David M. Manthei

Interferon gene expression in sputum cells correlates with the Asthma Index Score during virus‐induced exacerbations

The majority of asthma exacerbations are related to viral respiratory infections. Some, but not all, previous studies have reported that low interferon responses in patients with asthma increase the risk for virus‐induced exacerbations.

Protection from asthma in a high-risk birth cohort by attenuated P2X7 function

BACKGROUND Viral illnesses are important factors in both asthma inception and exacerbations, and allergic sensitization in early life further enhances asthma risk through unclear mechanisms. Cellular damage caused by infection or allergen inhalation increases ATP levels in the airways with subsequent purinergic receptor activation. The purinergic receptor P2X(7) can enhance airway leukocyte recruitment to the airways, and P2X(7) knockout mice display a reduced asthma-like phenotype. OBJECTIVE Based on the P2X(7) knockout mouse, we hypothesized that children with low P2X(7) function would have decreased rates of asthma. METHODS We used a functional assay to determine P2X(7) pore-producing capacity in whole-blood samples in a birth cohort at high risk for asthma development. The P2X(7) assay was validated with known loss-of-function alleles in human subjects. P2X(7) pore status categorization was used to assess asthma and allergy status in the cohort. RESULTS Attenuated P2X(7) function was associated with lower asthma rates at ages 6 and 8 years, and the greatest effects were observed in boys. Children with asthma at age 11 years who had low P2X(7) capacity had less severe disease in the previous year. Attenuated P2X(7) function was also associated with sensitization to fewer aeroallergens. CONCLUSION P2X(7) functional capacity is associated with asthma risk or disease severity, and these relationships appear to be age related.

Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations

Asthma exacerbations contribute to significant morbidity, mortality and healthcare utilization. Furthermore, viral infections are associated with asthma exacerbations by mechanisms that are not fully understood.

P2X7-Regulated Protection from Exacerbations and Loss of Control Is Independent of Asthma Maintenance Therapy

RATIONALE The function of the P2X(7) nucleotide receptor protects against exacerbation in people with mild-intermittent asthma during viral illnesses, but the impact of disease severity and maintenance therapy has not been studied. OBJECTIVES To evaluate the association between P2X(7), asthma exacerbations, and incomplete symptom control in a more diverse population. METHODS A matched P2RX7 genetic case-control was performed with samples from Asthma Clinical Research Network trial participants enrolled before July 2006, and P2X(7) pore activity was determined in whole blood samples as an ancillary study to two trials completed subsequently. MEASUREMENTS AND MAIN RESULTS A total of 187 exacerbations were studied in 742 subjects, and the change in asthma symptom burden was studied in an additional 110 subjects during a trial of inhaled corticosteroids (ICS) dose optimization. African American carriers of the minor G allele of the rs2230911 loss-of-function single nucleotide polymorphism were more likely to have a history of prednisone use in the previous 12 months, with adjustment for ICS and long-acting β(2)-agonists use (odds ratio, 2.7; 95% confidence interval, 1.2-6.2; P = 0.018). Despite medium-dose ICS, attenuated pore function predicted earlier exacerbations in incompletely controlled patients with moderate asthma (hazard ratio, 3.2; confidence interval, 1.1-9.3; P = 0.033). After establishing control with low-dose ICS in patients with mild asthma, those with attenuated pore function had more asthma symptoms, rescue albuterol use, and FEV(1) reversal (P < 0.001, 0.03, and 0.03, respectively) during the ICS adjustment phase. CONCLUSIONS P2X(7) pore function protects against exacerbations of asthma and loss of control, independent of baseline severity and the maintenance therapy.

Role of food and aeroallergen sensitization in eosinophilic esophagitis in adults

BACKGROUND Evaluation of IgE-mediated food sensitivity is frequently performed for patients with eosinophilic esophagitis (EoE). However, the clinical relevance of identifying IgE-mediated sensitivity to foods in adults is unclear. OBJECTIVE To determine whether EoE associated with food or aeroallergen sensitivity represents a phenotype of EoE with distinct clinical or biological features. METHODS A medical record review identified 257 patients with a diagnosis of EoE evaluated in the adult allergy clinic at the University of Wisconsin Hospital and Clinics from 2008 to 2013. Patient records were reviewed to capture measures of disease severity, endoscopy results, pathology reports, allergy testing, medical management and patient-reported outcomes. RESULTS Evaluation of food sensitization with skin prick testing and/or serum IgE was performed for 93% of patients. Sensitization to at least 1 food was identified in 54% of patients who were more likely to report concomitant asthma, allergic rhinitis, eczema, and/or food allergy compared with nonfood sensitive patients. Aeroallergen sensitivity was identified in 87% of patients tested. Clinical characteristics, including EoE symptoms, disease severity, endoscopic findings, peripheral eosinophilia, and patient-reported outcomes, did not differ between food sensitive and non-food sensitive patients. However, on endoscopy, aeroallergen sensitive patients were more likely to have strictures and less likely to exhibit felinization compared with non-aeroallergen sensitized patients. CONCLUSION Adults with EoE and IgE-mediated food sensitivity are not phenotypically different than non-food sensitive patients. There is no clear clinical utility in identifying food sensitivity in adults with EoE. Further studies are needed to determine whether aeroallergen sensitivity represents a distinct phenotype of EoE.