Current opinion in allergy and clinical immunology
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Th17 lymphocytes are now widely believed to be critical for the regulation of various chronic immune diseases, including asthma and chronic obstructive pulmonary disease. In this review, we discuss the current understanding of the role of Th17 cells in the pathogenesis of different asthma phenotypes and chronic obstructive pulmonary disease. ⋯ Steroid resistant severe asthma with predominant bronchial neutrophilic inflammation could benefit from IL-17 targeted therapies. In this view, the definition of clinical phenotypes and inflammatory endotypes of asthma in each patient will be necessary for personalizing the therapeutic approach.
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There is considerable evidence that implicates eosinophils as important effector cells in the inflammation characteristic of eosinophilic asthma. IL-5 is central to eosinophil maturation and release from the bone marrow, their subsequent accumulation, activation and persistence in the tissues. IL-5 therefore represents an attractive target to prevent or blunt eosinophil-mediated inflammation resulting in the development of humanized anti-IL-5 monoclonal antibody such as mepolizumab. This review is an update of the evidence demonstrating the effectiveness of mepolizumab treatment of patients with asthma. ⋯ Mepolizumab is a potentially important and well tolerated therapy in carefully selected populations of patients with asthma.
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Curr Opin Allergy Clin Immunol · Apr 2015
ReviewAirway molecular endotypes of asthma: dissecting the heterogeneity.
This review will cover advances over the past year in defining airway endotypes in asthma by gene expression and the relationship between these endotypes and clinical traits. ⋯ Molecular endotyping of asthmatic patients using gene expression profiling of airway samples is helping to uncover disease mechanisms and potential novel treatment targets. The advancement of endotyping methods holds the promise of future personalized treatment for asthma.
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Curr Opin Allergy Clin Immunol · Apr 2015
ReviewChildhood asthma and chronic obstructive pulmonary disease: outcomes until the age of 50.
There has been recent interest in understanding the origins of chronic obstructive pulmonary disease. Epidemiological studies suggest that chronic obstructive pulmonary disease clearly has other causes apart from tobacco smoke. ⋯ Children with severe asthma are at increased risk of developing chronic obstructive pulmonary disease.
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GATA2 deficiency is a germline disease that causes a wide spectrum of phenotypes including viral and bacterial infections, cytopenias, myelodysplasia, myeloid leukemias, pulmonary alveolar proteinosis and lymphedema. The age of clinical presentation ranges from early childhood to late adulthood, with most occurring in adolescence to early adulthood. We review the expanding GATA2-deficient phenotype, molecular genetics of disease and developments in treatment. ⋯ GATA2 is a zinc finger transcription factor essential for embryonic and definitive hematopoiesis as well as lymphatic angiogenesis. GATA2 deficiency is caused by a variety of mutations in the GATA2 gene and can have variable presentation, onset and outcome. Patients are susceptible to mycobacterial, viral and fungal infections and can develop myelodysplasia, acute or chronic leukemias, lymphedema and pulmonary alveolar proteinosis. Hematopoietic stem cell transplantation reverses most of the clinical phenotype with good long-term outcomes.