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Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis.

Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis.

Respirology. 2012 Jan 18;

Authors: Homma S, Azuma A, Taniguchi H, Ogura T, Mochiduki Y, Sugiyama Y, Nakata K, Yoshimura K, Takeuchi M, Kudoh S,

Abstract
SUMMARY AT A GLANCE -: A multi-centre, prospective, randomized, controlled trial was conducted to assess the efficacy of monotherapy with inhaled N-acetylcysteine (NAC) in patients with IPF. Exploratory analyses demonstrated that NAC monotherapy stabilized the serial decline in FVC in some patients, without the use of immunosuppressive or anti-fibrotic agents Background and objective: :  Idiopathic pulmonary fibrosis (IPF) is a fatal disorder, for which there are currently no specific or effective medical treatments. A multi-centre, prospective, randomized, controlled clinical trial was conducted to assess the efficacy of inhaled N-acetylcysteine (NAC) monotherapy in Japanese patients with early stage IPF Methods::  Eligible patients had well-defined IPF of mild to moderate severity, with no desaturation on exercise. Of 100 patients screened, 76 were randomly assigned to an NAC treatment group (Group A; n= 38) that received 352.4 mg of NAC by inhalation twice daily. or to a control group (Group B; n= 38) that received no therapy. The primary endpoint was the change from baseline in FVC at 48 weeks. Results::  There were no significant overall differences in the change in FVC between Groups A and B. Post hoc exploratory analyses showed that NAC therapy was associated with stability of FVC in a) a subset of patients with initial FVC <95% of predicted (n= 49; difference in FVC decline 0.12 L; P= 0.02), and b) in patients with initial DLco <55% of predicted (n= 21; difference in FVC decline 0.17 L; P= 0.009). Conclusions::  These findings indicate that NAC monotherapy may have some beneficial effect in patients with early stage IPF. Further trials, in more select IPF populations with progressive disease, are required to prove the efficacy of inhaled NAC. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

PMID: 22257422 [PubMed - as supplied by publisher]

Omalizumab beyond asthma.

Omalizumab beyond asthma.

Allergol Immunopathol (Madr). 2012 Jan 18;

Authors: Sanchez J, Ramirez R, Diez S, Sus S, Echenique A, Olivarez M, Cardona R

Abstract
INTRODUCTION: Omalizumab has been demonstrated to be a successful therapy in the management of asthma through reduction of patient's symptoms and use of inhaled corticosteroids. The effect of omalizumab is achieved by immunoglobulin E (IgE) blockage and other secondary mechanisms resulting from this blockage. Because other diseases have an important IgE mediation in their physiopathology, the question arises as to if omalizumab would be useful in the treatment of other IgE-mediated diseases. OBJECTIVE: We present an overview of the experimental studies and clinical reports evaluating the use of omalizumab in diseases different to asthma including atopic dermatitis, urticaria, eosinophilic gastrointestinal disorders, idiopathic anaphylaxis, latex allergy, hymenoptera venom allergy, and other IgE diseases. METHODS: We reviewed the literature using PUBMED, EMBASE, and LILACS for publications which used omalizumab in the treatment of patients with allergic diseases or any other diseases. Complete articles published in English, Spanish or Portuguese were included. CONCLUSION: There is not enough evidence to support the regular use of omalizumab in IgE diseases other than asthma. However, some experimental and clinical investigations indicate that omalizumab could be a therapeutic option in several allergic diseases like atopic dermatitis, urticaria, and eosinophilic gastrointestinal disorders. More control studies are needed in each IgE disease to evaluate the efficacy and safety of omalizumab in IgE mediated diseases.

PMID: 22264640 [PubMed - as supplied by publisher]

The regulation of fibrosis in airway remodeling in asthma.

The regulation of fibrosis in airway remodeling in asthma.

Mol Cell Endocrinol. 2012 Jan 14;

Authors: Royce SG, Cheng V, Samuel CS, Tang ML

Abstract
Fibrosis is one of the key pathological features of airway remodeling in asthma. In the normal airway the amount of collagen and other extracellular matrix components is kept in equilibrium by regulation of synthesis and degradation. In asthma this homeostasis is disrupted due to genetic and environmental factors. In the airways of patients with the disease there is increased extracellular matrix deposition, particularly in the reticular basement membrane region, lamina propria and submucosa. Fibrosis is important as it can occur early in the pathogenesis of asthma, be associated with severity and resistant to therapy. In this review we will discuss current knowledge of relaxin and other key regulators of fibrosis in the airway including TGFβ, Smad2/3 and matrix metalloproteinases. As fibrosis is not directly targeted or effectively treated by current asthma drugs including corticosteroids, characterization of airway fibrosis and how it is regulated will be essential for the development of novel therapies for asthma.

PMID: 22266540 [PubMed - as supplied by publisher]

Psychosocial stress and asthma morbidity.

Psychosocial stress and asthma morbidity.

Curr Opin Allergy Clin Immunol. 2012 Jan 19;

Authors: Yonas MA, Lange NE, Celedón JC

Abstract
PURPOSE OF REVIEW: The objective of this review is to provide an overview and discussion of recent epidemiologic and mechanistic studies of stress in relation to asthma incidence and morbidity. RECENT FINDINGS: Recent findings suggest that stress, whether at the individual (i.e. epigenetics, perceived stress), family (i.e. prenatal maternal stress, early-life exposure, or intimate partner violence) or community (i.e. neighborhood violence; neighborhood disadvantage) level, influences asthma and asthma morbidity. Key recent findings regarding how psychosocial stress may influence asthma through Posttraumatic Stress Disorder, prenatal and postnatal maternal/caregiver stress, and community violence and deprivation are highlighted. SUMMARY: New research illustrates the need to further examine, characterize, and address the influence of social and environmental factors (i.e. psychological stress) on asthma. Further, research and innovative methodologies are needed to characterize the relationship and pathways associated with stress at multiple levels to more fully understand and address asthma morbidity, and to design potential interventions, especially to address persistent disparities in asthma in ethnic minorities and economically disadvantaged communities.

PMID: 22266773 [PubMed - as supplied by publisher]

Basophil Activation Test in Allergy: Time for an Update?

A wide range of reported evidence in the literature has shown that the quantification of basophil activation by flow cytometry (basophil activation test, BAT) has proven to be a useful tool for the assessment of immediate-type responses to allergens mediated by IgE or other mechanisms in allergic patients. The usefulness of BAT in anaphylactic adverse reactions, late-onset allergy and immunotherapy follow-up has also been demonstrated.

To date, most BAT studies reported in the literature involved the capture of basophils only with a fluorochrome-labeled anti-IgE antibody and application of CD63 upregulation in order to evaluate the basophil response to allergens. Many issues need to be addressed, such as optimizing the analytical performance of the test, checking preanalytical conditions, the selection of the flow cytometry best gating protocol, the introduction of new algorithms and parameters, the search for new activation markers and the introduction of anti-IgE controls.

BAT is certainly a useful technique, also for isolated cases of hypersensitivity to various other compounds and drugs, and an update of its application is certainly an interesting topic to expand the debate on allergy diagnosis.

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