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The expanding role of biomarkers in the assessment of smoking-related parenchymal lung diseases.

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The expanding role of biomarkers in the assessment of smoking-related parenchymal lung diseases.

Chest. 2012 Oct 1;142(4):1027-34

Authors: Doyle TJ, Pinto-Plata V, Morse D, Celli BR, Rosas IO

Abstract
Recent advances in the field of clinical biomarkers suggest that quantification of serum proteins could play an important role in the diagnosis, classification, prognosis, and treatment response of smoking-related parenchymal lung diseases. COPD and idiopathic pulmonary fibrosis (IPF), two common chronic progressive parenchymal lung diseases, share cigarette smoke exposure as a common dominant risk factor for their development. We have recently shown that COPD and interstitial lung disease may represent distinct outcomes of chronic tobacco use, whereas others have demonstrated that both diseases coexist in some individuals. In this perspective, we examine the potential role of peripheral blood biomarkers in predicting which individuals will develop COPD or IPF, as well as their usefulness in tracking disease progression and exacerbations. Additionally, given the current lack of sensitive and effective metrics to determine an individual's response to treatment, we evaluate the potential role of biomarkers as surrogate markers of clinical outcomes. Finally, we examine the possibility that changes in levels of select protein biomarkers can provide mechanistic insight into the common origins and unique individual susceptibilities that lead to the development of smoking-related parenchymal lung diseases. This discussion is framed by a consideration of the properties of ideal biomarkers for different clinical and research purposes and the best uses for those biomarkers that have already been proposed and investigated.From the Pulmonary and Critical Care Division (Drs Doyle, Pinto-Plata, Morse, Celli, and Rosas), Brigham and Women's Hospital, Harvard Medical School, Boston MA; and Lovelace Respiratory Research Institute (Dr Rosas), Albuquerque NM.Correspondence to: Ivan O. Rosas, MD, Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Thorn 9, Boston, MA 02115; e-mail: irosas@rics.bwh.harvard.eduFinancial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Pinto-Plata has received honoraria as a member of the speakers' bureau from GlaxoSmithKline plc. Dr Celli has received consulting fees from ALTANA, AstraZeneca, Boehringer Ingelheim GmbH, and GlaxoSmithKline plc; speaking fees from ALTANA, AstraZeneca, Boehringer Ingelheim GmbH, and GlaxoSmithKline plc; and grant support from Boehringer Ingelheim GmbH and GlaxoSmithKline plc. Dr Rosas has received consulting fees from Stromedix, Inc/Biogen Idec, Synovex Corporation, and sanofi-aventis U.S. LLC. Drs Doyle and Morse have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.Other contributions: This work was performed at Brigham and Women's Hospital.Funding/Support: This study was funded by the National Institutes of Health [Grant 5T32 HL007633-25 to Dr Doyle, Grant HL107165-01 to Dr Celli, and Grant K23 HL087030 to Dr Rosas] and by the National Heart, Lung and Blood Institutes [Grant R01 HL087122 to Dr Morse].Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

PMID: 23032451 [PubMed - in process]

Pleural Effusions on the Intensive Care Unit; Hidden Morbidity with Therapeutic Potential.

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Despite 50-60% of intensive care patients demonstrating evidence of pleural effusions there has been little emphasis placed on the role of effusions in the aetiology of weaning failure. Critical illness and mechanical ventilation lead to multiple perturbations of the normal physiological processes regulating pleural fluid homeostasis and consequently failure of normal pleural function occurs.

Effusions can lead to deleterious effects on respiratory mechanics and gas exchange, and when extensive may lead to haemodynamic compromise. The widespread availability of bedside ultrasound has not only facilitated earlier detection of pleural effusions but also safer fluid sampling and drainage. In the majority of patients, pleural drainage leads to improvements in lung function with data from spontaneously breathing individuals demonstrating a consistent symptomatic improvement, whilst a meta-analysis in critically ill patients shows an improvement in oxygenation. The effects on respiratory mechanics are less clear, possibly reflecting heterogeneity of underlying pathology. Limited data on clinical outcome from pleural fluid drainage exists, however it appears to be a safe procedure with a low risk of major complications.

The current level of evidence would support a clinical trial to determine whether the systematic detection and drainage of pleural effusions improves clinical outcomes. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

Adrenaline auto-injectors for the treatment of anaphylaxis with and without cardiovascular collapse in the community.

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Adrenaline auto-injectors for the treatment of anaphylaxis with and without cardiovascular collapse in the community.

Cochrane Database Syst Rev. 2012;8:CD008935

Authors: Sheikh A, Simons FE, Barbour V, Worth A

Abstract
BACKGROUND: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may cause death. Adrenaline (epinephrine) auto-injectors are recommended as the initial, potentially life-saving treatment of choice for anaphylaxis in the community, but they are not universally available and have limitations in their use.
OBJECTIVES: To assess the effectiveness of adrenaline (epinephrine) auto-injectors in relieving respiratory, cardiovascular, and other symptoms during episodes of anaphylaxis that occur in the community.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (Ovid SP) (1950 to January 2012), EMBASE (Ovid SP) (1980 to January 2012 ), CINAHL (EBSCO host) (1982 to January 2012 ), AMED (EBSCO host) (1985 to January 2012 ), LILACS, (BIREME) (1980 to January 2012 ), ISI Web of Science (1950 to January 2012 ). We adapted our search terms for other databases. We also searched websites listing on-going trials: the World Health Organization International Clinical Trials Registry Platform, the UK Clinical Research Network Study Portfolio, and the meta Register of Controlled Trials; and contacted pharmaceutical companies who manufacture adrenaline auto-injectors in an attempt to locate unpublished material.
SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing auto-injector administration of adrenaline with any control including no intervention, placebo, or other adrenergic agonists were eligible for inclusion.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed articles for inclusion.
MAIN RESULTS: None of the 1328 studies that were identified satisfied the inclusion criteria.
AUTHORS' CONCLUSIONS: Based on this review, we cannot make any new recommendations on the effectiveness of adrenaline auto-injectors for the treatment of anaphylaxis. Although randomized, double-blind, placebo-controlled clinical trials of high methodological quality are necessary to define the true extent of benefits from the administration of adrenaline in anaphylaxis via an auto-injector, such trials are unlikely to be performed in individuals experiencing anaphylaxis because of ethical concerns associated with randomization to placebo. There is, however, a need to consider trials in which, for example, auto-injectors of different doses of adrenaline and differing devices are compared in order to provide greater clarity on the dose and device of choice. Such trials would be practically challenging to conduct. In the absence of appropriate trials, we recommend that adrenaline administration by auto-injector should still be regarded as the most effective first-line treatment for the management of anaphylaxis in the community. In countries where auto-injectors are not commonly used, it may be possible to conduct trials to compare administration of adrenaline via auto-injector with adrenaline administered by syringe and ampoule, or comparing the effectiveness of two different types of auto-injector.

PMID: 22895980 [PubMed - indexed for MEDLINE]

Allergen Component Testing for Food Allergy: Ready for Prime Time?

Abstract  
Food allergies can cause life-threatening reactions and greatly influence quality of life. Accurate diagnosis of food allergies is important to avoid serious allergic reactions and prevent unnecessary dietary restrictions, but can be difficult. Skin prick testing (SPT) and serum food-specific IgE (sIgE) levels are extremely sensitive testing options, but positive test results to tolerated foods are not uncommon. Allergen component-resolved diagnostics (CRD) have the potential to provide a more accurate assessment in diagnosing food allergies. Recently, a number of studies have demonstrated that CRD may improve the specificity of allergy testing to a variety of foods including peanut, milk, and egg. While it may be a helpful adjunct to current diagnostic testing, CRD is not ready to replace existing methods of allergy testing, as it not as sensitive, is not widely available, and evaluations of component testing for a number of major food allergens are lacking.
  • Content Type Journal Article
  • Category ANAPHYLAXIS AND DRUG ALLERGY (P LIEBERMAN AND S SPECTOR, SECTION EDITORS)
  • Pages 1-6
  • DOI 10.1007/s11882-012-0311-2
  • Authors
    • Jacob D. Kattan, Division of Pediatric Allergy & Immunology and Jaffe Institute for Food Allergy, The Mount Sinai School of Medicine, New York, NY, USA
    • Julie Wang, Division of Pediatric Allergy & Immunology and Jaffe Institute for Food Allergy, The Mount Sinai School of Medicine, New York, NY, USA

The cystic fibrosis airway microbiome

imagePurpose of review: Culture and molecular approaches have established that lower airway infections are polymicrobial. We consider how this new perspective in cystic fibrosis (CF) may affect treatment choices. Recent findings: Standard clinical microbiology of CF infection exacerbations often fails to provide indications of microbial causes that may drive the onset of exacerbation and the anticipated bacteriologic responses to the usual parenteral antibiotics prescribed as treatment. Antimicrobial responses by nonclassical members of the CF airway microbiome may explain why most patients clinically improve. These other organisms contribute to disease either directly as pathogens missed by conventional microbiology or through synergy with conventional pathogens. With these considerations, therapy may best be guided by directed antibiotic therapy to numerically significant isolates. An example is the Streptococcus milleri group, which we now believe to represent new pathogens that profile the exacerbations of infection in the CF lung and that necessitate specific antibiotic therapy to prevent loss of lung function and reduce frequency of exacerbations. Summary: A comprehensive understanding of airway infections offers the potential for improved disease management in CF patients. Accurate quantitative microbiology will be a prerequisite for routine intervention based on the polymicrobial perspective of CF infection exacerbations.

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