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Medical Journal Review

October 2017

WAO Reviews – Editors' Choice

The Editors select articles for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases, and whenever possible they seek articles that everyone can access freely. The Editors’ Choice comes to you from Juan Carlos Ivancevich, MD, WAO Web Managing Editor, and summary author, John J. Oppenheimer, MD, FACAAI, FAAAAI, WAO Reviews Editor.

After asthma: redefining airways disease
Pavord ID, Beasley R, Agusti A, Anderson GP, Bel E et al
The Lancet Commissions 2017; Online ahead of print (September 11)  (DOI: 10.1016/S0140-6736(17)30879-6


In this “Lancet Commission”, a group of experts provides a view of where we are and where we need to go in attempt to resolve the public health problem of asthma. As the authors note, this article is not intended as a comprehensive review but the collective view and opinions of the international expert panel. It is truly an amazing document that begins with the historical landmarks regarding our present understanding of asthma, stressing the utility of phenotypic discriminators in the treatment of asthma (with attention to biologic therapies) as well as future directions regarding asthma research.

Comparison of the performance of Skin Prick, ImmunoCAP, and ISAC tests in the diagnosis of patients with allergy
Griffiths RLM, El-Shanawany T, Jolles SRA, Selwood C, Heaps AG et al
International Archives of Allergy and Immunology 2017; 172(4): 215-223 (DOI: 10.1159/000464326)


In this study by Griffiths et al., the authors retrospectively analyzed the medical records of 118 patients attending the National Adult Allergy Service at the University Hospital of Wales who presented diagnostic difficulty, to evaluate which testing strategy (SPT, ImmunoCAP, or ISAC) was the most effective in confirming the diagnosis in this “complex” population. They found that in patients with nut allergy, the detection rates of SPTs (56%) and ISAC (65%) were lower than those of ImmunoCAP (71%). ISAC had a higher detection rate (88%) than ImmunoCAP (69%) or SPT (33%) in the diagnosis of oral allergy syndrome. ImmunoCAP test results identified all 9 patients with anaphylaxis due to wheat allergy (100%), whereas ISAC was positive in only 6 of these 9 (67%). One must, however, note the potential limitations of this study, including the small number of patients when considering specific allergens, as well as the fact that challenges were not performed and thus the outcome of allergy is based upon history.

Molecular aspects of allergens in atopic dermatitis
Camapana R, Dzoro S, Mittermann I, Fedenko E, Elisyutina O et al.
Current Opinion in Allergy and Clinical Immunology 2017; 17(4): 269-277  (DOI: 10.1097/ACI. 0000000000000378)


In this review, Campana and colleagues explored the literature regarding molecular aspects of allergens in atopic dermatitis. They show that recombinant allergens and allergen derivatives are helpful in dissecting the “pathomechanisms” of atopic dermatitis. Specifically, molecular testing with defined allergen molecules is useful in the diagnostic management of patients with atopic dermatitis to guide new forms of personalized treatment. Furthermore, molecular allergology is helpful in the selection of patients with atopic dermatitis for IgE-targeting and T cells-targeting strategies, for allergen avoidance and allergen-specific immunotherapy (AIT). In the future, innovative allergy vaccines based on recombinant allergen derivatives will likely be useful for treatment of patients with atopic dermatitis.

Bacterial ᴅ-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells
Lee RJ, Hariri BM, McMahon DB, Chen B, Doghramji L et al
Science Signaling 2017; 10(495): eaam 1703  (DOI: 10.1126/scisignal.aam7703)


It has been shown in the past that in the upper respiratory epithelium, bitter and sweet taste receptors (present in solitary chemosensory cells) can influence antimicrobial innate immune defense responses. Activation of bitter taste receptors (T2Rs) stimulates surrounding epithelial cells to release antimicrobial peptides, while activation of the sweet taste receptor (T1R) in the same cells inhibits this response. The authors hypothesized that ᴅ-amino acids, which are produced by various bacteria and activate T1R in taste receptor cells in the mouth, may also activate T1R in the airway. In this study, they demonstrated that both the T1R2 and T1R3 subunits of the sweet taste receptor (T1R2/3) were present in the same chemosensory cells of primary human sinonasal epithelial cultures. Furthermore, respiratory isolates of Staphylococcus species, but not Pseudomonas aeruginosa, produced at least two ᴅ-amino acids that activate the sweet taste receptor. In addition to inhibiting P. aeruginosa biofilm formation, ᴅ-amino acids derived from Staphylococcus inhibited T2R-mediated signaling and defensin secretion in sinonasal cells by activating T1R2/3. ᴅ-Amino acid–mediated activation of T1R2/3 also enhanced epithelial cell death during challenge with Staphylococcus aureus in the presence of the bitter receptor-activating compound denatonium benzoate. These data establish a potential mechanism for interkingdom signaling in the airway mediated by bacterial ᴅ-amino acids and the mammalian sweet taste receptor in airway chemosensory cells.

Neoneural regulation of type 2 innate lymphoid cells via neuromedin U
Cardoso V, Chesné J, Ribeiro H, García-Cassani B, Carvalho T et al.
Nature 2017; 549(7671): 277-281   (DOI: 10.1038/nature23469)


Previous studies demonstrated that Group 2 innate lymphoid cells (ILC2s) contribute to multiple homeostatic processes, including nutrient sensing, metabolism, and tissue repair as well as infection control. Discrete subsets of immune cells integrate nervous system cues, but it was not known whether neuron-derived signals control ILC2s. In this letter, Cardoso and colleagues demonstrate that neuromedin U (NMU) in mice, which is a fast and potent regulator of type 2 innate immunity in the context of a functional neuron-ILC2 unit, is the molecular link between neuronal sensing, innate type 2 responses and mucosal protection. The authors suggest that coupling neuronal activity and ILC2-dependent immune regulation may have ensured potent, efficient and integrated multi-tissue responses to environmental challenges throughout evolution. Supporting this is the fact that NMU is highly conserved across mammalian, amphibian, avian and fish species. Overall, this and other studies on this topic indicate that the mucosal nervous system partners with immune cells to ensure local tissue regulation, thus indicating that neuroimmune sensory units regulate physiology and homeostasis at an organismic level.