Minimally invasive biomarker studies in eosinophilic esophagitis: A systematic review

Publication date: August 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 2

Author(s): Brittany T. Hines, Matthew A. Rank, Benjamin L. Wright, Lisa A. Marks, John B. Hagan, Alex Straumann, Matthew Greenhawt, Evan S. Dellon

Abstract

Background

Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus that currently requires repeated endoscopic biopsies for diagnosis and monitoring because no reliable noninvasive markers have been identified.

Objective

To identify promising minimally invasive EoE biomarkers and remaining gaps in biomarker validation.

Methods

We performed a systematic review of EMBASE, Ovid MEDLINE, PubMed, and Web of Science from inception to June 6, 2017. Studies were included if patients met the 2007 consensus criteria for EoE diagnosis, a minimally invasive biomarker was assessed, and the study included at least 1 control for comparison.

Results

The search identified 2094 studies, with 234 reviewed at full-text level, and 49 included in the analysis (20 adult, 19 pediatric, 7 pediatric and adult, and 3 not stated). Most (26 of 49) were published after 2014. Thirty-five studies included healthy controls, 9 analyzed atopic controls, and 29 compared samples from patients with active and inactive EoE. Minimally invasive biomarkers were obtained from peripheral blood (n = 41 studies), sponge or string samples (n = 3), oral or throat swab secretions (n = 2), breath condensate (n = 2), stool (n = 2), and urine (n = 2). The most commonly reported biomarkers were peripheral blood eosinophils (n = 16), blood and string eosinophil granule proteins (n = 14), and eosinophil surface or intracellular markers (n = 12). EoE biomarkers distinguished active EoE from healthy controls in 23 studies, atopic controls in 2 studies, and inactive EoE controls in 20 studies.

Conclusion

Several promising minimally invasive biomarkers for EoE have emerged; however, few are able to differentiate EoE from other atopic diseases.

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Bedroom exposure to airborne allergens in the Chicago area using a patient-operated sampling device

Publication date: August 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 2

Author(s): Julian Gordon, Paul Detjen, Sai Nimmagadda, Laura Rogers, Sanjay Patel, James Thompson, Rachel Reboulet, Prasanthi Gandhi

Abstract

Background

In current practice, allergens in vacuum-collected dust are used as surrogates for inhalable allergens. We developed an air-sampling device that can be used by patients for direct measurement of airborne allergen concentrations in their own homes.

Objective

To demonstrate the use of this device to establish allergen concentration reference ranges in a target population and to evaluate associations between patient-reported information and measured allergen concentrations.

Methods

Patients from 5 allergist's practices in the Chicagoland region were provided with instructions, questionnaires, informed consent forms, and samplers to run for 5 days in their bedrooms. Samples were collected from cartridges and assayed by multiplex immunoassays for 12 common household allergens and enzyme-linked immunosorbent assay for ragweed.

Results

Unique allergen profiles were obtained for 102 patient homes. Samples with allergen concentrations above the limit of detection were as follows: total dust mite, 28%; cat, 61%; dog, 64%; mouse, 12%; rat, 0%; cockroach, 4%; Alternaria, 6%; Aspergillus, 21%; birch pollen 1%; grass, 8%; and ragweed, 5%. Of those, 75 completed questionnaires, providing meta-data for further analysis. Pet allergens correlated significantly with number of pets owned. Humidity correlated with dust mite allergens, open windows with Alternaria and mouse allergens, and high-efficiency particulate air filter use with reduced levels of several allergens. Many other variables showed no significant correlations.

Conclusion

The combination of ease of use, high air-sampling rate, and sensitive immunoassays permitted the measurement of airborne allergen concentrations in homes and establishment of reference ranges. Patient-reported information permitted identification of factors that could relate to allergen concentrations and suggested remedial measures.

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Aspergillus fumigatus viability drives allergic responses to inhaled conidia

Publication date: August 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 2

Author(s): Ajay P. Nayak, Tara L. Croston, Angela R. Lemons, W.T. Goldsmith, Nikki B. Marshall, Michael L. Kashon, Dori R. Germolec, Donald H. Beezhold, Brett J. Green

Abstract

Background

Aspergillus fumigatus–induced allergic airway disease has been shown to involve conidial germination in vivo, but the immunological mechanisms remain uncharacterized.

Objective

A subchronic murine exposure model was used to examine the immunological mediators that are regulated in response to either culturable or nonculturable A fumigatus conidia.

Methods

Female B6C3F1/N mice were repeatedly dosed via inhalation with 1 × 105 viable or heat-inactivated conidia (HIC), twice per week for 13 weeks (26 exposures). Control mice inhaled high-efficiency particulate arrestor–filtered air. The influence of A fumigatus conidial germination on the pulmonary immunopathological outcomes was evaluated by flow cytometry analysis of cellular infiltration in the airways, assessment of lung messenger RNA expression, quantitative proteomics, and histopathology of whole lung tissue.

Results

Repeated inhalation of viable conidia, but not HIC, resulted in allergic inflammation marked by vascular remodeling, extensive eosinophilia, and accumulation of alternatively activated macrophages (AAMs) in the murine airways. More specifically, mice that inhaled viable conidia resulted in a mixed TH1 and TH2 (IL-13) cytokine response. Recruitment of eosinophils corresponded with increased Ccl11 transcripts. Furthermore, genes associated with M2 or alternatively activated macrophage polarization (eg, Arg1, Chil3, and Retnla) were significantly up-regulated in viable A fumigatus–exposed mice. In mice inhaling HIC, CD4+ T cells expressing IFN-γ (TH1) dominated the lymphocytic infiltration. Quantitative proteomics of the lung revealed metabolic reprogramming accompanied by mitochondrial dysfunction and endoplasmic reticulum stress stimulated by oxidative stress from repetitive microbial insult.

Conclusion

Our studies demonstrate that A fumigatus conidial viability in vivo is critical to the immunopathological presentation of chronic fungal allergic disease.

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Changes in chronic rhinosinusitis symptoms differentially associate with improvement in general health-related quality of life

Publication date: August 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 2

Author(s): Marlene M. Speth, Lloyd P. Hoehle, Katie M. Phillips, David S. Caradonna, Stacey T. Gray, Ahmad R. Sedaghat

Abstract

Background

Previous work has shown that the symptoms of chronic rhinosinusitis (CRS) differentially associate with decreased general health-related quality of life (QOL).

Objective

We sought to determine whether longitudinal changes in different types of CRS symptomatology lead to correspondingly different magnitude changes in general health-related QOL.

Methods

Prospective observational study of 145 patients undergoing medical management for CRS. Chronic rhinosinusitis symptom severity was measured using the 22-item Sinonasal Outcome Test (SNOT-22) and associated nasal, sleep, ear/facial discomfort, and emotional subdomains of the SNOT-22. General health-related QOL was measured using the 5-dimensional EuroQoL questionnaire's visual analog scale (EQ-5D VAS). These data were collected at 2 time points: at enrollment and at a subsequent follow-up visit within the next 2 to 6 months. Associations were sought between the changes in SNOT-22 and EQ-5D VAS.

Results

The change in SNOT-22 was associated with change in EQ-5D VAS (adjusted linear regression coefficient [β] = −0.37, 95%CI: −0.51 to −0.24, P < .001). The change in EQ-5D VAS was only associated with changes in the sleep (adjusted β = −0.42, 95% confidence interval [95%CI]: −0.81 to −0.04, P = .034) and ear/facial discomfort (adjusted β = −1.00, 95%CI: −1.89 to −0.10, P = .031) subdomains but not nasal (adjusted β = −0.12, 95%CI: −0.52 to 0.28, P = .564) or emotional (adjusted β = −0.17, 95%CI: −1.83 to 1.49, P = .840) subdomains.

Conclusion

Changes in the severity of sleep and ear/facial discomfort symptoms associate most greatly with the change in general health-related QOL that CRS patients experience during routine medical management. Reduction of these extranasal symptoms of CRS may therefore lead to the greatest improvement in general health-related QOL.

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Efficacy of add-on sublingual immunotherapy for adults with asthma: A meta-analysis and systematic review

Publication date: August 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 2

Author(s): Kan Xu, Zhi Deng, Dandan Li, Honglei Yuan, Cheng Liu, Zhihong Chen, Lei Zhu

Abstract

Background

Sublingual immunotherapy (SLIT) reduces symptom scores and the use of rescue medication in children with allergic asthma, but the effect of SLIT therapy in adult patients has not been reported.

Objective

To examine the efficacy and adverse effects of SLIT add-on vs conventional medication in adult patients with mild to moderate asthma.

Methods

We systematically searched the MEDLINE, Embase, Cochrane, and Central databases. Eligible studies included adult patients with allergic asthma who received either SLIT or standard care. Standard mean differences were used as measures of efficacy in a random-effects model.

Results

Twenty trials that included 2,288 patients in the SLIT add-on group and 1,268 patients in the traditional therapy group were identified as eligible for final analysis. Compared with traditional therapy, SLIT add-on therapy was associated with significant improvements in lower and upper airway scores, a higher forced expiratory volume in 1 second, and maximal expiratory flow at 25% of forced vital capacity, and improved bronchial reactivity. Drug consumptions were significantly decreased as well. Airway inflammatory parameters, such as nasal eosinophil infiltration, were markedly improved.

Conclusion

The findings of this study suggested that long-term SLIT add-on therapy is a complementary treatment for adults with asthma in addition to conventional medicine. It not only reduces symptom scores but also improves lung function and airway inflammation.

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Hypereosinophilic syndrome in the differential diagnosis of pulmonary infiltrates with eosinophilia

Publication date: August 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 2

Author(s): Nives Zimmermann, Kathryn A. Wikenheiser-Brokamp

Abstract

Objective

To describe key diagnostic considerations in patients with pulmonary infiltrates with eosinophilia, with a special emphasis on raising awareness of hypereosinophilic syndrome (HES), a disease that often involves the lungs and prompts investigation for clonal neoplastic processes that determine prognosis and treatment.

Data Sources

Studies and review articles were selected from PubMed and Scopus for relevance to pertinent topics.

Study Selections

The literature was screened for studies that described lung eosinophilia and HES. Studies relevant to the topic were included in this review.

Results

Pulmonary eosinophil infiltrates in lung biopsy specimens present a broad differential diagnosis, including eosinophilic pneumonia; hypersensitivity reactions, such as allergic bronchopulmonary fungal disease; and pulmonary manifestations of systemic diseases, such as eosinophilic granulomatosis with polyangiitis. An additional important consideration in the differential diagnosis is pulmonary involvement by HES. HES is a rare syndrome that comprises a heterogeneous group of conditions characterized by persistent blood and/or tissue eosinophilia associated with organ dysfunction. Approximately one-third of HES cases are caused by neoplastic diseases, with the remaining cases classified as reactive or idiopathic. Lung involvement is seen in up to 67% of cases and may be the presenting manifestation of the disorder.

Conclusion

The differential diagnosis of pulmonary eosinophilia is broad and requires a multidisciplinary approach with clinicopathologic-radiologic correlation.

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Current trends in food allergy–induced anaphylaxis management at school

Publication date: August 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 2

Author(s): Matthew Greenhawt, Dana Wallace, J. Wesley Sublett, Erin Maughan, Andrea Tanner, Kevin J. Kelley, Stanley Fineman, Martha White, Gene Cash, Charmayne Anderson, Sally Schoessler, Ruchi Gupta, Michael Pistiner

Abstract

Objective

To review the evidence and current policies regarding the use of epinephrine at schools and child care centers

Data Sources and Study Selections

A narrative review was performed based on the result of conference proceedings of a group of interprofessional stakeholders who attended the USAnaphylaxis Summit 2017 presented by Allergy & Asthma Network.

Results

Anaphylaxis is a well-recognized medical emergency that requires prompt treatment with intramuscular epinephrine. Anaphylaxis can be associated with poor quality of life. There is renewed recent focus on anaphylaxis management in schools. This interest has been spurred by an increase in the number of children with food allergy who are attending school, data that support up to 25% of first-time anaphylactic events occurring on school grounds, and a well-publicized fatality that helped to initiate a movement for stock, undesignated, non–student-specific epinephrine. Stock epinephrine is now available in 49 states, with an increasing number of states instituting mandatory reporting for use of such devices. Nursing efforts are paramount to support and implement stock epinephrine programs. Many states do not have clarity on delegation of authority for who can administer stock epinephrine, and there is evidence of variability in storage of stock devices. Few states have outcomes data that support successful implementation of stock epinephrine programs.

Conclusion

Additional data are needed to demonstrate successful implementations of stock epinephrine programs and their outcomes. Such programs should include support for school nursing and clearer delineation of authority for medication administration as well as standards for where and how devices are stored.

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