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Medical Journal Review

August 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.

A phenotypically and functionally distinct human TH2 cell subpopulation is associated with allergic disorders.
Wambre E, Bajzik V, DeLong JH, O’Brien K, Nguyen Q-A et al.
Science Translational Medicine 2017; 9(401): eaam9171. DOI: 10.1126/scitranslmed.aam9171


It is well known that allergen-specific type 2 helper T (TH2) cells play a central role in orchestrating the allergic and asthmatic inflammatory response. At present, a major factor limiting the use of such atopic disease causing T cells as a clinical target or biomarker is the lack of an accepted methodology to identify and differentiate these cells from overall nonpathogenic TH2 cell types. In this paper by Wambre and colleagues, the authors have identified a subset of human memory TH2 cells that are specific to atopic individuals. These cells are terminally differentiated CD4+ T cells (CD27− and CD45RB−) characterized by coexpression of CRTH2, CD49d, and CD161 and exhibit numerous functional attributes distinct from conventional TH2 cells. These cells, which the authors suggest be denoted as TH2A cell subset, demonstrate a distinct pathway in the initiation of pathogenic responses to allergen, and elimination of these cells is indicative of clinical responses induced by immunotherapy. The authors conclude that these TH2A cells identify a human TH2 cell signature in allergic diseases that could be used for response-monitoring and designing appropriate immunomodulatory strategies.

Diagnosing allergic sensitizations in the third millennium: why clinicians should know allergen molecular structures.
Alessandri C, Ferrara R, Bernardi ML, Zennaro D, Tuppo L et al.
Clinical and Translational Allergy 2017; 7:21. DOI: 10.1186/s13601-017-0158-7


This is an interesting review of the use of molecular allergology in the quest for personalized medicine. The authors reinforce the fact that not every patient has the same allergic profile, even when they are allergic to the same allergenic source – thus demonstrating that “one size does not fit all”.  Detailed study of the structure–function relationships in allergenic molecules can reveal the structural determinants involved in the IgE-binding. The authors suggest that through improved knowledge of the epitope profile of each allergen and of the environmental/experimental conditions affecting the exposure of IgE binding epitopes we will better understand the cross-reaction processes which will lead to improvement in the implementation of immunotherapy, with the ultimate hope of improved patient outcomes.

Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers’ children against airway inflammation and colitis
Frei R, Ferstl R, Roduit C, Ziegler M, Schiavi E et al.
Journal of Allergy and Clinical Immunology 2017; Article in press (June 2017). DOI:10.1016/j.jaci.2017.04.051


Previous studies have demonstrated that exposure to a farm environment provides protection against the development of inflammatory diseases such as allergy and asthma. This has spurred the hygiene hypothesis which suggests that children growing up in the farm environment are protected from development of atopic disease secondary to an atmosphere rich in microbes and/or microbial components. In this study Frei and colleagues examined the impact of structures of non-microbial origin such as the sialic acid N-Glycolylneuraminic acid [(Neu5Gc) a sialic acid specifically expressed on non-human mammalian cells and glycoproteins and is not present in bacteria]. To do so, they evaluated the anti-Neu5Gc antibody levels in the sera of children enrolled in two farm studies: the PARSIFAL study (n=299) and the PASTURE birth cohort (cord blood (n=836), 1 year (n=734), 4.5 years (n=700) and 6 years (n=728)) and the association of asthma and wheeze. They found that in children, anti-Neu5Gc IgG levels positively correlated with living on a farm and increased peripheral blood Foxp3 expression and inversely correlated with wheezing and asthma in non-atopic subjects. To elucidate the potential mechanism of protection, they utilized a mouse model and found that exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Specifically, they found that Neu5Gc exposure reduced IL-17 positive T cells and supported differentiation of regulatory T cells.

A focus on chronic rhinosinusitis with nasal polyposis: Leaving aside endoscopic surgery, a step towards biologic therapies
Malvezzi L, Ferrando M, Puggioni F, Heffler E, Passalacqua G, Canonica GW
Journal of Otolaryngology–ENT Research 2017; 7(2): 00199. DOI:10.15406/joentr.2017.07.00199


Present traditional surgical treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) has a high recurrence rate. In this paper Malvezzi and colleagues provide a review of the surgical treatments for chronic rhinosinusitis with/without nasal polyps and describe the first applications of biological therapies. The authors stress the current high costs of these agents and encourage research be undertaken to define the distinct subset(s) of CRSwNP patients most likely to respond to biologic tools in attempt to optimize utilization.

Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study.
Murray C, Foden P, Lowe L, Durrington H, Custovic A, Simpson A.
The Lancet Child & Adolescent Health 2017; Article in press (available online 12 July). DOI:10.1016/S2352-4642(17)30008-1


There have been recent concerns that asthma is being over-diagnosed. Thus, the UK National Institute of Health and Care Excellence (NICE) proposed a new diagnostic algorithm applying four lung function measures sequentially (ratio of forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] <70%, bronchodilator reversibility ≥12%, fractional exhaled nitric oxide [FENO] ≥35 parts per billion, and peak expiratory flow variability >20%) to make the diagnosis. In this study, Murray and colleagues assessed the diagnostic value of three of the tests individually, and then tested the proposed algorithm in symptomatic children by utilizing 13–16 year olds from the Manchester Asthma and Allergy Study (MAA study). The authors specifically examined study participants reporting symptoms of wheeze, cough, or breathlessness in the previous 12 months, who were not on regular inhaled corticosteroids in attempt to simulate the primary care environment.

Among the 630 children who completed spirometry in the MAA study, FEV1:FVC was less than 70% in ten (2%) children, of whom only two (20%) had current asthma. Bronchodilator reversibility was positive in 54 (9%) of 624 children, of whom only 12 (22%) had current asthma. FENO was 35 or more parts per billion in 115 (24%) of 485 children, of whom 29 (25%) had current asthma. Only four of 56 children with current asthma had positive results for all three tests (spirometry, bronchodilator reversibility, and FENO). On the other hand, 24 (43%) of the 56 children with current asthma were negative on all three tests. FEV1:FVC (p=0·0075) and FENO (p<0·0001), but not bronchodilator reversibility (p=0·97), were independently associated with asthma in multivariable logistic regression models. Overall indicating that among children who reported recent symptoms, the diagnostic accuracy of the algorithm was poor. The authors conclude that until better evidence is available, the proposed NICE algorithm on asthma diagnosis should not be implemented in children.