Caroline P.E. Price

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.

Oropharyngeal pH Testing Does Not Predict Response to Proton Pump Inhibitor Therapy in Patients with Laryngeal Symptoms

Objectives: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 January 2013 and October 2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-h oropharyngeal pH monitoring, followed by an 8- to 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 the 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 the pre-treatment RSI score. A secondary analysis assessed the relationship between the 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 a greater total percent time below pH of 5.0 (P=0.03), upright percent time below pH of 5.0 (P=0.07), 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).Conclusions: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.

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.

Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis

Background: IgD is an enigmatic antibody isotype best known when coexpressed with IgM on naive B cells. However, increased soluble IgD (sIgD) levels and increased IgD+IgM− B‐cell populations have been described in the human upper respiratory mucosa. Objective: We assessed whether levels of sIgD and IgD+ B cell counts are altered in nasal tissue from patients with chronic rhinosinusitis (CRS). We further characterized IgD+ B‐cell populations and explored clinical and local inflammatory factors associated with tissue sIgD levels. Methods: sIgD levels were measured by means of ELISA in nasal tissues, nasal lavage fluid, sera, and supernatants of dissociated nasal tissues. IgD+ cells were identified by using immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by using real‐time PCR and multiplex immunoassays. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records. Results: sIgD levels and numbers of IgD+ cells were significantly increased in uncinate tissue (UT) of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with that of control subjects (4‐fold, P < .05). IgD+ cells were densely scattered in the periglandular regions of UT from patients with CRSsNP. We also found that IgD+CD19+CD38bright plasmablast numbers were significantly increased in tissues from patients with CRSsNP compared with control tissues (P < .05). Among numerous factors tested, IL‐2 levels were increased in UT from patients with CRSsNP and were positively correlated with tissue IgD levels. Additionally, supernatants of IL‐2–stimulated dissociated tissue from patients with CRSsNP had significantly increased sIgD levels compared with those in IL‐2–stimulated dissociated control tissue ex vivo (P < .05). Tissue from patients with CRS with preoperative antibiotic use or those with pathogenic bacteria showed higher IgD levels compared with tissue from patients without these variables (P < .05). Conclusion: sIgD levels and IgD+CD19+CD38bright plasmablast counts were increased in nasal tissue of patients with CRSsNP. IgD levels were associated with increased IL‐2 levels and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhancement mucosal immunity or inflammation or respond to bacterial infections in patients with CRS, especially CRSsNP.

A prospective analysis evaluating tissue biopsy location and its clinical relevance in chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high propensity for recurrence. Studies suggest that eosinophilia influences disease severity and surgical outcomes, but the selection of sinonasal site for measuring eosinophilia has not been examined. The aim of this study was to investigate how region‐specific tissue eosinophilia affects radiographic severity, comorbidity prevalence, and polyp recurrence risk following sinus surgery.

Asthma onset pattern and patient outcomes in a chronic rhinosinusitis population: Asthma onset and patient characteristics in CRS

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.

Mo1115 Salivary Pepsin Concentrations Are Higher for Patients With Reflux Associated Laryngeal Symptoms: A Prospective Pilot Study

Background: It has been demonstrated, using 24h pH-impedance monitoring (MII-pH), that NERD patients not responding to PPIs are characterized, respect to responders, by an increased overall number of refluxes and by enhanced sensitivity to mixed and proximal reflux episodes. It has been also shown that non-responders swallow more air at mealtime than responder patients. Aim: To explore the relationship between swallowing and reflux pattern in 24 hours in NERD patients responding or not to PPIs. Methods: MII-pH was performed, after a washout from PPIs, in 41 NERD non-responders and in 70 responders to double dose of PPIs, presenting with typical symptoms, following esophageal manometry. All patients filled out a questionnaire with symptom score. Acid exposure time (AET) and Symptom Association Probability (SAP) index were calculated. For each patients, swallows were evaluated during the entire length of MII-pH study, excluding meal period. Air swallowing was also assessed. Due to the high frequency of artifacts, the meal period was excluded from the analysis. Patients were instructed to have 3 meals and 4 beverages at fixed times. Results: 11 non responders (4 with ineffective esophageal motility, 7 with normal AET and SAP) and 20 responders (9 with ineffective esophageal motility, 11 with normal AET and SAP) were excluded thus 30 non-responders and 50 responders were studied. Nine nonresponders and 29 responders showed a pathological AET. Non responder patients were characterized, compared to responders, by a higher overall number of reflux episodes (median, 25th-75th percentile; 67, 43-94 vs 42, 31-65, p<0.01). The proportion of weakly (41% vs 39%), mixed (46% vs 44%) and proximal (53% vs 47%) reflux episodes did not differ between non responders and responders. During MII-pH, non responders swallowed more frequently than responders (mean±SD, 445±112 vs 381±89, p<0.05). The swallow rate per hour was 19±4.9/h in non responders and 16.6±3.9/h in responders. In both non responders and responders the swallowing frequency significantly decreased during sleep (13.3±1.2/h and 11.4±0.8/h, p<0.01). Swallows were followed by reflux episodes after 56.5±18.4sec. in non responders and 75±22.8 in responders (p<0.01). The frequency of air swallows were comparable between the two groups (56% vs 49%). Conclusions: Non responder NERD patients are characterized by an increased frequency of swallows during 24 hours. This finding may explain the increased number of reflux episodes observed in non responder patients, and further support the role of mucosal sensitization in this subgroup of patients.