ADAM Metallopeptidase Domain 33 (ADAM33): A Promising Target for Asthma.

Mediators Inflamm. 2014;2014:572025

Authors: Tripathi P, Awasthi S, Gao P

Abstract
Over the last few years, a significant progress has been made in understanding the role of a disintegrin and metalloproteinase 33 (ADAM33) in asthma. The previous observations for the association with asthma have been replicated in over 33 different population samples worldwide. We and others have performed association analysis and meta-analysis and provided further evidence that several polymorphisms in the ADAM33 are risk factors for asthma, especially in the Asian population. Further, several studies have suggested that alterations in epigenetic marks alter the patterns of DNA methylation of ADAM33 and result in potentially adverse biological effects. Finally, while the biological activities of ADAM33 are as yet unknown, ADAM33 may play a possible role in airway remodeling because of its high expression in epithelium, myo/fibroblasts, and airway smooth muscle cells (ASMCs) and its role in promoting angiogenesis and stimulating cell proliferation and differentiation. Thus, ADAM33 represents a promising target for asthma. However, further investigations are clearly needed to discover functional ADAM33 gene polymorphisms and the role of genetic/epigenetic factors in conferring genetic susceptibility to environmental exposure induced asthma as well as biological function in asthma. This, in turn, will unlock the possibility of ADAM33 as a target for asthma therapy.

PMID: 24817794 [PubMed - as supplied by publisher]

Leukotriene receptor antagonists for chronic urticaria: a systematic review.

Allergy Asthma Clin Immunol. 2014;10(1):24

Authors: de Silva NL, Damayanthi H, Rajapakse AC, Rodrigo C, Rajapakse S

Abstract
A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines. Leukotreine receptor antagonists (LTRA) are also used for chronic urticaria, although firm recommendations on their use are lacking. We performed a systematic review of randomised trials to determine the role of LTRA in treatment of chronic urticaria. A search of PUBMED, EMBASE, SCOPUS, LILACS, the Cochrane Central Register of Controlled Trials, and the Web of Science for relevant randomized control trials or cross over studies yielded 10 eligible studies. The heterogeneity of trials were high, preventing valid meta-analysis of data. Most trials indicated that LTRA are not superior to placebo or antihistamine therapy, while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone. The side effect profile and tolerability of this group of drugs is acceptable. The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well designed randomized controlled trials with clear and standardized outcome measures are needed to determine the role of LTRA in chronic urticaria.

PMID: 24817895 [PubMed - as supplied by publisher]

Related Articles

The clinical implications of integrating additional prognostic factors into the TNM.

J Surg Oncol. 2014 Apr;109(5):391-4

Authors: Henson DE, Schwartz AM, Chen D, Wu D

Abstract
BACKGROUND AND OBJECTIVES: The management of solid tumors is governed by host and tumor factors that traditionally have incorporated TNM staging with additional pathologic, biologic, and clinical host factors. Beyond the anatomic-based TNM, increasingly new prognostic and predictive factors are being discovered that have important survival and treatment implications. However, because the TNM is based on a "bin" model, additional prognostic factors would rapidly overwhelm the current system. This communication demonstrates the clinical implications and improved patient prognosis derived from a new algorithmic model based on clustering analysis.
METHODS: A new algorithm is described that integrates additional factors into the TNM and calculates survival.
RESULTS: The results indicate that additional factors can be integrated into the TNM staging system providing additional patient stratification without changing the TNM definitions. Adding prognostic factors to traditional TNM staging increases substratification of given stages and identifies and separates favorable and unfavorable clinical outcomes for specific TNM stages.
CONCLUSION: Integration of additional prognostic factors into the TNM by a clustering algorithm can change the stratification of patient outcome. This may guide the clinician to select a more rational management program based on the additional factors and improve cohort selection for clinical trials.

PMID: 24338494 [PubMed - indexed for MEDLINE]

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Diagnosis and classification of idiopathic pulmonary fibrosis.

Autoimmun Rev. 2014 Apr-May;13(4-5):508-12

Authors: Kekevian A, Gershwin ME, Chang C

Abstract
Idiopathic pulmonary fibrosis is a difficult disease to diagnose. Idiopathic pulmonary fibrosis is a member of a class of diseases known as idiopathic interstitial pneumonias. Other members include nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and lymphocytic interstitial pneumonia. Usual interstitial pneumonia (UIP) is the pathological equivalent of idiopathic pulmonary fibrosis. Prior to 2011, the diagnosis was based on major and minor criteria, but because these criteria were not evidence based, the criteria were modified by consensus from the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association. These new criteria now include satisfying three core requirements, including exclusion of other possible cause of interstitial lung disease, specific findings of usual interstitial pneumonia on high resolution computed tomography, and a combination of "possible UIP" findings on high resolution computed tomography and UIP findings on lung biopsy. Idiopathic pulmonary fibrosis is a severe, progressive disease with limited treatment options, and exacerbations are associated with a high degree of morbidity and mortality.

PMID: 24424167 [PubMed - indexed for MEDLINE]