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Inhaled glucocorticoids are often highly effective in treating symptoms of asthma exacerbations, however they are ineffective at treating and preventing exacerbations brought on by rhinovirus infection, especially in children.  Glucocorticoids act by binding to glucocorticoid receptors (GR) α which become activated and translocate to the nucleus, leading to the activation of down-stream anti-inflammatory pathways.  Papi et al sought to determine the mechanistic actions of glucocorticoids during rhinovirus infection by studying factors in these anti-inflammatory pathways ( J Allergy Clin Immunol 2013; 132(5): 1075-1085 ). Using a variety of assays and human bronchial epithelial cells, the authors determined that the rhinovirus RV-16 reduces the ability of dexamethasone to inhibit the pro-inflammatory cytokine IL-1β induction of the chemokine CXCL8.  They went on to show that there is an RV-16 dependent impairment of dexamethasone-induced GRα nuclear translocation that is m...

The severity of asthma symptoms is well known to be attenuated by inhaled corticosteroid (ICS) due to their anti-inflammatory effect.  Long-acting β-agonists (LABA) and long acting muscarinic antagonists (LAMA) are current treatment options for patients that do not respond well to low dose ICSs.  Using data from the double-blind, 3-way, crossover National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network’s Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid, Peters et al sought to determine individual and differential responses of asthmatic patients to salmeterol (LABA) and tiotropium (LAMA) when added to an inhaled corticosteroid, as well as predictors of a positive clinical response to the end points FEV₁, morning peak expiratory flow (PEF), and asthma control days (ACDs) ( J Allergy Clin Immunol 2013; 132(5):1068-1074 ) . In the attempt to personalize the bes...

Eosinophils and exhaled Nitric Oxide (NO) levels are prominent features of asthma.  It is known that both exhaled NO and blood eosinophil counts (B-Eos) are markers of local and systemic eosinophil inflammation respectively, and are elevated in patients with the disease. However, little is known about the association of these markers with wheeze and asthma events.  Malinovschi et al [ J Allergy Clin Immunol 2013; 132(4):821-827 ] examined subjects from National Health and Nutrition Examination Survey 2007-2008 and 2009-2010 to determine individual and independent B-Eos and Fraction of Exhaled Nitric Oxide (FENO) levels in relation to wheeze, asthma diagnosis, and asthma events. From the cross sectional study, 12,408 subjects ranging from 6-80 years old were selected who had FENO measurements and blood differential counts.  The authors report that the prevalence of current asthma and wheeze increased progressively with FENO values and B-Eos values.  Furthermore, ther...

The prevalence of asthma is ubiquitous across the United States, but the major allergens of public health relevance that contribute to the disease vary across geographical regions.  Within inner cities, the 2 most common allergens are mouse and cockroach. Ahluwalia et al [ J Allergy Clin Immunol 2013; 132(4):830-835 ] sought to determine the relevant antigen(s) most highly associated with inner city asthma morbidity within Baltimore city. The motivation of their study was not only to aid in the management of asthma within the community but to assist in the reduction of levels of these antigens community wide.  The authors selected 144 children between 7 and 10 years old that had been clinically identified with asthma at least one year before the start of the study.  At the start of the study, they underwent skin prick tests and had clinical data collected at baseline and again at 3, 6, 9, and 12 months.  At the same time points, settled house dust samples were collec...

Keeping on the topic of natural killer cells, Jordan Orange, MD, PhD contributes a review on immunodeficiencies associated with NK cell dysfunction [ J Allergy Clin Immunol 2013; 132(3):515-525 ].  The author provides a concise review of NK cell biology, covering their intrinsic activities of cytotoxicity, tumor surveillance, and co-stimulation and signaling.  Orange points out that NK cell deficiency [NKD] is a subset of primary immunodeficiency diseases [PID] that is difficult to diagnose and treat because of the limited clinical information and testing available.  Like other PID, the author notes that NKD patients are characterized by a susceptibility to chronic and/or severe viral infections, especially herpes viruses.  Accurate diagnosis hinges on determining that the seminal deficiency is associated with NK cells, and that NKD is not secondary to other causes. The author provides an algorithm for identifying primary NKD.  Orange discusses the current class...

This month, Deniz et al. give an overview of current knowledge about natural killer cells [NK cells] and their interface with pathways and mechanisms of adaptive immunity, with attention to allergic disease processes [ J Allergy Clin Immunol 2013; 132(3):527-535 ].  The authors cover fundamentals of NK biology, such as their surface marker characterization, IFN-γ secretion, MHC class I interactions, phenotypes, tissue prevalence, cytokine profiles, and cytotoxicity to target cells.  NK cells are characterized by their cytotoxic activity through release of perforin and granzymes that are targeted at tumor cells, virally infected cells, and IgG antibody expressing cells, cytokine and chemokine secretion and signaling of adaptive immune cells, and co-stimulatory interaction with antigen presenting cells [APC] via IL-10 and TGF-β.   Deniz et al. note that NK chemokine secretion is particularly important in the co-localization and mutual maturation of dendritic cells [DC]...

In a review this month, Greer and co-authors present interesting information on just how much our health depends on the well-being and communal balance of the microscopic symbionts in our gastrointestinal tract [ Journal of Allergy and Clinical Immunology 2013; 132(2): 253-262 ].  They begin their review noting that, until fairly recently, immunity, metabolic functions and gut physiology had been studied as separate biological systems.  In light of growing evidence that the delineation between these is arbitrary, the authors point out that systems biology has developed new methods for investigating the interactions between the intestinal microbiota and immune and metabolic outcomes. Greer et al covers two broad categories, small intestine enteropathies and obesity with metabolic syndrome.  They describe current animal models used to study immunodeficiency enteropathies, celiac disease, inflammatory bowel disease, obesity and lipid metabolism dysregulation. The authors di...