Background The objective of this study was to describe the first US-based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis (CRS) in a general population sample. Methods A CRS symptom questionnaire was mailed to 23,700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups. Results We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50–59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Co-morbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms. Conclusions CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.

Background & Aims It has been a challenge to confirm the association between laryngeal symptoms and physiologic reflux disease. We examined the ability of oropharyngeal pH tests (with the Restech Dx-pH system) and salivary pepsin tests (with Peptest) to discriminate between asymptomatic volunteers (controls) and subjects with a combination of laryngeal and reflux symptoms (laryngeal±reflux). Methods We performed a physician-blinded prospective cohort study of 59 subjects at a single academic institution. Adult volunteers were recruited and separated into 3 groups based on GerdQ and reflux symptom index scores: controls (n=20), laryngeal symptoms (n=20), or laryngeal+reflux symptoms (n=19). Subjects underwent laryngoscopy and oropharyngeal pH tests and submitted saliva samples for analysis of pepsin concentration. Primary outcomes included abnormal acid exposure and composite (RYAN) score for oropharyngeal pH tests and abnormal mean salivary pepsin concentration based on normative data. Results Complete oropharyngeal pH data were available from 53 subjects and complete salivary pepsin data from 35 subjects. We did not observe any significant differences between groups in percent time spent below pH 4.0, 5.0, 5.5, 6.0 or RYAN scores; or percent of subjects with positive results from tests for salivary pepsin (53% vs 40% vs 75%; P=.50, respectively). The laryngeal+reflux group had a significantly higher estimated mean concentration of salivary pepsin (117.9±147.4ng/mL) than the control group (32.4±41.9ng/mL) or laryngeal symptom group (7.5±11.2ng/mL) (P=.01 and P=.04, respectively). Conclusions Using current normative thresholds, oropharyngeal pH testing and salivary pepsin analysis are not able to distinguish between healthy volunteers and subjects with a combination of laryngeal and reflux symptoms.

Objective To evaluate if molecular markers of eosinophilia in olfactory enriched mucosa are associated with olfactory dysfunction. Study Design Cross-sectional study of tissue biopsies from 99 patients, and a further 30 patients who underwent prospective olfactory testing prior to sinonasal procedures. Methods Tissue biopsies were processed for analysis of inflammatory markers using qRT-PCR. Ipsilateral olfactory performance was assessed using the Sniffin Sticks threshold component and the UPSIT and age-adjusted data was correlated with inflammatory marker expression and clinical measures of obstruction from CT and endoscopy. Results Gene expression of the eosinophil marker CLC (Charcot Leyden crystal protein) was elevated in superior turbinate (ST) tissue in CRS with nasal polyps (CRSwNP) compared to ST and inferior turbinate (IT) tissue in CRS without nasal polyps (CRSsNP) and control patients (all p < 0.001 respectively). CLC in ST tissue was correlated with IL-5 and eotaxin-1 expression (all p<0.001; r = 0.65 and 0.49 respectively). CLC expression was strongly correlated with eosinophilic cationic protein levels (p<0.001; r=0.-76) and ST CLC expression was inversely related to olfactory threshold (p = 0.002, r = −0.57) and discrimination scores (p = 0.05, r = −0.42). In multiple linear regression of CLC gene expression, polyp status, radiographic and endoscopic findings with olfactory threshold, CLC was the only significantly correlated variable (p<0.05). Conclusions Markers of eosinophils are elevated in the ST of patients with CRSwNP and correlate with olfactory loss. These findings support the hypothesis that olfactory dysfunction in CRS correlates local eosinophil influx into the olfactory cleft.

Background Chronic rhinosinusitis (CRS) is a common condition encountered in primary care medicine and is estimated to affect 12.5% of the United States population. This study aims to compare methods of assessing health utility in CRS Methods A cross-sectional sample of CRS patients (n=137) were interviewed using direct health utility assessment measures: the visual analog scale (VAS), time trade-off (TTO), and standard gamble (SG). General quality of life (QOL) scores were obtained via the 36-item Short Form Health Survey (SF-36) and converted to SF-6D health utility values using a Bayesian algorithm. Disease specific quality of life was measured with the SNOT-22. A selected subgroup of patients (n=51) not initiating surgery or new treatment for CRS were re-interviewed within three weeks. Results The mean (±SD) health utilities were VAS 0.69(±0.19), TTO 0.80(±0.27), SG 0.93(±0.11), SF-6D 0.72(±0.12) and differed significantly (p<0.001). Only VAS scores differed based on disease state classification or the presence of nasal polyposis. Correlations between methods of determining health utility were weak, but significant. VAS, TTO and SF-6D scores were significantly associated with SNOT-22 (p<0.001 for all), however SG and SNOT-22 were poorly correlated (Spearman correlation=-0.33). The test-retest reliability of TTO (Spearman correlation=0.71) and SG (0.73) was strong. Conclusions CRS patients show significant impairment in quality of life, with health utility values similar to those of patients with AIDS or intermittent claudication using similar methods. The method of ascertainment significantly affects measured health utility, but the degree of impairment warrants improved recognition and appropriate treatment of the condition.

Background Chronic rhinosinusitis (CRS) is strongly associated with comorbid asthma. This study compares early-onset and late-onset asthma in a CRS population using patient-reported and clinical characteristics. Methods At enrollment into a clinical registry, CRS patients completed the 22-item Sino-Nasal Outcome Test (SNOT-22), Asthma Control Test (ACT), mini-Asthma Quality of Life Questionnaire (miniAQLQ), the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29), and medication use questionnaires. Patients also reported comorbid asthma and age at first asthma diagnosis. Early-onset (<18 years) and late-onset (>18 years) asthma groups were defined. Analysis of variance (ANOVA), chi-square, and Kruskal-Wallis tests were used to compare patient responses. Results A total of 199 non-asthmatic (56.1%), 71 early-onset asthmatic (20.0%), and 85 late-onset asthmatic (23.9%) CRS patients completed the survey. Body mass index (BMI) was significantly higher in late-onset asthmatic (p = 0.046) while age, gender, race, and smoking history did not differ with time of asthma onset. SNOT-22, ACT, and miniAQLQ were not different between asthma groups, but late-onset asthmatics had significantly lower physical function than non-asthmatics (p = 0.008). Compared to non-asthmatics, late-onset asthmatics showed increased rates of nasal polyps (p < 0.001), higher Lund-Mackay scores (p = 0.005), and had received more oral steroid courses (p < 0.001) and endoscopic surgeries (p = 0.008) for CRS management. Late-onset asthmatics compared to early-onset asthmatics showed increased nasal polyposis (p =0.011) and oral steroid courses for CRS (p = 0.003). Conclusion While CRS-specific and asthma-specific patient-reported outcome measures (PROMs) were not significantly different among groups, CRS patients with late-onset asthma had poorer physical function, more frequent nasal polyposis, and required increased treatment for CRS. Late-onset asthma may predict more severe disease in CRS.

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Introduction Predicting response to proton-pump inhibitor (PPI) therapy in patients with laryngeal symptoms is challenging. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. In this study, we aimed to investigate the prognostic potential of oropharyngeal pH monitoring to predict responsiveness to PPI therapy in patients with laryngeal symptoms. Methods We conducted a physician blinded prospective cohort study at a single academic institution between 1/2013–10/2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-hour oropharyngeal pH monitoring, followed by an 8–12 week trial of omeprazole 40 mg daily. Prior to, and following PPI therapy, patients completed various symptom questionnaires. The primary outcome was the association between PPI response and oropharyngeal pH metrics. PPI response was separated into three subgroups based on post-treatment RSI score and % RSI response: Non-response = RSI ≥ 13; Partial response = post-treatment RSI < 13 and change in RSI < 50%; and Complete response = post-treatment RSI < 13 and change in RSI ≥ 50%. The primary analysis utilized a multinomial logistic regression controlling for pre-treatment RSI score. A secondary analysis assessed the relationship between change in RSI (post-pre) and oropharyngeal pH metrics via ordinary least square regression. Results Thirty-four patients completed the study and were included in final analysis. Symptom response to PPI therapy was as follows: 50% no response, 15% partial-response and 35% complete-response. Non-responders had a higher pre-treatment RSI (P < 0.01). There were no significant differences in oropharyngeal acid exposure (below pH of 4.0, 5.0, 5.5, 6.0 and RYAN scores) between responder types. The secondary analysis noted a trend between lower PPI response and greater total percent time below pH of 5.0 (P = 0.03), upright percent time below pH of 5.0 (p = .07) and RYAN supine (corrected) (P = 0.03), as well as an association between PPI response and greater decreases in the Anxiety Sensitivity Inventory (P < 0.01), Brief Symptom Inventory-18 (P < 0.01), and Negative Affect Scale (P < 0.01). Discussion Oropharyngeal pH testing did not predict laryngeal symptom response to PPI therapy. Contrary to hypothesis, our study signaled that the degree of oropharyngeal acid exposure is inversely related to PPI response. In addition, reduction in negative affect and psychological distress parallels PPI response.

Background 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. Methods Adult CRS patients initiating medical therapy (MT: n=143) or undergoing endoscopic sinus surgery after failing MT (ESS: n=123) completed the Sino-Nasal Outcome Test (SNOT)-22, European Position Statement on Rhinosinusitis (EPOS) visual analog scale (VAS), and Patient-Reported Outcomes Measurement Information System (PROMIS)-29 at baseline and 3 months following treatment. Cohen’s d and paired t statistics were used to evaluate the responsiveness of each measure. Results Respectively, 52 (36.4%) subjects and 42 (34.1%) subjects in the MT and ESS groups completed baseline and 3-month questionnaires. Subjects with and without 3-month data were similar with respect to baseline demographics, VAS scores, and SNOT-22 scores (p>0.05). In MT patients, CRS-specific measures like VAS (d=−0.58, p<.01; t=−1.81, p>.05) and SNOT-22 scores (d=−0.70, p<.01; t=−3.29, p<.05) were more responsive than PROMIS-29 general health domains (p>0.05 for Cohen’s d). In ESS patients, VAS (d=−1.97; t=−9.63, both p<.01) and SNOT-22 scores (d=−1.56; t=−9.99, both p<.01) were similarly more responsive although changes in PROMIS-29 Fatigue (d=−0.82, p=.01; t=−4.63, p<.01); Sleep Disturbance (d=−0.83; t=−3.77, both p<.01); and Pain Intensity (d=−1.0; t=−5.67, both p<.01) domains were significant. All 22 individual SNOT-22 items differed significantly following surgery whereas only 8 items were consistently responsive after MT. Conclusions For both MT and ESS patients, CRS-specific PROMs are more responsive to post-treatment clinical changes than general health measures. Still, the SNOT-22 contains items that likely decrease its overall responsiveness. Our findings also indicate that existing PROMs show greater response to ESS than MT.