Genome-Wide Methylation Study Identifies an IL-13-induced Epigenetic Signature in Asthmatic Airways.

RATIONALE: Epigenetic changes to airway cells have been proposed as important modulators of the effects of environmental exposures on airway diseases, yet no study to date has shown epigenetic responses to exposures in the airway that correlate with disease state. The type 2 cytokine IL-13 is a key mediator of allergic airway diseases, such as asthma, and is up-regulated in response to many asthma-promoting exposures. OBJECTIVES: To directly study the epigenetic response of airway epithelial cells (AECs) to IL-13 and test whether IL-13-induced epigenetic changes differ between individuals with and without asthma. METHODS: Genome-wide DNA methylation and gene expression patterns were studied in 58 IL-13-treated and untreated primary AEC cultures and validated in freshly isolated cells of subjects with and without asthma using the Illumina Human Methylation 450K and HumanHT-12 BeadChips. IL-13-mediated comethylation modules were identified and correlated with clinical phenotypes using weighted gene coexpression network analysis. MEASUREMENTS AND MAIN RESULTS: IL-13 altered global DNA methylation patterns in cultured AECs and were significantly enriched near genes associated with asthma. Importantly, a significant proportion of this IL-13 epigenetic signature was validated in freshly isolated AECs from subjects with asthma and clustered into two distinct modules, with module 1 correlated with asthma severity and lung function and module 2 with eosinophilia. CONCLUSIONS: These results suggest that a single exposure of IL-13 may selectively induce long-lasting DNA methylation changes in asthmatic airways that alter specific AEC pathways and contribute to asthma phenotypes.

Misuse of respiratory inhalers in hospitalized patients with asthma or COPD.

BACKGROUND: Patients are asked to assume greater responsibility for care, including use of medications, during transitions from hospital to home. Unfortunately, medications dispensed via respiratory inhalers to patients with asthma or chronic obstructive pulmonary disease (COPD) can be difficult to use. OBJECTIVES: To examine rates of inhaler misuse and to determine if patients with asthma or COPD differed in their ability to learn how to use inhalers correctly. DESIGN: A cross-sectional and pre/post intervention study at two urban academic hospitals. PARTICIPANTS: Hospitalized patients with asthma or COPD. INTERVENTION: A subset of participants received instruction about the correct use of respiratory inhalers. MAIN MEASURES: Use of metered dose inhaler (MDI) and Diskus devices was assessed using checklists. Misuse and mastery of each device were defined as <75% and 100% of steps correct, respectively. Insufficient vision was defined as worse than 20/50 in both eyes. Less-than adequate health literacy was defined as a score of <23/36 on The Short Test of Functional Health Literacy in Adults (S-TOFHLA). KEY RESULTS: One-hundred participants were enrolled (COPD n = 40; asthma n = 60). Overall, misuse was common (86% MDI, 71% Diskus), and rates of inhaler misuse for participants with COPD versus asthma were similar. Participants with COPD versus asthma were twice as likely to have insufficient vision (43% vs. 20%, p = 0.02) and three-times as likely to have less-than- adequate health literacy (61% vs. 19%, p = 0.001). Participants with insufficient vision were more likely to misuse Diskus devices (95% vs. 61%, p = 0.004). All participants (100%) were able to achieve mastery for both MDI and Diskus devices. CONCLUSIONS: Inhaler misuse is common, but correctable in hospitalized patients with COPD or asthma. Hospitals should implement a program to assess and teach appropriate inhaler technique that can overcome barriers to patient self-management, including insufficient vision, during transitions from hospital to home.