Relationship between socioeconomic status, exposure to airborne pollutants, and chronic rhinosinusitis disease severity.

BACKGROUND: Air pollution directly interacts with airway mucosa, yet little is known about how pollutants affect upper airway inflammation. Studies have shown increased incidence of chronic rhinosinusitis (CRS), rhinitis, and asthma in areas with higher traffic pollution, and these neighborhoods are often associated with lower socioeconomic status (SES). The Area Deprivation Index (ADI) assesses neighborhood-level SES by zip code. The purpose of this study was to assess the relationship between SES and exposure to inhaled pollutants and CRS disease severity. METHODS: CRS patients with and without nasal polyps (CRSwNP and CRSsNP, respectively) were identified (total patients = 234; CRSwNP patients = 138; CRSsNP patients = 96). Pollutant concentrations, including particulate matter 2.5 (PM2.5 ), black carbon (BC), and nitrogen dioxide (NO2 ), were measured at 70 sites within the defined countywide sites and used to estimate patient exposures. SES was measured by ADI state deciles. Disease severity metrics included the modified Lund-Mackay score (LMS), the need for systemic steroids, and functional endoscopic sinus surgery (FESS). Associations were analyzed and identified using linear, logistic, and Poisson multivariable regression. RESULTS: The distribution of CRSsNP and CRSwNP patients across ADI state deciles was similar. ADI, however, was a predictor of exposure to airborne pollutants (PM2.5 , BC, and NO2 ) with a 1.39%, 2.39%, and 2.49% increase in PM2.5 , BC, and NO2 per increasing decile increment (p < 0.0001), respectively, which demonstrated a direct correlation between deprived neighborhoods and higher levels of exposure to PM2.5 , BC, and NO2 with an increase in pollutant levels per increase in ADI decile. Furthermore, ADI was a predictor for increased steroid treatment. CONCLUSION: Lower SES predicted higher exposure to air pollution and increased disease severity in patients with CRS as demonstrated by the increased need for steroid treatment.

Association of air pollutants, airborne occupational exposures, and chronic rhinosinusitis disease severity.

BACKGROUND: Previous work has shown that chronic rhinosinusitis (CRS) severity may be associated with particulate matter 2.5 (PM2.5 ) and black carbon (BC) in CRS patients without nasal polyps (CRSsNP). Data regarding occupational exposures, however, are lacking. We assessed the impact of PM2.5 , BC, as well as occupational airborne exposure on CRS disease severity. METHODS: Patients with CRS with nasal polyps (CRSwNP), CRSsNP, and aspirin-exacerbated respiratory disease (AERD) were identified from an institutionwide database. Spatial modeling from 37 pollutant monitoring sites in Allegheny County was used to estimate exposures. Patient occupations using the 2010 Standard Occupation Classification (SOC10) and airborne occupation exposures to vapors, gases, dusts, fumes, fibers and mists (VGDFFiM) or diesel fumes were recorded. Disease severity was measured by modified Lund-Mackay score (LMS), systemic corticosteroid therapy, and incidence of functional endoscopic sinus surgery (FESS). RESULTS: Two hundred thirty-four patients were included (CRSwNP, n = 113; CRSsNP, n = 96; AERD, n = 25). The prevalence of AERD among those with CRSwNP was 18%. Patients exposed to VGDFFiM or diesel fumes required higher steroid doses vs nonexposed patients (p = 0.015 and p = 0.03, respectively); patients with VGDFFiM levels >5% were more likely to undergo FESS vs nonexposed patients (p = 0.0378). There was no difference in PM2.5 and BC with regard to disease severity and FESS between CRSwNP, CRSsNP, and AERD patients. Steroid use was significantly higher in CRSwNP and AERD vs CRSsNP (p = 0.001). LMS was significantly higher in AERD as compared with CRSwNP and CRSsNP (p = 0.001). CONCLUSION: Occupational airborne exposure to VGDFFiM correlated with increased prevalence of FESS and need for corticosteroids in CRS patients. There was no difference in PM2.5 and BC levels and disease severity outcome measures between CRS subtypes in this subset.

15-Lipoxygenase 1 in nasal polyps promotes CCL26/eotaxin 3 expression through extracellular signal-regulated kinase activation.

BACKGROUND: 15-Lipoxygenase 1 (15LO1) is expressed in airway epithelial cells in patients with type 2-high asthma in association with eosinophilia. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also associated with type 2 inflammation and eosinophilia. CCL26/eotaxin 3 has been reported to be regulated by 15LO1 in lower airway epithelial cells. However, its relation to 15LO1 in patients with CRSwNP or mechanisms for its activation are unclear. OBJECTIVE: We sought to evaluate 15LO1 and CCL26 expression in nasal epithelial cells (NECs) from patients with CRSwNP and healthy control subjects (HCs) and determine whether 15LO1 regulates CCL26 in NECs through extracellular signal-regulated kinase (ERK) activation. METHODS: 15LO1, CCL26, and phosphorylated ERK were evaluated in NECs from patients with CRSwNP and HCs. 15LO1/CCL26 and CCL26/cytokeratin 5 were colocalized by means of immunofluorescence. IL-13-stimulated NECs were cultured at an air-liquid interface with or without 15-lipoxygenase 1 gene (ALOX15) Dicer-substrate short interfering RNAs (DsiRNA) transfection, a specific 15LO1 enzymatic inhibitor, and 2 ERK inhibitors. Expression of 15LO1 and CCL26 mRNA and protein was analyzed by using quantitative RT-PCR, Western blotting, and ELISA. RESULTS: 15LO1 expression was increased in nasal polyp (NP) epithelial cells compared with middle turbinate epithelial cells from patients with CRSwNP and HCs. 15LO1 expression correlated with CCL26 expression and colocalized with CCL26 expression in basal cells of the middle turbinate and NPs from patients with CRSwNP. In primary NECs in vitro, IL-13 induced 15LO1 and CCL26 expression. 15LO1 knockdown and inhibition decreased IL-13-induced ERK phosphorylation and CCL26 expression. ERK inhibition (alone) similarly decreased IL-13-induced CCL26. Phosphorylated ERK expression was increased in NECs from CRSwNP subjects and positively correlated with both 15LO1 and CCL26 expression. CONCLUSIONS: 15LO1 expression is increased in NP epithelial cells and contributes to CCL26 expression through ERK activation. 15LO1 could be considered a novel therapeutic target for CRSwNP.

Clinical predictors of cystic fibrosis chronic rhinosinusitis severity.

BACKGROUND: Chronic rhinosinusitis (CRS) is a significant manifestation of cystic fibrosis (CF) with wide-ranging symptom and disease severity. The goal of the study was to determine clinical variables that correlate with outcome measures of disease severity. METHODS: A prospective, longitudinal, observational study of 33 adults with symptomatic CRS treated in a CF-focused otolaryngology clinic was performed. Symptom severity, the presence of rhinosinusitis exacerbations, and endoscopic appearance were assessed, and regression analysis was used to determine clinical predictors of disease outcome. RESULTS: Thirty-three adults with CF-CRS were included in the study and followed for a mean of 15 months. Rhinosinusitis exacerbations occurred in 61% of participants during the study, and female sex increased the odds of presenting with an exacerbation visit. Sinus disease exacerbations were associated with an odds ratio of 2.07 for presenting with a pulmonary exacerbation at the next visit. CF-related diabetes was found to be associated with worse symptoms and endoscopic appearance. Infection with Staphylococcus aureus predicted worsening of symptoms, whereas infections with Pseudomonas aeruginosa improved over time. Allergic rhinitis was associated with worse endoscopic appearance, and nasal steroid use was associated with improved endoscopic appearance. CONCLUSION: Sex, CF-related diabetes, sinonasal infection status, allergic rhinitis, and nasal steroid use may all modulate severity of CF-CRS in adults. Sinusitis exacerbation may be a precursor to pulmonary exacerbation.

Comparative effectiveness of allergy testing method in driving immunotherapy outcomes.

BACKGROUND: Skin-prick testing (SPT), in vitro testing (IVT), and intradermal-dilutional testing (IDT) are methods to detect patient sensitivities to specific allergens and direct immunotherapy dosing. We used objective and subjective measures of improvement to compare outcomes based on test method. METHODS: Patients underwent 1 of 3 protocols: SPT, screening SPT followed by IDT, or IVT. We used institution billing data to do a cost analysis of these tests. The time to maintenance (TTM) therapy was analyzed and patients were stratified into high and low reactors. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used to quantify symptoms pre-maintenance and post-maintenance. RESULTS: Of 177 patients (SPT, n = 40; IVT, n = 91; IDT, n = 46), 115 (SPT, n = 35; IVT, n = 39; IDT, n = 41) were high reactors. Out of 90 patients (SPT, n = 17; IVT, n = 37; IDT, n = 36) reaching maintenance, 58 were high reactors (SPT, n = 15; IVT, n = 12; IDT, n = 31). Overall, SPT, IVT, and IDT median TTM were 542, 329, and 578.5 days, respectively. IDT TTM was shorter compared to IVT overall and in high reactors (hazard ratio [HR] = 1.91, p = 0.02; HR = 2.12, p = 0.03), but was not significant compared to SPT high reactors (p = 0.33). The IDT cost was $62.66, translating to an incremental cost-effectiveness ratio of $0.23 per day of shortened TTM. Median RQLQ change for the SPT, IVT, and IDT groups was 6.5, 1, and 1.5, respectively, but was not significant (p = 0.60). CONCLUSION: IDT reached maintenance immunotherapy quicker than IVT but there was no difference compared to SPT. TTM did not correlate with improvements in patient symptoms between testing methods. This study represents a novel comparison of outcomes based on initial allergy testing method.

Air pollutants may be environmental risk factors in chronic rhinosinusitis disease progression.

BACKGROUND: Little is known about the role of environmental exposures in the pathophysiology of chronic rhinosinusitis (CRS). In this study, we measured the impact of air pollutants (particulate matter 2.5 [PM2.5 ] and black carbon [BC]) on CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP). METHODS: Spatial modeling from pollutant monitoring sites was used to estimate exposures surrounding residences for patients meeting inclusion criteria (total patients, n = 234; CRSsNP, n = 96; CRSwNP, n = 138). Disease severity outcome measures included modified Lund-Mackay score (LMS), systemic steroids, number of functional endoscopic sinus surgeries (FESS), and 22-item Sino-Nasal Outcome Test (SNOT-22) score. PM2.5 and BC exposures were correlated with outcome measures. RESULTS: Mean PM2.5 and BC findings were not significantly different between CRSwNP and CRSsNP patients or patients with and without asthma. Among those with CRSsNP, PM2.5 was significantly associated with undergoing FESS. For each unit increase in PM2.5 , there was a 1.89-fold increased risk in the proportion of CRSsNP patients who required further surgery (p = 0.015). This association was not identified in CRSwNP patients (p = 0.445). BC was also significantly associated with SNOT-22 score in the CRSsNP group. For each 0.1-unit increase in BC, there was a 7.97-unit increase in SNOT-22 (p = 0.008). A similar, although not significant, increase in SNOT-22 was found with increasing BC in the CRSwNP group (p = 0.728). CONCLUSION: Air pollutants correlate with CRS symptom severity that may be influenced by exposure levels, with a more pronounced impact on CRSsNP patients. This study is the first to demonstrate the possible role of inhalant pollutants in CRS phenotypes, addressing a critical knowledge gap in environmental risk factors for disease progression.

The association of air pollutants and allergic and nonallergic rhinitis in chronic rhinosinusitis.

BACKGROUND: There has been little investigation regarding air quality and rhinitis in the pathophysiology of upper airway disease. In this study, we assessed the impact of inhalant pollutants (particulate matter 2.5 [PM2.5 ] and black carbon [BC]) on allergic rhinitis and chronic rhinosinusitis (CRS) disease severity. METHODS: CRS patients with nasal polyps (CRSwNP) and without polyps (CRSsNP) were identified. Spatial modeling from pollutant monitoring sites was used to estimate exposures for patients meeting the inclusion criteria (total, n = 125; CRSsNP, n = 67; CRSsNP, n = 58). Skin-prick, intradermal dilutional, and in-vitro testing methods were utilized to determine aeroallergen sensitization. Disease severity indicators were measured by modified Lund-Mackay score (LMS), the 22-item Sino-Nasal Outcome Test (SNOT-22), systemic steroid therapy, and number of functional endoscopic sinus surgeries (FESS). RESULTS: Thirty-six percent (n = 45) of patients who described rhinitis symptoms demonstrated no reactivity to aeroallergen testing. Sixty-four percent (n = 80) tested positive for at least 1 allergen, with no differences found between CRSsNP and CRSwNP (62.1% vs 67.2%). There were significant differences in air pollutants between patients testing negative and positive for allergies (nonallergic vs allergic: PM2.5 , 11.32 vs 11.07 µg/m3 , p = 0.030; BC, 0.81 vs 0.76 absorbance, p =0.044). Nonallergic CRSwNP demonstrated higher PM2.5 compared with allergic counterparts (11.48 vs 11.09 µg/m3 , p = 0.032). A similar pattern was observed with BC (0.82 vs 0.75 absorbance, p = 0.017). In CRSsNP, BC correlated significantly with SNOT-22 (r = 0.55, p = 0.042). CONCLUSION: Our results suggest that small inhalant pollutants may contribute to nonallergic symptomatology in patients with and without nasal polyps. Regardless of allergy status, BC may play a role in CRS symptom severity.

A systematic review of sinonasal oncocytomas and oncocytic carcinomas: Diagnosis, management, and technical considerations.

BACKGROUND: Oncocytomas and oncocytic carcinomas are rare tumors of the sinonasal cavity with the propensity for local invasion. This report and systematic review details a case of a nasal oncocytoma involving the lacrimal sac and provides an update of the current literature. METHODS: A systematic literature review was performed using PubMed and Ovid databases. The data obtained from published articles with sinonasal oncocytoma/oncocytic carcinoma as the primary diagnosis included patient demographics, presentation, radiographic and histologic findings, management, and recurrence rates. RESULTS: Twenty cases were identified. The most common symptoms were epistaxis (n = 11) and nasal obstruction (n = 11). Involvement of the nasal cavity was most common (n = 17), followed by the paranasal sinuses (n = 13) and nasolacrimal apparatus (n = 4). Recurrence occurred in 55% of cases. Recurrence was associated with invasion or infiltration found on histology or the presence of both invasion/infiltration and mitotic figures/pleomorphism (p < 0.05), with no significant relationship between recurrence and age at diagnosis (p = 0.42), sex (p = 0.65), and location of tumor (p = 0.14). The authors present the case of a 73-year-old woman with a 5-month history of worsening epistaxis and biopsy-proven oncocytoma. Complete surgical resection of the tumor using combined endonasal endoscopic and anterior orbitotomy approach is described. CONCLUSION: Oncocytomas and oncocytic carcinomas are rare tumors of the sinonasal cavity with a high rate of local recurrence and orbital involvement. Surgical resection is the treatment of choice and complete resection can be achieved with an endoscopic endonasal approach.

Predictive factors in patients undergoing endoscopic sinus surgery for odontogenic sinusitis.

BACKGROUND: Odontogenic sinusitis (OS) presents a therapeutic dilemma. Evidence is lacking whether dental treatment alone is sufficient or whether patients will eventually require endoscopic sinus surgery (ESS). Our aim was to identify predictors of OS patients undergoing ESS. METHODS: Retrospective review performed of OS patients (n = 43) analyzing multiple factors including age, sex, symptoms, prior dental procedures, treatment, diabetes, immunosuppression, smoking history, retained dental hardware, oral-antral fistula (OAF), and Lund-Mackay scores (LMSs). Descriptive statistics, Wilcoxon rank sum, and logistic regression analyses were performed. RESULTS: Common presenting symptoms included facial pressure, discolored nasal drainage, and foul smell/taste. Half of patients presented either after a recent dental procedure or with dental complaints. Forty-eight percent required ESS after failing medical and dental therapy alone. Total LMS was significantly higher in the group undergoing ESS (8.3 vs 3.7; p = 0.0003). Multivariate analysis showed 2 significant predictors of undergoing ESS: (1) OMC involvement (OR 37.3, p = 0.003) and prior dental procedure (OR 7.4, p = 0.03). All patients with OAF or retained dental hardware required ESS. CONCLUSION: Forty-eight percent of patients who presented with OS underwent ESS for symptom control and prevention of complications. Patients who underwent ESS had significantly higher total LMS than those who did not. In multivariate analysis, prior dental procedures and OMC involvement significantly increased the likelihood of requiring ESS.

Pharmacotherapy for the treatment of asthma: current treatment options and future directions.

BACKGROUND: Asthma is a prevalent disease characterized by chronic inflammatory changes of the airway and marked by airway hyperresponsiveness, edema, and excess mucus production. Management of the disease has focused upon reversing the early airway changes and limiting the late effects of airway remodeling. Several classes of medications are available for the effective treatment and long-term control of asthma and novel therapeutic options are in development that hold promise in improving patient outcome. METHODS: A review of updated guidelines and current literature was conducted to identify available pharmacologic treatments of asthma and determine future directions in development of novel therapeutic options. RESULTS: Inhaled corticosteroids are the most effective medications in long-term asthma control with adjunct medications such as ß2-agonists, which can provide symptomatic relief. Other classes of asthma control medications including anticholinergics, cromolyns, and leukotriene receptor modifiers can also be used to develop an effective management strategy based on asthma severity. CONCLUSION: Several classes of medications are available for the effective management of asthma. Inhaled corticosteroids play a central role in control of inflammation and several other adjuncts are available to tailor therapy to the patient's symptoms. New therapeutic options that target downstream inflammatory mediators can provide increased efficacy while limiting side effects.

Practical clinical approaches to the allergic rhinitis patient.

BACKGROUND: Numerous treatment strategies are available for the treatment of allergic rhinitis (AR), including environmental controls, pharmacotherapy, immunotherapy, and surgery in appropriately selected patients. A stepwise algorithmic approach based on disease severity and persistence of symptoms is often advocated to effectively manage patients with AR. METHODS: A review is provided of current evidence and guidelines for the management of AR. Practical clinical strategies to improve patient adherence to therapy and outcome are described. RESULTS: Algorithms to manage AR are based on the severity and persistence of disease. A tailored strategy geared toward addressing symptoms that are most troublesome to the patient is beneficial, as is the assessment of comorbid conditions such as rhinosinusitis, asthma, and laryngopharyngeal reflux. Allergen-specific immunotherapy (AIT) is an underused treatment modality and patients with persistent AR should be considered candidates for desensitization, if appropriate. Assessment of patient outcome is important and the use of validated symptom surveys can provide an objective measure of quality of life. CONCLUSION: A large armamentarium of treatment options is available to the otolaryngologist treating the patient with AR. A step-wise and tailored approach with equal attention dedicated to patient education and assessment of patient outcome can be helpful to improve efficacy of treatment.

Clinical and pathologic characteristics of intranasal abuse of combined opioid-acetaminophen medications.

BACKGROUND: The nonmedical abuse of prescription opioids via intranasal administration is a growing problem. The objective of this study is to investigate of the typical presentation of intranasal opioid-acetaminophen abuse and outline optimal therapy. METHODS: This study was a retrospective chart review. Patients with intranasal pathology from inhalation of combined opioid-acetaminophen medications (COAMs) from 3 academic otolaryngology practices in western Pennsylvania from January 2012 to October 2012 were included in the review. RESULTS: Seven adults ranging in age from 23 to 46 years were identified with nasal complaints from the intranasal inhalation of COAMs. All patients presented with nasal pain and were found to have fibrinous necrotic nasal mucosa involving the posterior nasal cavity and nasopharynx. Of the 7 patients, 6 (85.7%) presented with a septal perforation. Pathology and culture revealed fungus in 85.7% of the patients; however, no invasive fungal disease was noted in any of the specimens. Patients did not improve with either systemic or topical antifungal therapy. Polarizable material characteristic of talc used as a tablet binder was present in the histopathology of 4 of 7 (57.1%) patients. Patients who abstained from intranasal drug use along with serial debridement demonstrated the greatest improvement. CONCLUSION: Intranasal COAM abuse causes nasal pain, tissue necrosis with potential septal and palatal perforation, and noninvasive fungal colonization. Antifungal therapy was of no benefit in the current series of patients. Current therapy should focus on recognition of the etiology of patients' pathology and encourage abstinence from intranasal use of these drugs along with serial debridements.

Defining quality metrics and improving safety and outcome in allergy care.

BACKGROUND: The delivery of allergy immunotherapy in the otolaryngology office is variable and lacks standardization. Quality metrics encompasses the measurement of factors associated with good patient-centered care. These factors have yet to be defined in the delivery of allergy immunotherapy. We developed and applied quality metrics to 6 allergy practices affiliated with an academic otolaryngic allergy center. METHODS: This work was conducted at a tertiary academic center providing care to over 1500 patients. We evaluated methods and variability between 6 sites. Tracking of errors and anaphylaxis was initiated across all sites. A nationwide survey of academic and private allergists was used to collect data on current practice and use of quality metrics. RESULTS: The most common types of errors recorded were patient identification errors (n = 4), followed by vial mixing errors (n = 3), and dosing errors (n = 2). There were 7 episodes of anaphylaxis of which 2 were secondary to dosing errors for a rate of 0.01% or 1 in every 10,000 injection visits/year. Site visits showed that 86% of key safety measures were followed. Analysis of nationwide survey responses revealed that quality metrics are still not well defined by either medical or otolaryngic allergy practices. Academic practices were statistically more likely to use quality metrics (p = 0.021) and perform systems reviews and audits in comparison to private practices (p = 0.005). CONCLUSION: Quality metrics in allergy delivery can help improve safety and quality care. These metrics need to be further defined by otolaryngic allergists in the changing health care environment.