Article first published online 6 July 2015.Supplemental Digital Content is Available in the Text.

Intestinal macrophages are uniquely programmed to tolerate exposure to bacteria without mounting potent inflammatory responses. The cytokine IL-10 maintains the macrophage anti-inflammatory response such that loss of IL-10 results in chronic intestinal inflammation. To investigate how IL-10-deficiency alters intestinal macrophage programming and bacterial tolerance, we studied changes in chromatin accessibility in response to bacteria in macrophages from two distinct niches, the intestine and bone-marrow, from both wild-type and IL-10-deficient mice. In both bone-marrow-derived and intestinal macrophages, we identified chromatin accessibility changes associated with bacterial exposure and IL-10-deficiency. Surprisingly, IL-10-deficient intestinal macrophages adopted chromatin and gene expression patterns characteristic of an inflammatory response, even in the absence of bacteria. Further, if IL-10 protein was added to cells that had previously been IL-10-deficient, it could not revert the chromatin landscape to a normal state. Our results demonstrate that IL-10 deficiency results in stable chromatin alterations in macrophages, even in the absence of bacteria. This supports a model where IL-10-deficiency leads to chromatin alterations that contribute to a loss of intestinal macrophage tolerance to bacteria, which is a primary initiating event in chronic intestinal inflammation.

Background Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described. Objective Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF. Methods The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed. Results Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators’ increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS. Conclusions CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging.

Objective Outcome measures in healthcare that presume a higher level of patient health and overall literacy may inadequately estimate the disease experiences of less‐educated patients and further disadvantage them. Patient‐Reported Outcome Measures (PROMs) are widely used communication tools for clinical practice and are often used to evaluate and guide management for chronic rhinosinusitis (CRS) and skull base diseases. However, their readability and subsequent incomprehensibility for patients have not been assessed. The aim of this study is to evaluate the readability of commonly used PROMs for these conditions and whether they meet recommended readability levels. Methods Three readability measures, Gunning Fog, Simple Measure of Gobbledygook (SMOG), and FORCAST were used in the evaluation of commonly used PROMs for CRS and skull base disease. PROMs with sixth‐grade readability level or lower were considered to meet health literacy experts' recommendations. Results A total of 11 PROMs were reviewed (8 CRS, 3 skull base). Gunning Fog consistently estimated the easiest readability, whereas FORCAST the most difficult. One hundred percent of CRS and 67% of skull base PROMs were above National Institutes of Health and health literacy experts' recommended reading levels. PROMs developed more recently had easier readability. Conclusion PROMs are important clinical tools in otolaryngology that help guide management of disease for improved patient‐centered care. Like many other fields of medicine, those used in otolaryngology are beyond recommended reading levels. Development of PROMs in the future should meet recommended readability levels to fully assess the disease experience of our patients. Level of Evidence 4 Laryngoscope, 130:2305–2310, 2020

Objectives/Hypothesis: Patient-reported outcome measures (PROMs) are communication tools to help patients convey their disease experience to medical providers and guide management decisions. However, the utility of healthcare outcome measures is dependent on patient literacy and readability of PROMs. If written for a more advanced literacy level, they can misestimate symptoms and add significant barriers to care, especially in the underserved. However, readability of head and neck (H&N) oncology PROMs has not been assessed. The aim of this study was to evaluate the readability of H&N oncology PROMs to assess whether they meet recommended readability levels. Study Design: Bibliometric review. Methods: Three readability measures: Gunning Fog, Simple Measure of Gobbledygook, and FORCAST were used to evaluate the readability level of commonly used H&N PROMs. PROMs with sixth grade readability level or lower were considered to meet the recommendations of health literacy experts. Results: Eight H&N oncology PROMs were reviewed. None of H&N PROMs met health literacy experts' and National Institutes of Health recommended reading levels. Gunning Fog consistently estimated easiest readability and FORCAST the most difficult. Conclusions: PROMs are important clinical tools that drive patient-centric care in H&N oncology. All H&N PROMs are written above recommended reading levels and do not meet suggested standards. Future PROMs should be written with easier readability to accurately convey patients' H&N oncology disease experiences.

Background Aspirin-exacerbated respiratory disease (AERD) is a subtype of chronic sinusitis comprised of asthma, chronic rhinosinusitis with nasal polyps, and a non-IgE hypersensitivity to cyclooxygenase-1 inhibitors. AERD is typically refractory to medical and often surgical management and causes significant quality-of-life concerns for patients. Objective This study aimed to retrospectively assess the rhinologic disease-specific outcomes as well as quality-of-life metrics in a cohort of AERD patients who medically manage their condition with zileuton, a 5-lipoxygenase inhibitor. Methods Retrospective review of 45 patients at a tertiary care center with diagnosis of AERD who underwent functional endoscopic sinus surgery (FESS) with at least 6 months of pre- and postoperative clinical data were included in the study. Zileuton cohort chosen based on intention-to-treat after initial FESS. Background data collected included patient demographics, surgery information, and zileuton initiation dates. Zileuton and control cohorts were followed for 2.8 and 2.4 years, respectively. Outcomes measured were rhinosinusitis disability index (RSDI) scores, antibiotics use, corticosteroid use, otolaryngology visits, and time to revision surgery. Results RSDI scores, antibiotics use, corticosteroid use, otolaryngology visits, and time to revision surgery had no statistically significant difference between cohorts. However, those taking zileuton tended to undergo fewer revision surgeries during the study. Conclusion Zileuton therapy for AERD patients shows no statistical benefit for rhinologic quality-of-life symptoms but may be useful in diminishing frequency of surgical intervention. In addition, pulmonary symptoms may be improved by treatment but were not assessed. Future study is warranted.

Background Allergic rhinitis is a widespread disease that has significant quality‐of‐life ramifications. Symptoms include rhinorrhea, nasal obstruction, cough, and postnasal drip. Intranasal corticosteroids are a hallmark of treatment of allergic rhinitis. However, the benefits of treatment are dependent on correct nasal spray technique, of which many patients are not aware. Patient instructions are included with the purchase of these medications. The readability and understandability for these educational materials has been minimally assessed in the medical literature. The aim of this study was to evaluate the readability and understandability of commonly used intranasal steroids. Methods Three readability measures (Gunning Fog, Simple Measure of Gobbledygook [SMOG], and FORCAST) and an understandability assessment (Patient Education Materials Assessment Tool for Printable Materials [PEMAT‐P]) were used to evaluate the instructions for use of commonly prescribed intranasal steroids. Instructions with 6th grade readability level or lower were considered to meet health literacy experts’ recommendations. Higher understandability values correlate to easier understandability. Results Instructions for 10 intranasal corticosteroid brands were reviewed. Gunning Fog consistently estimated easiest readability, whereas FORCAST estimated most difficult readability. Twenty percent (20%) of analyzed instructions met National Institutes of Health and health literacy experts’ recommended reading levels. Understandability of instructions ranged from 33% to 90%, with an average of 66%. Conclusion The benefit of intranasal corticosteroids is contingent on correct use by patients. However, the prepackaged instructions provided are most often above recommended reading levels and are difficult to understand. Future development of intranasal steroid instructions should meet recommended readability levels and be understandable to maximize their utility.

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