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Medical Journal Review

August 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.

Patient-burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study
Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Finacier L et al.
Annals of Allergy Asthma and Immunology 2018; pii: S1081-1206(18)30567-2. Article in press. DOI:10.1016/j.anai.2018.07.006

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To better understand the patient burden of atopic dermatitis (AD), this multi-centered cross-sectional, population-based study of 602 adults was performed, relying upon multiple measures, including: AD severity was assessed using self-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Scoring AD (POSCORAD), PO-SCORAD-itch and sleep. QOL was assessed using short-form (SF12-) mental and physical health scores and Dermatology Life Quality Index (DLQI). The authors found that AD places a “heavy burden” on patients, particularly with moderate to severe disease. Specifically, they reported that higher proportions of patients with AD have only fair/poor overall health (25.8% vs. 15.8%), being somewhat/very dissatisfied with life (16.7% vs. 11.4%), lower weighted mean [SD] SF-12 mental (45.9 [9.9] vs. 50.9 [9.2]) and physical health subscores (53.0 [2.5] vs. 53.5 [2.3]) and higher DLQI (4.9 [6.5] vs. 1.1 [2.8]).

In multivariable regression models adjusting for socio-demographics and multiple comorbid health disorders, there were significant stepwise decreases by AD severity (self-reported, POEM, PO-SCORAD) of overall health, life satisfaction, SF-12 mental health and increases of DLQI scores. SF-12 physical health scores were only associated with moderate AD. Concurrently severe PO-SCORAD, POEM and/or PO-SCORAD-itch was associated with very low mean SF-12 mental health (34.7) and high DLQI scores (24.7). AD commonly limited lifestyle (51.3%), led to avoidance of social interaction (39.1%) and impacted activities (43.3%). The most burdensome AD symptoms were itch (54.4%), excessive dryness/scaling (19.6%) and red/inflamed skin (7.2%).

The authors recommend that clinicians incorporate QOL assessments in clinical practice to determine disease-burden, identify AD patients requiring step-up treatment of their skin disease and potentially screen for patients with mental health disturbance.

Outpatient Antibiotic Prescribing for Acute Respiratory Infections During Influenza Seasons
Havers F, Hicks LA, Chung, JR et al.
JAMA Network Open. 2018; 1(2): e180243. doi:10.1001/jamanetworkopen.2018.0243

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It is well known that antibiotics are often wrongly prescribed for acute respiratory infections (ARIs) secondary to viruses. To better understand this issue, the authors attempted to characterize antibiotic prescribing among outpatients with ARI during influenza season and to identify targets for reducing inappropriate antibiotic prescribing for common ARI diagnoses, including among outpatients with laboratory-confirmed influenza. Antibiotic prescriptions, medical history, and International Classification of Diseases, Ninth Revision diagnosis codes were collected from medical and pharmacy records, as were group A streptococcal (GAS) testing results in a patient subset. The defined appropriateness of antibiotic prescribing was based on diagnosis codes, clinical information, and influenza and GAS testing results.

They found that of 14,987 patients with ARI (mean [SD] age, 32 [24] years; 8638 [58%] women; 11,892 [80%] white), 6136 (41%) were prescribed an antibiotic. Among these 6136 patients, 2522 (41%) had diagnoses for which antibiotics are not indicated; 2106 (84%) of these patients were diagnosed as having a viral upper respiratory tract infection or bronchitis (acute or not otherwise specified). Among the 3306 patients (22%) not diagnosed as having pneumonia and who had laboratory confirmed influenza, 945 (29%) were prescribed an antibiotic, accounting for 17% of all antibiotic prescriptions among patients with non-pneumonia ARI. Among 1248 patients with pharyngitis, 1137 (91%) had GAS testing; 440 of the 1248 patients (35%) were prescribed antibiotics, among whom 168 (38%) had negative results on GAS testing. Of 1200 patients with sinusitis and no other indication for antibiotic treatment who received an antibiotic, 454 (38%) had symptoms for 3 days or less prior to the outpatient visit, suggesting acute viral sinusitis not requiring antibiotics.

The authors conclude that overuse of antibiotics remains widespread in the treatment of outpatient ARIs, including among patients with laboratory-confirmed influenza.

Practical guidelines for perioperative hypersensitivity reactions
Laguna JJ, Archilla J, Doña I, Corominas M, Gastaminza G et al.
Journal of Investigational Allergology and Clinical Immunology 2018; 28(4): 216-232. DOI:10.18176/jiaci.0236

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This guideline for the diagnosis and treatment of perioperative anaphylaxis was developed by members of the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology in collaboration with members of the Spanish Anesthesia Society. It provides a wonderful review of the treatment of the acute reaction as well as a logical approach to determining potential cause. Figure 2 is an excellent resource for anesthesiologists to document details regarding a reaction, should one occur.

Association of inadequately controlled disease and disease severity with patient-reported disease burden in adults with atopic dermatitis
Simpson EL, Guttman-Yassky E, Margolis DJ, Feldman SR, Qureshi A et al.
JAMA Dermatology 2018; 154(8): 903-912. DOI:10.1001/jamadermatol.2018.1572

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In attempt to better characterize the patient-reported burden of AD with regard to impact of disease severity and inadequate control in adults, the authors performed a cross-sectional study. They used data from 6 academic medical centers in the United States that were collected by a self-administered Internet-based questionnaire of 1519 adult patients with AD in which disease was stratified by AD severity as mild or moderate/severe using the Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD). The group with moderate/severe disease using systemic immunomodulators/phototherapy were further stratified as having adequate or inadequate disease control.

The authors examined several outcomes, including: validated measures, as well as stand-alone questions assessing itch (pruritus numerical rating scale; PO-SCORAD itch visual analog scale), pain (numerical rating scale), sleep (PO-SCORAD sleep visual analog scale; sleep interference with function), anxiety and depression (Hospital Anxiety and Depression Scale), and health-related quality of life (Dermatology Life Quality Index). They found that of 1519 adult patients with AD, relative to mild AD (n = 689, 64% women; mean [SD] age, 46.5 [18.0] years), those with moderate/severe AD (n = 830, 66.8% women; mean [SD] age, 45.1 [16.9] years) reported more severe itching and pain, greater adverse effects on sleep, higher prevalence of anxiety and depression (417 [50.2%] vs 188 [27.3%]), and greater health-related quality-of-life impairment. The 103 patients with moderate/severe AD with inadequate disease control despite treatment with systemic immunomodulators or phototherapy (55.7%) reported higher burdens of itch and sleeping symptoms vs patients with controlled disease including more days per week with itchy skin (5.7 vs 2.7) and higher proportions with itch duration greater than half a day (190 [22.8%] vs 20 [2.9%]). Sleep symptoms included trouble sleeping (3.9 vs 1.1 on the PO-SCORAD VAS), longer sleep latency (38.8 vs 21.6 minutes), more frequent sleep disturbances (2.6 vs 0.4 nights in past week).

Overall, the results demonstrated that patients with moderate/severe AD reported a significantly greater burden than patients with mild disease on all outcomes, which is further amplified in those with poor disease control. The authors conclude that these results highlight the need for more effective therapies to better control AD, and support the importance of incorporating the patient perspective into assessment of AD beyond using measures of disease activity.

Neutrophil cytoplasts induce Th17 differentiation and skew inflammation toward neutrophilia in severe asthma
Krishnamoorthy N, Douda DN, Bruggemann TR, Ricklefs I, Duvall MG et al.
Science Immunology 2018; 3(26): pii: eaao4747. DOI:10.1126/sciimmunol.aao4747

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It has long been acknowledged that although we have a great understanding of T2 high asthma, many with severe disease are T2 low and our knowledge and treatment options for this subgroup are lackluster. To better understand this phenotype, the authors relied upon a mouse model in which they exposed the mice to aeroallergen and endotoxin which resulted in complex neutrophilic immune responses to allergen alone during later airway challenge.

Specifically, they found that during allergen-mediated responses, the presence of endotoxin triggered lung NETosis with functional roles for the enucleated cytoplasts to convey specific signals of neutrophil activation that served as pivotal effectors for initiation of TH17 differentiation in a transition from innate to adaptive immune responses. Furthermore, cell-cell interactions between neutrophil cytoplasts and dendritic cells (DCs) were found to be spatiotemporally regulated and able to elicit antigen-specific T cell responses with direct relevance to disease pathogenesis for some patients with severe asthma and non–type 2 inflammation.

The authors conclude that their translational results also suggest a broader role for NETosis-derived cytoplasts in initiating TH17-driven adaptive immune responses to pathogens that are crucial to host defense.

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