Stephanie Shintani-Smith

A pilot study of symptom profiles from a polyp vs an eosinophilic-based classification of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is likely a biologically heterogeneous disease process. Current guidelines propose subclassification using polyp status while others propose using mucosal eosinophilia. We hypothesized that appropriate CRS subclassification would increase homogeneity of baseline symptoms, and identify characteristic symptoms of each subtype.

Identifying clinical symptoms for improving the symptomatic diagnosis of chronic rhinosinusitis

Current symptom criteria for identifying patients with chronic rhinosinusitis (CRS) has poor specificity. The objective of this study was to test the hypothesis that symptoms drawn from the Task Force on Rhinosinusitis (RSTF) criteria and the International Headache Society (IHS) criteria for primary headaches can differentiate CRS patients from those with CRS‐symptoms but no evidence for inflammation (non‐CRS).

Imaging of cochlear tissue with a grating interferometer and hard X-rays

This article addresses an important current development in medical and biological imaging: the possibility of imaging soft tissue at resolutions in the micron range using hard X‐rays. Challenging environments, including the cochlea, require the imaging of soft tissue structure surrounded by bone. We demonstrate that cochlear soft tissue structures can be imaged with hard X‐ray phase contrast. Furthermore, we show that only a thin slice of the tissue is required to introduce a large phase shift. It is likely that the phase contrast image of the soft tissue structures is sufficient to image the structures even if surrounded by bone. For the present set of experiments, structures with low‐absorption contrast have been visualized using in‐line phase contrast imaging and a grating interferometer. The experiments have been performed at the Advanced Photon Source at Argonne National Laboratories, a third generation source of synchrotron radiation. The source provides highly coherent X‐ray radiation with high‐photon flux (>1012 photons/s) at high‐photon energies (5–70 keV). Radiographic and light microscopy images of the gerbil cochlear slice samples were compared. It has been determined that a 20‐μm thick tissue slice induces a phase shift between 1/3π and 2/3π. Microsc. Res. Tech., 2009.

Effect of symptom-based risk stratification on the costs of managing patients with chronic rhinosinusitis symptoms.

Current symptom criteria poorly predict a diagnosis of chronic rhinosinusitis (CRS) resulting in excessive treatment of patients with presumed CRS. The objective of this study was analyze the positive predictive value of individual symptoms, or symptoms in combination, in patients with CRS symptoms and examine the costs of the subsequent diagnostic algorithm using a decision tree–based cost analysis.

Chronic Airway Inflammation Provides a Unique Environment for B Cell Activation and Antibody Production

B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of CRS patients develop nasal polyps (NPs), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2s). We have reported that NP contain elevated levels of B cells and antibodies, making NP an ideal system for studying B cells in the airways.

Neutrophils are a major source of the epithelial barrier disrupting cytokine oncostatin M in patients with mucosal airways disease

Background We have previously shown that oncostatin M (OSM) levels are increased in nasal polyps (NPs) of patients with chronic rhinosinusitis (CRS), as well as in bronchoalveolar lavage fluid, after segmental allergen challenge in allergic asthmatic patients. We also showed in vitro that physiologic levels of OSM impair barrier function in differentiated airway epithelium. Objective We sought to determine which hematopoietic or resident cell type or types were the source of the OSM expressed in patients with mucosal airways disease. Methods Paraffin‐embedded NP sections were stained with fluorescence‐labeled specific antibodies against OSM, GM‐CSF, and hematopoietic cell‐specific markers. Live cells were isolated from NPs and matched blood samples for flow cytometric analysis. Neutrophils were isolated from whole blood and cultured with the known OSM inducers GM‐CSF and follistatin‐like 1, and OSM levels were measured in the supernatants. Bronchial biopsy sections from control subjects, patients with moderate asthma, and patients with severe asthma were stained for OSM and neutrophil elastase. Results OSM staining was observed in NPs, showed colocalization with neutrophil elastase (n = 10), and did not colocalize with markers for eosinophils, macrophages, T cells, or B cells (n = 3‐5). Flow cytometric analysis of NPs (n = 9) showed that 5.1% ± 2% of CD45+ cells were OSM+, and of the OSM+ cells, 56% ± 7% were CD16+Siglec‐8−, indicating neutrophil lineage. Only 0.6 ± 0.4% of CD45+ events from matched blood samples (n = 5) were OSM+, suggesting that increased OSM levels in patients with CRS was locally stimulated and produced. A majority of OSM+ neutrophils expressed arginase 1 (72.5% ± 12%), suggesting an N2 phenotype. GM‐CSF levels were increased in NPs compared with those in control tissue and were sufficient to induce OSM production (P < .001) in peripheral blood neutrophils in vitro. OSM+ neutrophils were also observed at increased levels in biopsy specimens from patients with severe asthma. Additionally, OSM protein levels were increased in induced sputum from asthmatic patients compared with that from control subjects (P < .05). Conclusions Neutrophils are a major source of OSM‐producing cells in patients with CRS and severe asthma.

Classical complement pathway activation in the nasal tissue of patients with chronic rhinosinusitis

Background Complement plays a major role in inflammatory diseases, but its involvement and mechanisms of activation in patients with chronic rhinosinusitis (CRS) are not known. Objectives After earlier studies discovering autoantibodies in patients with CRS, we sought to investigate the nature, extent, and location of complement activation in nasal tissue of patients with CRS. Specifically, we were interested in whether antibody‐mediated activation through the classical pathway was a major mechanism for complement activation in patients with CRS. Methods Nasal tissue was obtained from patients with CRS and control subjects. Tissue homogenates were analyzed for complement activation products (ELISA–C5b‐9, C4d, activated C1, and C5a) and major complement‐fixing antibodies (Luminex). Tissue sections were stained for C5b‐9, C4d, and laminin. Antibodies were purified with protein A/G columns from nasal polyps (NP), matching patient serum, and control serum and assayed for basement membrane binding by means of ELISA. Results C5b‐9 levels were significantly increased in NP tissue compared with uncinate tissue (UT) of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and those with chronic rhinosinusitis without nasal polyps (CRSsNP; P < .01). Similarly, C4d levels were increased in NPs compared with UT of patients with CRSwNP, patients with CRSsNP, and control subjects (P < .05). Activated C1 levels were also increased in NP tissue compared with UT of patients with CRSsNP and control subjects (P < .05) and correlated with levels of C5a (P < .01), local immunoglobulins (especially IgM, P < .0001), and anti–double‐stranded DNA IgG (P < .05). Immunofluorescence showed that C5b‐9 and C4d deposition occurred linearly along the epithelial basement membrane. NP tissue extracts had significantly more anti–basement membrane antibodies than sera from patients with CRSwNP and control subjects (P < .0001). Conclusion Levels of C5b‐9, C4d, and activated C1 were significantly increased locally in NP tissue. C5b‐9 and C4d were almost universally deposited linearly along the basement membrane of NP tissue. Furthermore, activated C1 levels were best correlated with local immunoglobulin and C5a levels. Together, these data suggest that the classical pathway plays a major role in complement activation in patients with CRS.

Brand Name and Generic Proton Pump Inhibitor Prescriptions in the United States: Insights from the National Ambulatory Medical Care Survey (2006–2010)

Introduction. Proton pump inhibitors (PPI) are one of the most commonly prescribed medication classes with similar efficacy between brand name and generic PPI formulations. Aims. We determined demographic, clinical, and practice characteristics associated with brand name PPI prescriptions at ambulatory care visits in the United States. Methods. Observational cross sectional analysis using the National Ambulatory Medical Care Survey (NAMCS) of all adult (≥18 yrs of age) ambulatory care visits from 2006 to 2010. PPI prescriptions were identified by using the drug entry code as brand name only or generic available formulations. Descriptive statistics were reported in terms of unweighted patient visits and proportions of encounters with brand name PPI prescriptions. Global chi-square tests were used to compare visits with brand name PPI prescriptions versus generic PPI prescriptions for each measure. Poisson regression was used to determine the incidence rate ratio (IRR) for generic versus brand PPI prescribing. Results. A PPI was prescribed at 269.7 million adult ambulatory visits, based on 9,677 unweighted visits, of which 53% were brand name only prescriptions. In 2006, 76.0% of all PPI prescriptions had a brand name only formulation compared to 31.6% of PPI prescriptions in 2010. Visits by patients aged 25–44 years had the greatest proportion of brand name PPI formulations (57.9%). Academic medical centers and physician-owned practices had the greatest proportion of visits with brand name PPI prescriptions (58.9% and 55.6% of visits with a PPI prescription, resp.). There were no significant differences in terms of median income, patient insurance type, or metropolitan status when comparing the proportion of visits with brand name versus generic PPI prescriptions. Poisson regression results showed that practice ownership type was most strongly associated with the likelihood of receiving a brand name PPI over the entire study period. Compared to HMO visits, patient visits at academic medical centers (IRR 4.2, 95% CI 2.2–8.0), physician-owned practices (IRR 3.9, 95% CI 2.1–7.1), and community health centers (IRR 3.6, 95% CI 1.9–6.6) were all more likely to have brand name PPIs. Conclusion. PPI prescriptions with brand name only formulations are most strongly associated with physician practice type.

Superior turbinate eosinophilia correlates with olfactory deficit in chronic rhinosinusitis patients

To evaluate if molecular markers of eosinophilia in olfactory‐enriched mucosa are associated with olfactory dysfunction.

Evaluating metrics of responsiveness using patient‐reported outcome measures in chronic rhinosinusitis

Responsiveness, or sensitivity to clinical change, is important when selecting patient‐reported outcome measures (PROMs) for research and clinical applications. This study compares responsiveness of PROMs used in chronic rhinosinusitis (CRS) to inform the future development of a highly responsive instrument that accurately portrays CRS patients’ symptom experiences.