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Medical Journal Review

June 2019

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.

Detection of serum and salivary IgE and IgG1 immunoglobulins specific for diagnosis of food allergy
Nunes MPO, van Tilburg MF, Tranmontina Florean EOP, Guedes MIF
PLoS One 2019; 14(4):e0214745. doi: 10.1371/journal.pone.0214745.
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With the growing prevalence of food allergy, new modalities for diagnostic testing in this disorder are being examined. This study aimed to verify the possible use of saliva for the detection of IgE and IgG1 for the diagnosis of food allergy. To do so, Nunes and colleagues performed a randomized, cross-sectional clinical study with a quantitative approach in a sample of 36 children, ages 1 and 60 months, with a diagnosis of cow’s milk protein allergy (CMPA) by the radioallergosorbent (RAST) test. Serum and saliva samples of the participants were collected and subsequently subjected to the indirect immunoenzymatic assay (ELISA) for the detection of specific serum and salivary immunoglobulins for food: corn, papaya, cow’s milk, egg white, wheat, soybeans, peanuts, nuts, kiwi, cacao, fish, shrimp, bananas and tomatoes.  When serum IgE and IgG1 concentrations were compared, there was no statistical difference (p > 0.05) in 12 of the 14 foods evaluated. The same amount (n = 12) of non-significant differences (p > 0.05) was observed in the comparison of the 14 foods under IgE and IgG1 contractions in saliva. In the verification of the average values of IgE present in the serum and saliva of the foods, only cow’s milk, fish and papaya demonstrated statistically significant differences (p < 0.05). Of the total food evaluated, only the average levels of IgG1 present in serum and saliva showed a significant value (p < 0.05) in banana and tomato. The authors conclude that these findings indicate that the detection of IgE and IgG1 in saliva proves to be as efficient as in the serum, but in truth, this demonstrates sensitivity and not true food allergy. Challenge studies to confirm the diagnosis are needed, as in the end, our desire as clinicians is to find a tool to aid in determining true food allergy.

Paternal tobacco smoke correlated to offspring asthma and prenatal epigenetic programming
Wu C-C, Hsu T-Y, Chang J-C, Ou C-Y, Juo H-C et al.
Frontiers in Genetics 2019;10:471. doi: 10.3389/fgene.2019.00471
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As little is known regarding the effects of paternal tobacco smoke (PTS) on the offspring’s asthma and its prenatal epigenetic programming, Wu et al. investigated whether PTS exposure was associated with the offspring’s asthma and correlated to epigenetic CG methylation of potential tobacco-related immune genes: LMO2, GSTM1 or/and IL-10. They studied a birth cohort of 1,629 newborns, measuring exposure rates of PTS (23%) and maternal tobacco smoke (MTS, 0.2%), cord blood DNA methylation, infant respiratory tract infection, childhood DNA methylation, and childhood allergic diseases, and they found that infants with prenatal PTS exposure had a significantly higher risk of asthma by the age of 6 than those without (p = 0.026). The PTS exposure doses at 0, <20, and ≧20 cigarettes per day were significantly associated with the trend of childhood asthma and the increase of LMO2-E148 (p = 0.006), and IL10_P325 (p = 0.008) CG methylation. Furthermore, the combination of higher CG methylation levels of LMO2_E148, IL10_P325, and GSTM1_P266 corresponded to the highest risk of asthma by 43.48%, compared to other combinations (16.67–23.08%) in the 3-way multi-factor dimensionality reduction (MDR) analysis. The LMO2_P794 and GSTM1_P266 CG methylation levels at age 0 were significantly correlated to those at age of 6. Overall, this indicates that prenatal PTS exposure increases CG methylation contents of immune genes, such as LMO2 and IL-10, which correlates with the development of childhood asthma. This suggests that modulation of the LMO2 and IL-10 CG methylation and/or their gene expression may provide an intervention for early prevention of PTS-associated childhood asthma.

Electronic clinical decision support system (eCDSS) in the management of asthma: from theory to practice
Bousquet J
European Respiratory Journal 2019; 53(4). pii: 1900339. doi: 10.1183/13993003.00339-2019.
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As per guidelines, level of control as well as an asthma action plan should be developed as part of the visit. However, it is difficult and time-consuming to regularly assess control in primary care. mHealth has the potential to transform the face of healthcare and one of its benefits can be to provide a clinical decision support system (CDSS). CDSS is a health information technology system designed to assist clinicians and other health care professionals in clinical decision-making.  In this editorial, Bousquet discusses a recent study reported by GUPTA et al. which compared usual care (year 1) versus a computerized CDSS (the Electronic Asthma Management System; eAMS) (year 2). This study took place in three Canadian primary care sites and included asthmatic adults who had received asthma medication over the past 12 months. The eAMS consisted of a touch tablet patient questionnaire that was completed in the waiting room, resulting in an electronic medical record-integrated clinician decision support. The primary outcome was the delivery of an action plan that increased the number of eligible patients from 0 to 18%. Physician visits with action plan delivery increased by 30.5%. The level of assessment of asthma control increased from 5% to 28%. Clinicians escalated controller therapy in 3.2% of baseline visits versus 126/3240 (3.9%) of intervention visits (p=0.12). At baseline, a short-acting beta-agonist alone was added in 62 visits and a controller was added in 54 visits. With the intervention, this occurred in 33 and 229 visits (p<0.001). Dr. Bousquet notes several limitations regarding this study, including: need to clarify asthma severity in patients using this tool, ensure that eAMS is truly integrated into real world clinical workflow. Despite these concerns, he notes that this study paves the way for the implementation of an eCDSS to improve asthma control.

Lower airway microbiota associates with inflammatory phenotype in severe preschool wheeze
Robinson PFM, Pattaroni C, Cook J, Gregory L, Alonso AM et al.
Journal of Allergy and Clinical Immunology 2019;143(4):1607-1610.e3. doi: 10.1016/j.jaci.2018.12.985.
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In this study, the authors hypothesized that lower airway inflammation and microbial dysbiosis during stable disease in preschool children with recurrent severe wheeze (requiring hospitalization or systemic corticosteroids) would be related to clinical wheeze phenotype. To prove this, they prospectively determined clinical phenotype and analyzed lower airway inflammation and the microbiota in children aged 1 to 6 years with severe wheeze undergoing a clinically indicated bronchoscopy. They found that there was no consistent relationship between lower airway inflammation or infection and clinical preschool wheeze phenotypes, suggesting that use of clinical phenotype alone to guide maintenance therapy to prevent wheeze attacks was not appropriate. Assessment of the lower airway microbiota revealed 2 groups; a Moraxella species dysbiotic microbiota cluster that was associated with airway neutrophilia and a mixed microbiota cluster with a macrophage- and lymphocyte-predominant inflammatory profile. They suggest that antibiotics might be beneficial only for the Moraxella species cluster.

Polycomb repressive complex 2 is a critical mediator of allergic inflammation
Keenan CR, Iannarella N, Granham AL, Brown AC, Kim RY et al
JCI Insight 2019;4(10). pii: 127745. doi: 10.1172/jci.insight.127745.
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Strategies that intervene with the development of immune-mediated diseases are urgently needed, as current treatments mostly focus on alleviating symptoms rather than disease modification. The authors hypothesize that targeting enzymes involved in epigenetic modifications to chromatin represents an alternative strategy that has the potential to perturb the function of the lymphocytes that drive the immune response. In this article, Keenan and colleagues report that 2 major epigenetic silencing pathways are increased after T cell activation. By specific inactivation of these molecules in the T cell compartment in vivo, they demonstrate that the polycomb repressive complex 2 (PRC2) is essential for the generation of allergic responses. Furthermore, they found that that small-molecule inhibition of the PRC2 methyltransferase, enhancer of zeste homolog 2 (Ezh2), reduces allergic inflammation in mice. More is sure to follow in humans.