Sameer K. Mathur

Recent studies on asthma have demonstrated multiple phenotypes, based on the clinical characteristics of the disease. With the current interest in personalized medicine, the question arises whether the presence of allergic sensitization has any relevance for these phenotypes and the management of asthma. This review will examine the current knowledge of asthma phenotypes and the impact of atopy on asthma diagnosis and severity in adults. In addition, this review will address whether therapies targeted at the atopic axis help improve asthma outcomes, including lung function indices and exacerbations.

Summary: Background: 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.Objective: We sought to determine the relationship between lower airway inflammatory biomarkers, specifically interferon gene expression, and the severity or presence of an exacerbation in asthmatics experiencing a naturally occurring viral infection.Methods: Sputum samples were analysed from subjects in an asthma exacerbation study who experienced a confirmed viral infection. Subjects were monitored for daily symptoms, medication use and peak expiratory flow rate until baseline. Sputum samples were assessed for cell counts and gene expression.Results: Interferon gamma expression was significantly greater in patients with asthma exacerbations compared to non‐exacerbating patients (P = 0.002). IFN‐α1, IFN‐β1 and IFN‐γ mRNA levels correlated with the peak Asthma Index (r = 0.58, P < 0.001; r = 0.57, P = 0.001; and r = 0.51, P = 0.004, respectively). Additionally, IL‐13, IL‐10 and eosinophil major basic protein mRNA levels were greater in patients with asthma exacerbations compared to non‐exacerbating patients (P = 0.03, P = 0.06 and P = 0.02, respectively), and IL‐13 mRNA correlated with the peak Asthma Index (P = 0.006).Conclusions: Our findings indicate that asthma exacerbations are associated with increased rather than decreased expression of interferons early in the course of infection. These findings raise the possibility that excessive virus‐induced interferon production during acute infections can contribute to airway inflammation and exacerbations of asthma.

Omalizumab has been shown to be effective in chronic urticaria (CU) patients in numerous reports. However, it remains unknown whether there are specific phenotypes of CU that are more responsive to omalizumab therapy. We sought to identify CU phenotypes responsive to treatment with omalizumab by characterizing patients and their response patterns. A retrospective chart review analysis of refractory CU patients unresponsive to high-dose H₁-blockers and immunomodulators and subsequently treated with omalizumab at the University of Wisconsin Allergy Clinic was performed with particular focus on their autoimmune characteristics, response to therapy, and dosing parameters. We analyzed 19 refractory CU patients (16 patients failed or had toxic side effects to immunomodulators) treated with omalizumab with an overall response rate of 89% (17/19). Of these 19 patients, 9 patients (47%) had a complete response, 8 patients (42%) had a partial response, and 2 patients (11%) had no response. In comparing the response patterns to omalizumab, we found no statistically significant differences among “autoimmune positive” versus “autoimmune negative” patients. No statistically significant differences in responses were observed when comparing demographic parameters including age, gender, IgE levels, or dosing regimen. Our study shows that omalizumab has robust efficacy in refractory CU patients regardless of their autoimmune status, age, gender, IgE levels, or dosing protocol.

Rhinitis symptoms of rhinorrhea, congestion, sneezing, nasal/ocular pruritis, and postnasal drainage can significantly affect the quality of life for older adults. As the US population ages, it will be increasingly important for health-care providers to effectively diagnose and manage rhinitis. Rhinitis is categorized broadly into allergic rhinitis and non-allergic rhinitis. Environmental changes and avoidance measures are a primary means of intervention. In addition, there are several topical therapies (nasal sprays) that can be effective for symptom control.

Background: Thymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation. Therefore, we sought to determine whether TSLP could activate eosinophils, focusing on measuring the regulation of TSLPR expression on eosinophils and degranulation in response to TSLP, as well as other eosinophil activation responses.Methods: Eosinophil mRNA expression of TSLPR and IL-7Rα was examined by real-time quantitative PCR of human eosinophils treated with TNFα and IL-5 family cytokines, and TSLPR surface expression on eosinophils was analyzed by flow cytometry. Eosinophils were stimulated with TSLP (with and without pre-activation with TNFα and IL-3) and evaluated for release of eosinophil derived neurotoxin (EDN), phosphorylation of STAT5, and survival by trypan blue exclusion. A blocking antibody for TSLPR was used to confirm the specificity of TSLP mediated signaling on eosinophil degranulation.Results: Eosinophil expression of cell surface TSLPR and TSLPR mRNA was upregulated by stimulation with TNFα and IL-3. TSLP stimulation resulted in release of EDN, phosphorylation of STAT5 as well as promotion of viability and survival. TSLP-stimulated eosinophil degranulation was inhibited by a functional blocking antibody to TSLPR. Pre-activation of eosinophils with TNFα and IL-3 promoted eosinophil degranulation at lower concentrations of TSLP stimulation.Conclusions: This study demonstrates that eosinophils are activated by TSLP and that eosinophil degranulation in response to TSLP may be enhanced on exposure to cytokines present in allergic inflammation, indicating that the eosinophil has the capacity to participate in TSLP-driven allergic responses.