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Medical Journal Review

April 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.

Elevated serum OX40L is a biomarker for identifying corticosteroid resistance in pediatric asthmatic patients
Ma SL, Zhang L
BMC Pulmonary Medicine 2019;19(1):66. doi: 10.1186/s12890-019-0819-5
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Recent research in asthma care has been directed toward phenotypes. One such focus has been regarding response to therapy, specifically to corticosteroids. This study aims to evaluate the serum OX40 ligand (OX40L) in pediatric asthmatic patients and to investigate its correlations with clinical characteristics and corticosteroid response. In this study, 192 pediatric asthmatic patients requiring inhaled corticosteroid (ICS) therapy, and 130 healthy controls, were examined. Clinical data were collected, including serum levels of immunoglobulin (IgE), interleukin-6 (IL-6), thymic stromal lymphopoietin (TSLP), and OX40L. The level of serum OX40L was compared between the steroid-sensitive asthma (SSA) and steroid-resistant asthma (SRA) groups. They found that serum OX40L level in asthmatic patients (713.5 ± 165.7 pg/mL) was significantly higher than that of the healthy controls (238.6 ± 27.8 pg/mL) (P < 0.001), and significantly higher in SRA group (791.2 ± 167.9 pg/mL) compared to the SSA group (655.6 ± 138.8 pg/mL) (P < 0.001). Furthermore, the serum OX40L level showed a significant positive correlation with serum IgE, blood percentages of eosinophils and neutrophils, serum IL-6 and TSLP, and showed a negative correlation with asthma control test (ACT) score and forced expiratory volume in first second (FEV1%). The authors conclude that this study suggests that high serum OX40L may be a useful biomarker to identify asthmatic patients with corticosteroid resistance.

Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis
Koyama T, Kariya S, Sato Y, Gion Y, Higaki T et al
Allergology International 2019;68(2):216-224. doi: 10.1016/j.alit.2018.09.002
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IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). In light of this association, the authors explored the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS), comparing positive cells in uncinate tissues (UT) and nasal polyps (NP) via use of immunohistochemistry, stratifying by clinicopathological factors.

They found that IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP (especially those from severe ECRS patients) compared to UT. Furthermore, in CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. Also, the number of infiltrating IgG4- positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. Overall, this suggests that that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course.

Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma
Bousquet J, Bedbrook A, Czarlewski W, Onorato GL, Arnavielhe S et al.
Clinical & Translational Allergy 2019;9:16. doi: 10.1186/s13601-019-0252-0
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It is well known that there is a need to support the transformation of the health care system for integrated care with organizational health literacy. MASK (Mobile Airways Sentinel Network) is a new development of ARIA (Allergic Rhinitis and its Impact on Asthma) working closely with POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), and it collaborates with professional and patient organizations in the field of allergy and airway diseases. MASK proposes real-life care pathways (ICPs) centered on the patient with rhinitis and/or asthma. In this article they review their findings from this program, noting several take-home messages, including:

  • Adherence to treatment is the major problem of allergic disease.
  • Self-management strategies should be considerably expanded (behavioral).
  • Change management is essential in allergic diseases.
  • Education strategies should be reconsidered using a patient-centered approach.
  • Lessons learned for allergic diseases can be expanded to chronic diseases.

Comparing biologicals and small molecule drug therapies for chronic respiratory diseases: An EAACI Taskforce on Immunopharmacology position paper
Roth-Walter F, Adcock IM, Benito-Villalvilla C, Bianchini R, Bjermer L et al.
Allergy 2019;74(3):432-448. doi: 10.1111/all.13642
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Chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), result in a significant burden on public health. Increased understanding of molecular mechanisms underlying inflammatory airway disease is being translated into new therapies (as well as hopeful future therapies) for distinct phenotypes not controlled by current treatment regimens. Presently, antibody‚Äźbased (biological) therapies are successful in treating certain respiratory conditions not controlled by standard therapies, such as severe allergic and refractory eosinophilic severe asthma, while in other inflammatory respiratory diseases, such as COPD, biologicals have a more limited impact. Small molecule drug (SMD)-based therapies represent an active field in pharmaceutical research and development. SMDs expand biological therapeutic targets by reaching the intracellular compartment through delivery as either an oral or topically based formulation, offering both convenience and lower costs. In this review the authors compare and contrast the distinct pharmacological properties and clinical applications of SMDs and antibody-based treatment strategies, focusing on both their limitations and challenges, in an attempt to aid the reader in their optimal utilization to fill the critical gaps in current treatment of these illnesses.

Assessment of sleep disturbances and exhaustion in mothers of children with atopic dermatitis
Ramirez FD, Chen S, Langan SM, Prather AA, McCulloch CE et al.
JAMA Dermatology 2019; published online ahead of print (20 March). doi: 10.1001/jamadermatol.2018.5641
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Prior evaluation, based on small, clinic-based studies suggest that sleep loss may be common in parents of children with atopic dermatitis (AD), but longitudinal population-based studies are lacking. In this study, Ramirez and colleagues compared sleep disturbances over time between mothers of children with and without AD, also exploring whether these disturbances were associated with the child’s disease severity and the child’s sleep disturbances by mining data from the Avon Longitudinal Study of Parents and Children. In this study 13,988 mother-child pairs were followed up with a time-varying measure of child AD activity and severity and self-reported maternal sleep measures repeated at multiple time points between child ages 6 months and 11 years. Researchers found that sleep duration (adjusted odds ratio [AOR], 1.09; 95%CI, 0.90-1.32) and early morning awakenings (AOR, 1.16; 95%CI, 0.93-1.46) were similar between mothers of children with and without AD. In contrast, mothers of children with AD were more likely to report difficulty falling asleep (AOR, 1.36; 95%CI, 1.01-1.83), subjectively insufficient sleep (AOR, 1.43; 95%CI, 1.24-1.66), and daytime exhaustion (AOR, 1.41; 95%CI, 1.12-1.78) independent of the child’s comorbid asthma and/or allergic rhinitis. For all measures, worse child AD severity was associated with worse maternal sleep outcomes. The magnitude and significance of the associations were largely unchanged after adjustment for child sleep disturbances. Overall, they found that mothers of children with AD reported difficulty falling asleep, subjectively insufficient sleep, and daytime exhaustion throughout the first 11 years of childhood. The authors stress that when caring for children with AD, clinicians should consider maternal sleep disturbance and associated caregiver fatigue.