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Medical Journal Review

March 2018

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.

Biomarkers of treatment efficacy in patients with chronic spontaneous urticaria

Sánchez-Borges M, Capriles-Hulett A, Caballero-Fonseca F, González-Aveledo L
European Annals of Allergy and Clinical Immunology 2018; 50(1): 5-9. doi:10.23822/EurAnnACI.1764-1489.24

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Unfortunately, at present there are no biomarkers useful to predict the course or therapeutic response in patients with chronic spontaneous urticaria (CSU). Thus, the purpose of this paper was to examine the available information on biomarkers that might be applied for the follow-up of the response to guideline recommended therapies for CSU. Through their analysis, the authors found that clinical manifestations associated with poor responses to antihistamines (AHs) were: atopy, asthma, rhinitis / rhinosinusitis, thyroid disease, hypertension, higher disease activity and duration. Laboratory markers of AH resistance included: Complement C5a fraction, Autologous Serum Skin Test (ASST), Basophil Activation Test (BAT), D-dimer and LCN2 adipokine.

Furthermore, Basophil Histamine Release Assay (BHRA), ASST, and basophil CD203c-upregulating activity in the serum correlated with favorable response to omalizumab (OMA), whereas disease duration and severity, BAT, basophil histamine release assay (BHRA), and D-dimer levels were associated with better responses to Cyclosporine A (CyA). Taken together, the literature does provide some promising biomarkers for patient management in CSU and further research is needed to validate these findings.

Histamine as an emergent indoor contaminant: Accumulation and persistence in bed bug infested homes

DeVries ZC, Santangelo RG, Barbarin AM, Schal C
PLOS One 2018; 13(2): e0192462. doi:10.1371/journal.pone.0192462

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Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Interestingly, bed bugs defecate large amounts of histamine as a component of their aggregation pheromone. Thus, in this study the authors examined if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust) and significantly higher than in control homes not infested with bed bugs (mean < 2.5±1.9 μg/100 mg of sieved household dust). Despite the fact that heat treatments eradicated bed bug infestations, it failed to reduce histamine levels, even three months after treatment. The authors conclude that high concentrations, persistence, and proximity to humans during sleep suggest that bed bug-produced histamine may represent an emergent contaminant and could potentially pose a serious health risk in the indoor environment.

Perspectives in allergen immunotherapy: 2017 and beyond

Pfaar O, Bonini S, Cardona V, Demoly P, Jakob T et al
Allergy 2018; 73Suppl 104:5-23. doi: 10.1111/all.13355

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The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT. The first covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. The second focused on the effects of the enactment of European Directive on the availability of allergens for therapy and diagnosis across the European Union, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. This article presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future of immunotherapy.

Tell me about your hay fever: a qualitative investigation of allergic rhinitis management from the perspective of the patient

Cvetkovski B, Kritikos V, Yan K, Bosnic-Anticevich S
NPJ Primary Care Respiratory Medicine 2018; 28(1): 3. doi:10.1038/s41533-018-0071-0

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Allergic rhinitis (AR) is often sub-optimally managed and is responsible for a significant health and economic burden. With the availability of treatments over-the-counter, bypassing the health care professional (HCP), the patient often takes on the role of caregiver. Research on the role of the patient in AR management in the current environment is limited. This study explored the patient perspective of AR management, focusing on sub-optimal management. Patient perspectives of AR management were explored utilizing a qualitative, phenomenological approach. Adults with AR were included in the study and interviewed. Transcripts were analyzed for recurrent themes and emergent concepts. Forty-seven participants with AR were interviewed about their experiences. Patient reports of delayed diagnosis, treatment fatigue and confidence in the ability to manage their AR themselves, heavily influenced their management preferences. Patients also described barriers associated with AR management including financial expense as well as being mistaken for having an infectious disease. Patients described examples of the impact on their quality of life caused by their AR, yet they strongly believed they could manage it themselves. Overall, this belief that AR is a condition that should be entirely self-managed, contributes to its burden and amplifies patients’ separation from HCPs as well as attaining optimal care.

Endogenous and exogenous sex steroid hormones in asthma and allergy in females: A systematic review and meta-analysis

McCleary N, Nwaru B, Nurmatov UB, Critchley H, Scheikh A
Journal of Allergy and Clinical Immunology 2018; Online ahead of print, 2 Jan. doi:10.1016/j.jaci.2017.11.034

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It is well known that asthma and allergy are more common in males than in females during early childhood, but the incidence, severity, and impact on quality of life are greater in postpubertal females than in males. Female sex steroid hormones may partially explain these differences. In 2 previous systematic reviews, early menarche (<12 years) was associated with an increased asthma risk, whereas no significant association was found between menopause and asthma, although subgroup analyses indicated an increased risk in postmenopausal women using hormone replacement therapy.

In this paper, the authors undertook a systematic review investigating the role of endogenous and exogenous hormonal factors in the development and clinical expression of asthma and allergy in females. Through their analysis, the authors found: compared with typical menarche (11-13 years), early menarche (<11 years) was associated with increased risk of new-onset (odds ratio [OR], 1.49; 95% CI, 1.14-1.94) and ever asthma (OR, 1.06; 95% CI, 1.03-1.10), whereas late menarche (>13 years) was associated with increased risk of ever (OR, 1.11; 95% CI, 1.07-1.15), but not new-onset asthma (OR, 1.13;95% CI, 0.82-1.56); compared with regular menstruation, irregular menstruation was associated with increased risk of current asthma (past 12 months) (OR, 1.59; 95% CI, 1.23-2.05), specifically for atopic (OR, 2.57; 95% CI, 1.66-3.98), but not nonatopic asthma (OR, 0.95; 95% CI, 0.54-1.65); compared with premenopause, menopause onset was associated with increased risk of current asthma (OR, 1.25; 95% CI, 1.04-1.51) and current wheeze (OR, 1.16; 95% CI, 1.05-1.30), but not current allergic rhinitis (OR, 0.94; 95% CI, 0.81-1.10); and results for hormonal contraceptives were mixed, with both increased and decreased risks reported, specifically compared with never use, ever HRT use (hazard ratio [HR], 1.37; 95% CI, 1.22-1.54), past use (HR, 1.41; 95% CI, 1.22-1.63), current use (HR, 1.48; 95% CI, 1.22-1.78), and current use of estrogen-only HRT (HR, 1.85; 95% CI, 1.50-2.28) were associated with increased risk of new-onset asthma and current use was also associated with increased risk of current asthma (OR, 1.42; 95% CI, 1.18-1.70), and current wheeze (OR, 1.40; 95% CI, 1.22-1.61), but not current allergic rhinitis (OR, 1.27; 95% CI, 0.97-1.68).

The risk was higher in non-overweight/non-obese and nonsmoking women than in overweight/obese and smoking women, respectively. It should be noted that all of the evaluated studies in this review had moderate-to-high risk. Lastly, the authors stress that mechanistic work is required to elucidate any relationships, as are further longitudinal observational studies with detailed phenotyping of participants.