Steven G. Brooks

T2R38 genotype is correlated with sinonasal quality of life in homozygous ΔF508 cystic fibrosis patients

Chronic rhinosinusitis (CRS) is very prevalent in the cystic fibrosis (CF) patient population, and leads to high morbidity and markedly decreased quality of life (QOL). Identification of genetic markers that contribute to CRS symptoms in these patients can allow for risk stratification and tailoring of medical and surgical treatments. T2R38 is a bitter taste receptor expressed in the sinonasal tract, and nonfunctional alleles of this receptor have been implicated in treatment‐refractory CRS in non‐CF patients. The purpose of this study is to investigate the significance of T2R38 genotype in the variability of sinonasal QOL and CRS disease severity in a sample of CF patients.

Denatonium-induced sinonasal bacterial killing may play a role in chronic rhinosinusitis outcomes: Denatonium-responsiveness and CRS outcomes

Sinonasal bitter taste receptors (T2Rs) contribute to upper airway innate immunity and correlate with chronic rhinosinusitis (CRS) clinical outcomes. A subset of T2Rs expressed on sinonasal solitary chemosensory cells (SCCs) are activated by denatonium, resulting in a calcium‐mediated secretion of bactericidal antimicrobial peptides (AMPs) in neighboring ciliated epithelial cells. We hypothesized that there is patient variability in the amount of bacterial killing induced by different concentrations of denatonium and that the differences correlate with CRS clinical outcomes.

The Role of Quinine-Responsive Taste Receptor Family 2 in Airway Immune Defense and Chronic Rhinosinusitis

Background Bitter (T2R) and sweet (T1R) taste receptors in the airway are important in innate immune defense, and variations in taste receptor functionality in one T2R (T2R38) correlate with disease status and disease severity in chronic rhinosinusitis (CRS). Quinine is a bitter compound that is an agonist for several T2Rs also expressed on sinonasal cells, but not for T2R38. Because of this property, quinine may stimulate innate immune defense mechanisms in the airway, and functional differences in quinine perception may be reflective of disease status in CRS. Methods Demographic and taste intensity data were collected prospectively from CRS patients and non-CRS control subjects. Sinonasal tissue from patients undergoing rhinologic surgery was also collected and grown at an air–liquid interface (ALI). Nitric oxide (NO) production and dynamic regulation of ciliary beat frequency in response to quinine stimulation were assessed in vitro. Results Quinine reliably increased ciliary beat frequency and NO production in ALI cultures in a manner consistent with T2R activation (p < 0.01). Quinine taste intensity rating was performed in 328 CRS patients and 287 control subjects demonstrating that CRS with nasal polyps (CRSwNP) patients rated quinine as significantly less intense than did control subjects. Conclusion Quinine stimulates airway innate immune defenses by increasing ciliary beat frequency and stimulating NO production in a manner fitting with T2R activation. Patient variability in quinine sensitivity is observed in taste intensity ratings, and gustatory quinine “insensitivity” is associated with CRSwNP status. Thus, taste tests for quinine may be a biomarker for CRSwNP, and topical quinine has therapeutic potential as a stimulant of innate defenses.

Association between the CDHR3 rs6967330 risk allele and chronic rhinosinusitis

A retrospective, multi-center study of adults with and without chronic rhinosinusitis (CRS) identifies a significant association between rs6967330 in the viral receptor CDHR3 – known to be associated with wheezing and asthma in children – and the development of CRS.

The nasofrontal beak: A consistent landmark for superior septectomy during Draf III drill out.

Introduction Cerebrospinal fluid (CSF) leak occurs in 1-11% of endoscopic Draf III, or endoscopic modified Lothrop, procedures. CSF leak can occur during surgery during a superior nasal septectomy. This study investigated whether the posterior edge of the nasofrontal beak (NFB) at the level of the internal frontal ostium is a safe landmark to use to avoid skull base injury when beginning the superior septectomy. Methods Preoperative computed tomography maxillofacial scans were reviewed from 100 patients from the University of Pennsylvania sinus surgery data base. The narrowest anteroposterior distance between the posterior edge of the NFB and the anterior aspect of the olfactory fossa (OF) at the level of the internal frontal ostium was measured in each patient. Measurements were taken in the midline and to the left and right of midline. Six fresh cadaver heads were also dissected to evaluate these relationships. Results On computed tomography analysis, the NFB was anterior to the OF on the left and right of the midline in 100% of the patients, with mean distances of 6.04 and 6.41 mm, respectively. The NFB was anterior to the OF in the midline in 98% of patients, with a mean distance of 9.02 mm. In all six cadavers, the posterior edge of the NFB was anterior to the OF in the midline and to the left and right of midline at the level of the internal frontal ostia. Conclusions During Draf III, the posterior edge of the NFB was a reliable landmark for avoiding iatrogenic CSF leak during the superior septectomy.

Outcomes after complete endoscopic sinus surgery and aspirin desensitization in aspirin-exacerbated respiratory disease: ESS and ASA desensitization for AERD

In this study we assessed patient outcomes after complete endoscopic sinus surgery (ESS) and aspirin desensitization for patients with aspirin‐exacerbated respiratory disease (AERD).

Temporal patterns of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography sinonasal uptake after treatment of sinonasal malignancy

Current guidelines have identified 10 to 12 weeks posttreatment as the ideal time‐point for improved diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) for deep tissue sites of the head and neck. After treatment, the sinonasal skull base is predisposed to prolonged inflammation that may render this time‐point inappropriate for initial posttreatment imaging surveillance for sinonasal malignancies. The purpose of this study is to evaluate temporal trends in 18F‐fluorodeoxyglucose (18FDG) sinonasal uptake after treatment for sinonasal malignancies to better elucidate the optimal time‐point for initial PET/CT posttreatment evaluation in this patient population.

Preoperative Lund-Mackay computed tomography score is associated with preoperative symptom severity and predicts quality-of-life outcome trajectories after sinus surgery: Lund-Mackay CT score and SNOT-22

Disagreement exists about the relationship between Lund‐Mackay CT scores (LMCTS) and quality‐of‐life outcome (QoL) measures. We investigated whether preoperative LMCTS are associated with preoperative QoL, and whether LMCTS is predictive of postoperative QoL outcomes in chronic rhinosinusitis (CRS) patients.

Quality-of-life Improvement after Endoscopic Sinus Surgery in Patients with Obstructive Sleep Apnea

Background There is preliminary evidence that patients with chronic rhinosinusitis (CRS) and comorbid obstructive sleep apnea (OSA) have reduced quality-of-life (QOL) improvements after functional endoscopic sinus surgery (FESS) compared with patients without OSA. The effect of OSA severity on QOL improvement after FESS is unknown. Objectives To better characterize the QOL improvement after FESS for patients with comorbid OSA and to assess whether QOL improvement is dependent on OSA severity. Methods This multi-institution, retrospective cohort study evaluated adult patients with CRS who underwent FESS between 2007 and 2015. Preoperative, 1-month, 3-month, 6-month, and 1-year postoperative 22-Item Sino-Nasal Outcome Test scores were used to evaluate QOL. We compared patients without OSA with patients with stratified OSA based on the preoperative apnea-hypopnea index. A multilevel, mixed-effects linear regression model was used for the analysis. Results Of 480 participants, 83 (17%) had OSA, and 47 of these patients had polysomnography results available for review. Both patients with OSA and patients without OSA reported significant QOL improvement after surgery (p < 0.0001) relative to baseline. In the unadjusted model, the subjects with OSA demonstrated a statistically worse outcome in 22-Item Sino-Nasal Outcome Test scores at each time point (2.4 points higher per time point, p = 0.006). When controlling for covariates, the adjusted model showed no difference in QOL outcome based on OSA status (p = 0.114). When stratified by OSA disease severity, the adjusted model showed no difference in the QOL outcome. Conclusions Patients with CRS and comorbid OSA had worse QOL outcomes after FESS; however, when controlling for patient factors, there was no difference in QOL outcome. OSA disease severity did not seem to predict QOL improvement after FESS.

Sinonasal quality of life after endoscopic resection of malignant sinonasal and skull base tumors

Improvement in sinonasal quality of life (QoL) following sinus surgery has been well‐documented across the literature. To our knowledge, only one series has evaluated long‐term QoL in patients undergoing tumor resection, and that study demonstrated no improvement in rhinologic QoL following malignant tumor resection at 2‐year follow‐up. The objective of the present study was to evaluate QoL in the 2 years following endoscopic malignant tumor resection.