Association between particulate matter containing EPFRs and neutrophilic asthma through AhR and Th17.

BACKGROUND: Epidemiological data associate high levels of combustion-derived particulate matter (PM) with deleterious respiratory outcomes, but the mechanism underlying those outcomes remains elusive. It has been acknowledged by the World Health Organization that PM exposure contributes to more than 4.2 million all-cause mortalities worldwide each year. Current literature demonstrates that PM exacerbates respiratory diseases, impairs lung function, results in chronic respiratory illnesses, and is associated with increased mortality. The proposed mechanisms revolve around oxidative stress and inflammation promoting pulmonary physiological remodeling. However, our previous data found that PM is capable of inducing T helper cell 17 (Th17) immune responses via aryl hydrocarbon receptor (Ahr) activation, which was associated with neutrophilic invasion characteristic of steroid insensitive asthma. METHODS: In the present study, we utilized a combination of microarray and single cell RNA sequencing data to analyze the immunological landscape in mouse lungs following acute exposure to combustion derived particulate matter. RESULTS: We present data that suggest epithelial cells produce specific cytokines in the aryl hydrocarbon receptor (Ahr) pathway that inform dendritic cells to initiate the production of pathogenic T helper (eTh17) cells. Using single-cell RNA sequencing analysis, we observed that upon exposure epithelial cells acquire a transcriptomic profile indicative of increased Il-17 signaling, Ahr activation, Egfr signaling, and T cell receptor and co-stimulatory signaling pathways. Epithelial cells further showed, Ahr activation is brought on by Ahr/ARNT nuclear translocation and activation of tyrosine kinase c-src, Egfr, and subsequently Erk1/2 pathways. CONCLUSIONS: Collectively, our data corroborates that PM initiates an eTh17 specific inflammatory response causing neutrophilic asthma through pathways in epithelial, dendritic, and T cells that promote eTh17 differentiation during initial PM exposure.

The impact of teach-back on comprehension of discharge instructions and satisfaction among emergency patients with limited health literacy: A randomized, controlled study.

OBJECTIVE: Recommended as a 'universal precaution' for improving provider-patient communication, teach-back has a limited evidence base. Discharge from the emergency department (ED) to home is an important high-risk transition of care with potential for miscommunication of critical information. We examined whether teach-back improves: comprehension and perceived comprehension of discharge instructions and satisfaction among patients with limited health literacy (LHL) in the ED. METHODS: We performed a randomized, controlled study among adult patients with LHL, to teach-back or standard discharge instructions. Patients completed an audio-recorded structured interview evaluating comprehension and perceived comprehension of (1) diagnosis, (2) ED course, (3) post-ED care, and (4) reasons to return and satisfaction using four Consumer Assessment of Healthcare Providers and Systems questions. Concordance with the medical record was rated using a five-level scale. We analyzed differences between groups using multivariable ordinal logistic regression. RESULTS: Patients randomized to receive teach-back had higher comprehension of post-ED care areas: post-ED medication (P < 0.02), self-care (P < 0.03), and follow-up instructions (P < 0.0001), but no change in patient satisfaction or perceived comprehension. CONCLUSION: Teach-back appears to improve comprehension of post-ED care instructions but not satisfaction or perceived comprehension. Our data from a randomized, controlled study support the effectiveness of teach-back in a busy clinical setting. Further research is needed to test the utility and feasibility of teach-back for routine use including its impacts on distal outcomes.