In Vivo Fluticasone Absorption in Surgical Patients.

BACKGROUND: Intranasal corticosteroids (INCS) are a treatment mainstay of chronic rhinosinusitis and allergic rhinitis. Current computational models demonstrate that >90% of INCS drug deposition occurs on the head of the inferior turbinate and nasal valve, rather than the actual sinuses. These models do not consider mucociliary clearance which propels mucus posteriorly, nor do they consider the absorption of the drug. The purpose of this study is to better understand the exact anatomical location where INCS are absorbed. METHODS: Patients with chronic rhinosinusitis and allergic rhinitis taking fluticasone pre-operatively who were scheduled for functional endoscopic sinus surgery and inferior turbinate reduction, respectively, were recruited. Intra-operative tissue samples were obtained from predetermined locations within the sinonasal cavity. Mass spectrometry was then used to quantify the amount of absorption in each specific anatomic location to determine the largest amount of absorption. RESULTS: Eighteen patients were included in our study. The greatest fluticasone absorption levels across the sinonasal anatomy were at the anterior inferior turbinate (5.7 ngl/mL), ethmoid sinus, (4.4 ng/mL), posterior inferior turbinate (3.7 ng/mL), maxillary sinus (1.3 ng/mL), and the sphenoethmoidal recess (0.72 ng/mL) respectively. Absorption was significantly higher in revision surgery compared to surgically naïve patients. CONCLUSIONS: Computation fluid dynamic models of the nasal passage are useful models to help predict intranasal particle flow. However, these models do not incorporate or consider the important mucociliary clearance system, leading to absorption of fluticasone throughout the sinonasal cavity far beyond that predicted by these models. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1551-1555, 2024.

Sinonasal complications of severe acute respiratory syndrome coronavirus-2: A single center case series.

Background: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in an unprecedented global pandemic. Most infected patients are either asymptomatic or have mild upper respiratory infection symptoms. However, life-threatening sequelae have been observed. In this report, we reviewed nine cases of patients with severe complications from sinonasal disease in the setting of acute SARS-CoV-2 infection. Methods: IRB approval was obtained prior to study initiation. A retrospective chart review was performed of patients admitted to a tertiary hospital with complex sinonasal symptoms that required otolaryngologic evaluation and management in the setting of concomitant SARS-CoV-2 infection. Results: Nine patients, ranging from ages 3 to 71 years, with sinonasal disease and simultaneous SARS-CoV-2 infection were identified. Initial presentations ranged from asymptomatic infection to mild/moderate disease (nasal obstruction, cough) or more severe sequelae including epistaxis, proptosis, or neurologic changes. SARS-CoV-2 tests were positive from one to 12 days after symptom onset, with three patients receiving SARS-CoV-2-directed treatment. Complex disease presentations included bilateral orbital abscesses, suppurative intracranial infection, cavernous sinus thrombosis with epidural abscess, systemic hematogenous spread with abscess development in four distinct anatomic locations, and hemorrhagic benign adenoidal tissue. Eight of nine patients (88.8%) required operative intervention. Patients with abscesses also required prolonged, culture-directed antibiotic courses. Conclusion: Though most SARS-CoV-2 infections are asymptomatic and/or self-limited, there is significant morbidity and mortality in patients with severe disease sequela as outlined in our reported cases. This suggests early identification and treatment of sinonasal disease in this patient population is critical to minimizing poor outcomes. Further research on the pathophysiology of these atypical presentations is needed. Level of Evidence: 4 (Case Series).

Availability of Readable Online Spanish Rhinosinusitis Outcome Measures.

BACKGROUND: Patient-reported outcome measures (PROMs) are useful instruments that give providers insight into patients' experiences with disease by quantifying the symptoms that matter most to patients. Results of these questionnaires can help guide management in chronic rhinosinusitis. However, these tools are often developed for native English speakers, which disadvantages others, who already have a language barrier to care. The aim of this study is to evaluate accessibility and readability of Spanish PROMs used to evaluate rhinosinusitis. METHODS: Three Spanish readability measures, Gilliam, Peña & Mountain; SOL; and Fernandez-Huerta were used to evaluate PROMs utilized for rhinosinusitis. PROMs with sixth-grade readability level or easier were considered to meet health literacy recommendations. RESULTS: Four Spanish PROMs utilized in assessment of rhinosinusitis were identified and evaluated. Cuestionario Español de Calidad de Vida en Rinitis (ESPRINT-15) was the most readable PROM and met readability recommendations in two of three measures. Nasal Obstruction Symptom Evaluation met suggested levels in one measure. The remainder of readability scores were more difficult than recommended. CONCLUSION: PROMs are powerful clinical tools that help patients communicate their symptoms and self-advocate. For providers to gain accurate and useful information, these measures should be written at appropriate readability levels. Most Spanish PROMs used for assessment of rhinosinusitis were above recommended readability. Development of future PROMs should ensure appropriate readability levels to provide good patient-centered care for our primarily Spanish speaking patients.

Readability analysis of pediatric otolaryngology patient-reported outcome measures.

OBJECTIVE: (s): Patient-reported outcome measures (PROMs) are tools that allow patients to directly share information about their health with their healthcare provider. Health literacy experts recommend that health information, such as PROMs, be written at a 6th grade level to ensure patients can read and comprehend it. As the readability of PROMs used in pediatric otolaryngology has yet to be studied, our goal was to analyze the readability of these PROMs and assess their compliance with readability recommendations. METHODS: The Gunning Fog, the Simple Measure of Gobbledygook (SMOG), and the FORCAST readability formulas were used to determine the readability of disease-specific PROMs for pediatric otolaryngology. RESULTS: Fourteen PROMs were reviewed in the study. Most were intended for caregiver completion (n = 13, 92.9%). Ten PROMs when measured by Gunning Fog (71.4%), 2 PROMs when measured by SMOG (14.3%), and 0 PROMs when measured by FORCAST (0.0%) were at or below the 6th grade reading level. CONCLUSION: Most PROMs available for use in pediatric otolaryngology are above the recommended 6th grade reading level when measured by FORCAST, the most appropriate metric for assessing questionnaires. The high reading grade level needed to complete these PROMs can contribute to health disparities among underserved and vulnerable populations, such as children. Pediatric otolaryngology PROMs developed in the future should take readability into account in order to ensure equity in the delivery of care.

Prolonged Implantation of Sinus Devices and Implications for Chronic Rhinosinusitis: A Case Report and Review of the Literature.

BACKGROUND: Implantation of sinus stents and spacers can be used as adjuvant management to maintain patency of sinuses after endoscopic sinus surgery for chronic rhinosinusitis. These implants are typically removed several weeks after surgery. We present two cases of different patients who were initially treated by different physicians and were found to have retained sinus spacers in their paranasal sinuses 6-10 years after implantation. CASE PRESENTATION: Case 1: a 40-year old male with chronic rhinosinusitis and history of balloon sinuplasty six years prior presented with worsening symptoms of chronic rhinosinusitis refractory to medical management. He underwent revision functional endoscopic sinus surgery and was found to have retained sinus implants in the left and right frontal sinus recesses. Case 2: a 48-year-old female with long-standing chronic rhinosinusitis refractory to medical management presented after two prior sinus surgeries most recently 10 years ago. She underwent revision functional endoscopic surgery and was found to have a retained sinus implant from prior surgery in the right frontal recess outflow tract embedded within scar tissue and reactive hyperostosis. Foreign bodies from both patients were removed without complication and patients were healing appropriately in the post-operative period. CONCLUSIONS: While sinus stents and spacers can help with post-operative scarring, leaving then unmonitored and in place will eventually result in them becoming a nidus for scarring and infection. It is critical that patients are aware of any foreign bodies we place, if they need scheduled removal or routine observation, and what symptoms may indicate that they are causing a problem.

Understood? Evaluating the readability and understandability of intranasal corticosteroid delivery instructions.

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.

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist.

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.

Readability of Patient-Reported Outcome Measures for Head and Neck Oncology.

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. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

Readability of patient-reported outcome measures for chronic rhinosinusitis and skull base diseases.

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.

Alterations to chromatin in intestinal macrophages link IL-10 deficiency to inappropriate inflammatory responses.

Intestinal macrophages (IMs) 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 IM 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 (Il10(-/-) ) mice. We identified chromatin accessibility changes associated with bacterial exposure and IL-10 deficiency in both bone marrow derived macrophages and IMs. Surprisingly, Il10(-/-) IMs adopted chromatin and gene expression patterns characteristic of an inflammatory response, even in the absence of bacteria. Further, when recombinant IL-10 was added to Il10(-/-) cells, 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 in which IL-10-deficiency leads to chromatin alterations that contribute to a loss of IM tolerance to bacteria, which is a primary initiating event in chronic intestinal inflammation.

MicroRNAs Classify Different Disease Behavior Phenotypes of Crohn's Disease and May Have Prognostic Utility.

BACKGROUND: There is a dire need for reliable prognostic markers that can guide effective therapeutic intervention in Crohn's disease (CD). We examined whether different phenotypes in CD can be classified based on colonic microRNA (miRNA) expression and whether miRNAs have prognostic utility for CD. METHODS: High-throughput sequencing of small and total RNA isolated from colon tissue from patients with CD and controls without Inflammatory Bowel Disease (non-IBD) was performed. To identify miRNAs associated with specific phenotypes of CD, patients were stratified according to disease behavior (nonstricturing, nonpenetrating; stricturing; penetrating), and miRNA profiles in each subset were compared with those of the non-IBD group. Validation assays were performed using quantitative reverse transcription polymerase chain reaction. These miRNAs were further evaluated by quantitative reverse transcriptase polymerase chain reaction on formalin-fixed, paraffin-embedded tissue (index biopsies) of patients with nonpenetrating CD at the time of diagnosis that either retained the nonpenetrating phenotype or progressed to penetrating/fistulizing CD. RESULTS: We found a suite of miRNAs, including miR-31-5p, miR-215, miR-223-3p, miR-196b-5p, and miR-203 that stratify patients with CD according to disease behavior independent of the effect of inflammation. Furthermore, we also demonstrated that expression levels of miR-215 in index biopsies of patients with CD might predict the likelihood of progression to penetrating/fistulizing CD. Finally, using a novel statistical simulation approach applied to colonic RNA-sequencing data for patients with CD and non-IBD controls, we identified miR-31-5p and miR-203 as candidate master regulators of gene expression profiles associated with CD. CONCLUSIONS: miRNAs may serve as clinically useful prognostic markers guiding initial therapy and identifying patients who would benefit most from effective intervention.