The GSDMB rs7216389 SNP is associated with chronic rhinosinusitis in a multi-institutional cohort.

BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial disease with a high co-occurrence with asthma. In this multicohort study, we tested whether single nucleotide polymorphisms (SNPs) associated with childhood asthma and rhinovirus (RV)-associated disease are related to an increased susceptibility to adult CRS in a multicohort retrospective case-control study. METHODS: Participants at two tertiary academic rhinology centers, University of Arizona (UofA) and University of Pennsylvania (UPenn) were recruited. Cases were defined as those with physician diagnosed CRS (UofA, n = 149; UPenn, n = 250), and healthy controls were those without CRS (UofA, n = 66; UPenn, n = 275). Genomic DNA was screened for the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP. Gene dosage, or the number of combined risk alleles in a single subject was calculated. Meta-analysis of the association between GSDMB or CDHR3 genotypes and CRS was performed and additive gene dosage effect for each population calculated using p for trend. RESULTS: A meta-analysis revealed a combined increased risk for CRS in subjects with the GSDMB rs7216389 SNP (odds ratio [OR] 1.40; 95% confidence interval [CI], 1.16-1.76; p = 0.004). Both the UofA (OR 1.73; 95% CI, 1.23-2.43; p = 0.002) and UPenn (OR 1.27; 95% CI, 1.02-1.58; p = 0.035) populations showed a significant positive association between the number of combined risk alleles of GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP and risk for CRS. CONCLUSION: Carriers of the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP are at increased susceptibility for CRS. These data suggest that therapeutic approaches to target aberrant responses to RV infection may play a role in the treatment of unified airway disease.

The effect of maxillary sinus antrostomy size on the sinus microbiome.

BACKGROUND: The optimal maxillary antrostomy size to surgically treat sinusitis is not well known. In this study, we examined clinical metrics of disease severity and symptom scores, measured secreted inflammatory markers, and characterized the sinus microbiome to determine if there were significant differences in outcome between different maxillary ostial sizes. METHODS: Prospective randomized, single-blinded clinical trial enrolling 12 individuals diagnosed with recurrent acute or chronic rhinosinusitis. Each patient was blinded and randomized to receive minimal maxillary ostial dilation via balloon sinuplasty on 1 side vs a mega-antrostomy on the contralateral side. Data collected included symptom scores (20-item Sino-Nasal Outcome Test [SNOT-20]), endoscopy, and radiologic Lund-Mackay scores. During surgery and at their postoperative visit swabs were obtained from each maxillary sinus, and 16S DNA and inflammatory cytokine levels analyzed. The use of each patient as their own control allowed us to minimize confounding variables. RESULTS: There was statistically significant improvement in SNOT-20 symptom scores postoperatively in all patients. There were no significant differences between maxillary ostial size in postoperative endoscopy scores, cytokine profile, or bacterial burden. There were statistically significant differences in relative postoperative abundance of Staphylococcus, Lactococcus, and Cyanobacteria between the mega-antrostomy and mini-antrostomy. CONCLUSIONS: The method used in surgical maxillary antrostomies had no effect on endoscopy scores or cytokine profiles. Microbiome analysis determined significant differences between the different antrostomy sizes in postoperative Staphylococcus, Lactococcus, and Cyanobacteria abundance. The clinical significance of these changes in the sinus microbiome are not known but may be a result of increased access to postoperative sinonasal irrigations.

Diagnostic Pathway of Oral Cavity Cancer in an Integrated Health Care System.

CONTEXT: Survival for patients with oral cavity squamous cell carcinoma (OCSCC) has remained relatively stagnant despite advances in treatment. Few studies have examined why advanced-stage disease is diagnosed in 40% of patients with OCSCC nationally. OBJECTIVE: To characterize the diagnostic pathway of OCSCC in an integrated health care system. DESIGN: Retrospective study of patients with OCSCC (2007-2010). MAIN OUTCOME MEASURES: Referral patterns and demographic, clinical, and tumor characteristics associated with time to diagnosis (diagnostic interval). RESULTS: Of 247 patients, 167 (68%) had early-stage (I/II) disease, 86 (35%) were referred by dentists, and 70 (28%) had a history of premalignancy. The median time (interquartile range) from symptom onset to care sought from a primary care physician (patient interval), from primary care physician to otolaryngologist, and from otolaryngologist to diagnosis was 8.6 (4.0-25.8), 1.0 (0.6-3.1), 0.0 (0.0-3.0) weeks, respectively. These intervals did not differ by demographic characteristics, clinical factors, or tumor stage. Prolonged diagnostic intervals were observed among patients with premalignant lesions. CONCLUSION: The patient interval was the largest component of the total diagnostic interval. The subsequent professional workup proceeded relatively efficiently. Prolonged diagnostic interval in patients with premalignant lesions may reflect the natural history of malignant transformation rather than a delay in diagnosis. However, nearly one-fourth of these cases were diagnosed at an advanced stage; closer surveillance may represent an opportunity for diagnosis at an earlier stage. Surveillance for premalignant lesions and facilitating referrals from dentists may expedite the diagnosis and treatment of OCSCC. Further investigation is warranted.

Voice Outcomes of Adults Diagnosed with Pediatric Vocal Fold Nodules and Impact of Speech Therapy.

Objective To evaluate the voice outcomes of adults diagnosed with vocal fold nodules (VFNs) as children and to assess the impact of speech therapy on long-term voice outcomes. Study Design Prospective cohort study. Setting Large health care system. Subjects and Methods Subjects diagnosed with VFNs as children between the years 1996 and 2008 were identified within a medical record database of a large health care system. Included subjects were 3 to 12 years old at the time of diagnosis, had a documented laryngeal examination within 90 days of diagnosis, and were ≥18 years as of December 31, 2014. Qualified subjects were contacted by telephone and administered the Vocal Handicap Index-10 (VHI-10) and a 15-item questionnaire inquiring for confounding factors. Results A total of 155 subjects were included, with a mean age of 21.4 years (range, 18-29). The male:female ratio was 2.3:1. Mean VHI-10 score for the entire cohort was 5.4. Mean VHI-10 scores did not differ between those who received speech therapy (6.1) and those who did not (4.5; P = .08). Both groups were similar with respect to confounding risk factors that can contribute to dysphonia, although the no-therapy group had a disproportionately higher number of subjects who consumed >10 alcoholic drinks per week ( P = .01). Conclusion The majority of adults with VFNs as children will achieve a close-to-normal voice quality when they reach adulthood. In our cohort, speech therapy did not appear to have an impact on the long-term voice outcomes.

A rare and emerging entity: Sinonasal IgG4-related sclerosing disease.

BACKGROUND: Immunoglobulin G4 (IgG4) related sclerosing disease (rSD) is a new disease entity, first described in 2001, that involves autoimmune pancreatitis. Considered a systemic disease with lesions described in multiple organ systems, IgG4-rSD that affects the sinonasal region is rare. Our goal was to highlight the sinonasal presentation of this unique disease and to review previously reported adult cases from 2003 to 2014. METHODS: Case report (a 72-year-old man who presented with left exophthalmos, periorbital pain, and epiphora) and review of the literature. RESULTS: Radiographic workup with computed tomography and magnetic resonance imaging demonstrated a left sinonasal mass that involved the left maxillary and ethmoid sinuses, with surrounding bony destruction and orbital invasion. Nasal endoscopy demonstrated a fibrous lesion emanating in the middle meatus, with surrounding mucosal inflammation. The patient underwent an endoscopic biopsy, medial maxillectomy, and ethmoidectomy with tumor debulking. Pathology demonstrated inflamed respiratory mucosa with dense lymphoplasmacytic infiltrate and fibrosis; flow cytometry demonstrated no malignant cell populations; immunophenotyping demonstrated multiple foci of IgG4 cells. Plasma IgG4 was elevated in the setting of normal total IgG. The patient was treated with postoperative systemic and topical corticosteroids. Surveillance imaging studies and nasal endoscopy demonstrated disease resolution without recurrence. CONCLUSIONS: Sinonasal IgG4-rSD is a rare disease that can present with bony and soft-tissue invasion. This was an exceptional case, with osseous involvement and orbital invasion. Immunohistologic workup is essential for diagnosis. It is important to differentiate this disease from sinonasal tumors. Treatment includes corticosteroids and surgical debulking. Sinonasal IgG4-rSD represents an emerging disease that may present challenges for future rhinologists.