disease (FEV(1) <50% predicted), 38.5% Medical Research Council (MRC) grade 3 dyspnoea and 44.1% were current smokers. The active case-finding strategy can potentially identify 70% more new cases than opportunistic identification alone (3.8 vs 2.2 per 100 targeted). Treating these new cases could reduce hospitalisations by at least 3300 per year in England and deaths by 2885 over 3 years. CONCLUSIONS: There is important undiagnosed clinically significant COPD in the population, and the addition of a systematic case-finding approach may be more effective in identifying these cases. The cost-effectiveness of this approach needs to be tested empirically in a prospective study.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20522845&dopt=ExternalLink
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PMID: 20522845 [PubMed - in process]