Mitchell H. Grayson

CysLTR1-expression identifies a subset of neutrophils during the antiviral response that contributes to post-viral atopic airway disease

Background Viral respiratory tract infections increase the risk of development and exacerbation of atopic disease. Previously, we demonstrated the requirement for a neutrophil (PMN) subset expressing CD49d to drive development of postviral atopic airway disease in mice. Objective We sought to determine whether human CD49d+ PMNs are present in the nasal mucosa during acute viral respiratory tract infections and further characterize this PMN subset in human subjects and mice. Methods Sixty subjects (5‐50 years old) were enrolled within 4 days of acute onset of upper respiratory symptoms. Nasal lavage for flow cytometry and nasal swabs for viral PCR were performed at enrollment and during convalescence. The Sendai virus mouse model was used to investigate the phenotype and functional relevance of CD49d+ PMNs. Results CD49d+ PMN frequency was significantly higher in nasal lavage fluid during acute respiratory symptoms in all subjects (2.9% vs 1.0%, n = 42, P < .001). In mice CD49d+ PMNs represented a “proatopic” neutrophil subset that expressed cysteinyl leukotriene receptor 1 (CysLTR1) and produced TNF, CCL2, and CCL5. Inhibition of CysLTR1 signaling in the first days of a viral respiratory tract infection was sufficient to reduce accumulation of CD49d+ PMNs in the lungs and development of postviral atopic airway disease. Similar to the mouse, human CD49d+ PMNs isolated from nasal lavage fluid during a viral respiratory tract infection expressed CysLTR1. Conclusion CD49d and CysLTR1–coexpressing PMNs are present during symptoms of an acute viral respiratory tract infection in human subjects. Further study is needed to examine selective targeting of proatopic neutrophils as a potential therapeutic strategy to prevent development of postviral atopic airway disease. Graphical abstract Figure. No Caption available.

Heterogeneity and the origins of asthma

OBJECTIVEnTo examine the roots of asthma across different ages, including atopy, the role of the microbiome and viral infections, and comorbidities and confounders, such as obesity, aspirin-exacerbated respiratory disease, neutrophilic asthma, cigarette smoking, and the possibility of an asthma-chronic obstructive pulmonary disease overlap syndrome.nnnDATA SOURCESnData were taken from various scientific search engines, including PubMed and Science Direct databases.nnnSTUDY SELECTIONSnArticles that reviewed information on the origins of asthma in persons of all ages, including different phenotypes and genotypes of asthma, were used.nnnRESULTSnAsthma is a common and complex disease whose origins are likely a combination of both genetic predisposition and environmental exposures. Factors such as the microbiome, other atopic disease, viral infections in young children, and other diagnoses, such as obesity or aspirin-exacerbated respiratory disease, are important to consider when creating a treatment plan for patients.nnnCONCLUSIONnAsthma is a disease that is often diagnosed in childhood but can present at any age. There is debate in the field as to whether asthma is one disease or several different diseases that include airway inflammation as a key finding. There are risk factors for disease in the environment and through comorbidities that likely play significant roles in the origins of asthma, the development of symptoms, and the response to treatment. These factors are even more important as we look toward the future with the goal of personalized medicine.

Patient-burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study

BACKGROUNDnThe patient burden and quality of life (QOL) impact of atopic dermatitis (AD) in the United States population is not well established.nnnOBJECTIVEnTo elucidate the patient burden of AD in the US population.nnnMETHODSnA cross-sectional, population-based study of 602 adults was performed. Atopic dermatitis was determined using modified UK Diagnostic Criteria for AD. Its severity was assessed using self-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Scoring AD (PO-SCORAD), PO-SCORAD-itch, and sleep. Quality of life was assessed using short-form (SF-)12 mental and physical health scores and Dermatology Life Quality Index (DLQI).nnnRESULTSnAdults with AD reported higher proportions of having only fair/poor overall health (25.8% vs. 15.8%), being somewhat/very dissatisfied with life (16.7% vs 11.4%), lower weighted mean (standard deviation [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 sociodemographics and multiple comorbid health disorders, 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 were seen. The SF-12 physical health scores were only associated with moderate AD. Concurrently, severe PO-SCORAD, POEM, or PO-SCORAD-itch was associated with very low mean SF-12 mental health (34.7) and high DLQI scores (24.7). Atopic dermatitis 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%).nnnCONCLUSIONnThese data support the heavy burden that AD places on patients, particularly those with moderate and severe AD.

Association of atopic dermatitis with allergic, autoimmune and cardiovascular comorbidities in US adults

BACKGROUNDnAtopic dermatitis (AD) has been associated with multiple comorbid extracutaneous and systemic disorders. The relation between AD severity and disease comorbidities is complex and not fully understood.nnnOBJECTIVEnTo determine the complex relation between AD severity and comorbidities.nnnMETHODSnA cross-sectional US population-based study of 8,217 adults who were participants in a nationally representative internet health panel was performed using a structured questionnaire. A diagnosis of AD was determined using modified United Kingdom Working Party Criteria for AD (nu202f=u202f602). AD severity was assessed using Patient-Oriented Scoring AD, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, and self-reported global AD severity. Logistic regression and structural equation models were used to explore associations of AD with self-reported allergic, cardiometabolic, anxiety and depression, and autoimmune disease.nnnRESULTSnIn multivariable regression models controlling for sociodemographics, AD was associated with higher odds of asthma (adjusted odds ratio [OR] 2.09, 95% confidence interval [CI] 1.71-2.55), hay fever (OR 4.31, 95% CI 3.27-5.69), food allergy (OR 2.07, 95% CI 1.54-2.77), anxiety and depression (OR 2.34, 95% CI 1.91-2.87), autoimmune disease (OR 3.05, 95% CI 2.31-4.03), obesity (OR 1.37, 95% CI 1.13-1.67), diabetes (OR 1.52, 95% CI 1.16-1.99), high blood pressure (OR 1.46, 95% CI 1.18-1.80), and heart disease (OR 1.94, 95% CI 1.40-2.70) compared with controls (P < .01 for all). All these associations were significant in mild and/or moderate disease, with even stronger effects in severe AD. Results of structural equation models showed direct effects of moderate to severe AD on food allergy, anxiety and depression, and diabetes, direct and indirect effects on obesity, and indirect effects on high blood pressure and heart disease.nnnCONCLUSIONnThere is a strong relation of AD severity to allergic, autoimmune, and cardiovascular comorbidities.

Advances in asthma in 2017: Mechanisms, biologics, and genetics

&NA; This review summarizes some of the most significant advances in asthma research over the past year. We first focus on novel discoveries in the mechanism of asthma development and exacerbation. This is followed by a discussion of potential new biomarkers, including the use of radiographic markers of disease. Several new biologics have become available to the clinician in the past year, and we summarize these advances and how they can influence the clinical delivery of asthma care. After this, important findings in the genetics of asthma and heterogeneity in phenotypes of the disease are explored, as is the role the environment plays in shaping the development and exacerbation of asthma. Finally, we conclude with a discussion of advances in health literacy and how they will affect asthma care.

The Allergy Epidemic

Globally, millions of people suffer from allergic diseases, and evidence suggests the prevalence is increasing. This chapter reviews data supporting an “allergy epidemic” demonstrating the increase in atopic disease over the last 50 years. Overall, this trend is evident in Westernized societies, while non-Westernized societies appear to be less affected. Currently it is unclear what is driving this allergy epidemic; however many hypotheses have been developed, including the hygiene, barrier regulation, and microbiome hypotheses. These hypotheses will all be discussed in this chapter. Developing a better understanding of the mechanisms driving atopic disease will lead to novel approaches for disease modification and prevention.

Severity strata for POEM, PO-SCORAD, and DLQI in US adults with atopic dermatitis

BACKGROUNDnPatient-Oriented Eczema Measure (POEM) is the preferred patient-reported outcome (PRO) for assessing symptoms of atopic dermatitis (AD). Dermatology Life Quality Index (DLQI) is commonly used to assess the burden of skin disease. Previous severity strata were developed for POEM and DLQI in clinical cohorts, which may be biased toward more severe disease. Severity strata were not previously examined in population-based cohorts. Patient-Oriented Scoring AD (PO-SCORAD) is another commonly used PRO for assessing AD symptoms; however, severity strata are not established.nnnOBJECTIVEnWe sought to confirm previously developed strata for POEM and DLQI, and to develop strata for the PO-SCORAD in a population-based cohort of adults with AD.nnnMETHODSnA cross-sectional, population-based study of 8,217 adults was performed using a structured questionnaire. A diagnosis of AD was determined using modified UK Diagnostic Criteria for AD (nu202f=u202f602). AD severity was assessed using self-reported global AD severity (anchoring question), POEM, PO-SCORAD, and DLQI. Strata were selected using an anchoring approach based on patient-reported disease severity.nnnRESULTSnWe confirmed the existing strata for DLQI (mildu202f=u202f0-5, moderateu202f=u202f6-10, severeu202f=u202f11-30) (kappau202f=u202f0.446). However, the preferred strata for POEM was mildu202f=u202f0-7, moderateu202f=u202f8-19, and severeu202f=u202f20-28 (kappau202f=u202f0.409) and PO-SCORAD was mildu202f=u202f1-27, moderateu202f=u202f28-56, severeu202f=u202f57-104 (kappau202f=u202f0.444).nnnCONCLUSIONnExisting strata for DLQI performed well in a population-based cohort of adult AD. The optimal severity strata for the POEM in our AD population varies slightly from those previously published for AD. This may suggest that different strata may be optimal in different study settings and cohorts. Finally, we proposed new strata for PO-SCORAD in adult AD.