International Forum of Allergy & Rhinology

Kennedy, David W.

doi: 10.1002/alr.21624pmid: 26238101

Costa, Milena L.; Psaltis, Alkis J.; Nayak, Jayakar V.; Hwang, Peter H.

doi: 10.1002/alr.21533pmid: 25950995

Background Treatment indications for recurrent acute rhinosinusitis (RARS) remain poorly defined. We studied outcomes of medical vs surgical treatment of RARS, anatomic variants associated with RARS, and factors predicting crossover from medical to surgical treatment. Methods A total of 220 RARS patients treated between 2006 and 2014 were retrospectively divided into 3 cohorts: medical only (MED); surgical only (SURG); or medical crossing over into surgical (CROSS). Twenty‐two item Sino‐Nasal Outcome Test (SNOT‐22) scores, modified Lund‐Kennedy endoscopy scores, and prevalence of anatomic variants by computed tomography (CT) were compared. A total of 220 CT scans obtained for non‐sinus indications served as controls. A logistic regression model was used for analysis. Results The mean baseline SNOT‐22 scores for all cohorts were similar (MED = 48, SURG = 49, CROSS = 45, p < 0.0001). The SURG cohort showed greater reduction of SNOT‐22 scores compared to the MED cohort at 3, 6, and 12 months follow‐up (p < 0.0001). The crossover cohort converted to surgery after escalation of SNOT‐22 score by a mean of 15 points (p < 0.03), and showed significant reduction postoperatively (p < 0.0001). Haller cell (odds ratio (OR) 3.9; p < 0.0001), concha bullosa (OR 3.7; p < 0.003), and accessory ostium (OR 2.2; p < 0.01) were more common in the entire RARS group vs controls; however, there were no inter‐cohort differences in prevalence. Conclusion RARS patients can benefit from both medical and surgical treatment strategies, but surgical treatment results in greater symptomatic improvement compared to medical treatment. Patients cross over from medical to surgical treatment when SNOT‐22 scores escalate by a mean of 15 points. Haller cell, concha bullosa, and accessory ostium are associated with RARS but are equally common in medical, surgical, and crossover cohorts.

Tomoum, Mohamed O.; Klattcromwell, Cristine; DelSignore, Anthony; Ebert, Charles; Senior, Brent A.

doi: 10.1002/alr.21528pmid: 25952937

Background Both depression and anxiety have been suspected to impact quality of life adversely in patients with chronic rhinosinusitis (CRS). The objective of this work was to assess for the presence of anxiety and/or depression in the setting of CRS and to assess their impact on disease‐related quality of life by analyzing the correlation between the Rhinosinusitis Disability Index (RSDI) and the Hospital Anxiety and Depression score (HADS), as well as the Lund‐Kennedy nasal endoscopic scores. Methods A total of 124 patients with CRS were prospectively evaluated in the outpatient setting using the RSDI and HADS questionnaires as well as the Lund‐Kennedy nasal endoscopy scoring system. Results The total RSDI and its subscale scores had moderate to very strong correlation with the HADS total score and each of its subscale scores in comparison to their poor correlation with Lund‐Kennedy endoscopic score. CRS patients with depression or anxiety scores 8 to 10 (possible case of clinically significant depression or anxiety) and 11 to 21 (probable case) reported worse total RSDI and subscale scores when compared with those with normal scores (0 to 7). There was no significant difference in the Lund‐Kennedy endoscopic scores between the different groups of anxiety and depression scores. Conclusion Depression and anxiety are prevalent in CRS. The total RSDI and its different subscale scores exhibit moderate to very strong correlation with depression/anxiety scores as determined by HADS, whereas poor correlation was seen with the Lund‐Kennedy endoscopic score.

DeConde, Adam S.; Mace, Jess C.; Ashby, Shaelene; Smith, Timothy L.; Orlandi, Richard R.; Alt, Jeremiah A.

doi: 10.1002/alr.21539pmid: 26074476

Background Prior investigations into facial pain associated with chronic rhinosinusitis (CRS) have yielded important results, but have yet to use pain‐specific outcome measures. This study seeks to characterize facial pain associated with CRS using validated pain‐specific instruments. Methods Adults with CRS were enrolled into a prospective, cross‐sectional study along with control participants presenting with non‐CRS diagnoses. Facial pain was characterized in both groups using the Brief Pain Inventory Short Form (BPI‐SF) and the Short‐Form McGill Pain Questionnaire (SF‐MPQ). CRS‐specific measures of disease were measured including the 22‐item Sino‐Nasal Outcome Test‐22 (SNOT‐22), nasal endoscopy, and computed tomography scoring. Results The patients comprised of CRS with nasal polyposis (CRSwNP; n = 25), CRS without nasal polyposis (CRSsNP; n = 30), and control participants (n = 8). Subjects with CRSwNP and CRSsNP were less likely to be pain free than controls (16.0%, 6.7%, and 62.5% respectively, p = 0.001) and carried greater burden of pain as measured by the BPI‐SF and SF‐MPQ than controls (p = 0.002 and p = 0.017, respectively). Pain in CRS was most commonly located around the eyes and characterized as “throbbing” and “aching.” Nasal polyp status was not associated with differences in character, severity, or location of pain. Conclusion Subjects with CRS have a greater burden of facial pain relative to control subjects across several standardized pain measures. Further, facial pain in CRS significantly correlated to quality of life and CRS‐specific disease severity measures. Study across larger cohorts using standardized pain measures is warranted to clarify the association of facial pain with CRS.

DeConde, Adam S.; Suh, Jeffrey D.; Mace, Jess C.; Alt, Jeremiah A.; Smith, Timothy L.

doi: 10.1002/alr.21541pmid: 25907972

Background Functional endoscopic sinus surgery (FESS) was historically predicated on targeted widening of narrow anatomic structures that caused postobstructive persistent sinus inflammation. It is now clear that chronic rhinosinusitis (CRS) is a multifactorial disease with subsets of patients which may require a more extensive surgical approach. This study compares quality‐of‐life (QOL) and disease severity outcomes after FESS based on the extent of surgical intervention. Methods Participants with CRS were prospectively enrolled into an ongoing, multi‐institutional, observational, cohort study. Surgical extent was determined by physician discretion. Participants undergoing bilateral frontal sinusotomy, ethmoidectomy, maxillary antrostomy, and sphenoidotomy were considered to have undergone “complete” surgery, whereas all other participants were categorized as receiving “targeted” surgery. Improvement was evaluated between surgical subgroups with at least 6‐month follow‐up using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and the Brief Smell Inventory Test (B‐SIT). Results A total of 311 participants met inclusion criteria with 147 subjects undergoing complete surgery and 164 targeted surgery. A higher prevalence of asthma, acetylsalicylic acid (ASA) sensitivity, nasal polyposis, and a history of prior sinus surgery (p ≤ 0.002) was present in participants undergoing complete surgery. Mean improvement in SNOT‐22 (28.1 ± 21.9 vs 21.9 ± 20.6; p = 0.011) and B‐SIT (0.8 ± 3.1 vs 0.2 ± 2.4; p = 0.005) was greater in subjects undergoing complete surgery. Regression models demonstrated a 5.9 ± 2.5 greater relative mean improvement on SNOT‐22 total scores with complete surgery over targeted approaches (p = 0.016). Conclusion Complete surgery was an independent predictor of greater postoperative SNOT‐22 score improvement, yet did not achieve clinical significance. Further study is needed to determine the optimal surgical extent.

Scheel, Adam; Lin, Giant C.; McHugh, Jonathan B.; Komarck, Christine M.; Walline, Heather M.; Prince, Mark E.; Zacharek, Mark A.; Carey, Thomas E.

doi: 10.1002/alr.21524pmid: 26077310

Background The role of human papillomavirus (HPV) in sinonasal inverted papillomas (IPs) is controversial. Determining the prevalence of HPV infection and its impact on the molecular biology of these tumors is critical to characterizing its role in the pathogenesis of IPs. Methods A total of 112 paraffin‐embedded IPs from 90 patients were studied. A tissue microarray was constructed and stained for p16, p53, epidermal growth factor receptor (EGFR), and cyclin D1. HPV presence and types were determined using PGMY 09/11 primers and integration using HPV 11 detection of integrated papillomavirus sequences by ligation‐mediated polymerase chain reaction (DIPS‐PCR). Results HPV was detected in 11 of 90 (12%) patients. HPV 11 was found in 9 samples. HPV 6 and HPV 27 were found in 1 sample each. EGFR staining proportion was higher in HPV‐positive IPs vs HPV‐negative specimens (56.2% vs 23.6%; p = 0.009). Differences in p16, p53, and cyclin D1 staining were not significant. HPV‐positive lesions tend to progress to malignancy (p = 0.064). Three samples were analyzed for integration. Viral integration was found in both malignant tumors but not in the precursor IP. Conclusion Degradation of p53 and p16/cyclin D1 dysregulation are not important mechanisms in low‐risk HPV‐related IP. The low prevalence of HPV in this series indicates it is not a main etiological factor for IPs; however, when present, low‐risk HPV may contribute to the biology of IPs through an increase of EGFR expression and a predisposition for malignant progression by integration into the cellular genome.

Kim, Yong‐Dae; Bae, Chang Hoon; Song, Si‐Youn; Choi, Yoon Seok

doi: 10.1002/alr.21549pmid: 26010124

Background β‐Glucan is found in the cell walls of fungi, bacteria, and some plant tissues, and is detected by the innate immune system. Furthermore, this recognition is known to worsen respiratory symptoms in patients with allergic and inflammatory airway diseases. However, the means by which β‐glucan affects the secretion of major mucins by human airway epithelial cells has not been elucidated. Therefore, in this study, the effect and signaling pathway of β‐glucan on mucins MUC4 and MUC5B were investigated in human airway epithelial cells. Methods In NCI‐H292 cells and human normal nasal epithelial cells, the effect and signaling pathway of β‐glucan on MUC4 and MUC5B expression were investigated using reverse transcriptase–polymerase chain reaction (RT‐PCR), real‐time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA (siRNA). Results β‐Glucan increased MUC4 and MUC5B expression and activated the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB). SB203580 (a p38 MAPK inhibitor) and pyrrolidine dithiocarbamate (PDTC; a NF‐κB inhibitor) inhibited β‐glucan–induced MUC4 and MUC5B expression. In addition, siRNA knockdown of p38 MAPK blocked β‐glucan–induced MUC4 and MUC5B mRNA expression and β‐glucan–activated phosphorylation of NF‐κB. Furthermore, Toll‐like receptor 4 (TLR4) mRNA expression was increased by β‐glucan, and siRNA knockdown of TLR4 blocked β‐glucan–induced MUC4 and MUC5B mRNA expression and β‐glucan–activated phosphorylation of p38 MAPK and NF‐κB. Conclusion These results demonstrate that in human airway epithelial cells β‐glucan induces MUC4 and MUC5B expression via the TLR4–p38 MAPK–NF‐κB signaling pathway.

Sigsgaard, Torben; Thorne, Peter S.; Schlünssen, Vivi; Bønløkke, Jakob; Riddervold, Ingunn S.; Hoppe, Kimberly A.; Andersen, Niels Trolle; Mackenzie, Neill M.

doi: 10.1002/alr.21534pmid: 25851155

Zhang, Zi; Adappa, Nithin D.; Doghramji, Laurel J.; Chiu, Alexander G.; Cohen, Noam A.; Palmer, James N.

doi: 10.1002/alr.21532pmid: 25899601

Background Staphylococcus aureus and Pseudomonas aeruginosa are common culture isolates in chronic rhinosinusitis (CRS). We aimed to determine whether they were associated with different clinical factors of CRS. Methods Adult CRS patients who underwent functional endoscopic sinus surgery (FESS) between October 1, 2007 and December 31, 2011 were recruited. Patient demographics, Lund‐Mackay computed tomography (CT) scores, 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores, disease characteristics, and medication use were collected prior to FESS. Intraoperative culture was obtained in a standard manner. We compared patients with isolates of S. aureus or P. aeruginosa to patients with other culture results and no bacterial growth, respectively. Multivariate logistic regression was performed. Results A total of 376 patients met criteria; 104 patients (28%) had S. aureus, 32 (9%) had P. aeruginosa, and 10 patients (3%) had no bacterial growth. After adjusting for all clinical factors, compared to patients with positive culture other than S. aureus, patients with S. aureus had 1.9 times increased odds of having nasal polyps (odds ratio (OR) = 1.9; 95% confidence interval (CI), 1.0 to 3.3; p = 0.036); when compared to patients with positive culture other than P. aeruginosa, patients with P. aeruginosa had 7.8 times increased odds of having prior FESS (OR = 7.8; 95% CI, 2.1 to 28.9; p = 0.002) (91% vs 58%; p < 0.001) and 3.6 times increased odds of having diabetes with marginal significance (OR = 3.6; 95% CI, 1.0 to 13.2; p = 0.053). The sample size in the no bacterial growth group was too small to draw firm conclusions. Conclusion S. aureus was more common in CRS patients with nasal polyps, whereas P. aeruginosa was more common in CRS patients with prior FESS history and possibly diabetes.

Yu, Zhijian; Wang, Yu; Zhang, Jia; Li, Lei; Wu, Xingmei; Ma, Renqiang; Han, Miaomiao; Xu, Geng; Wen, Weiping; Li, Huabin

doi: 10.1002/alr.21530pmid: 25907676

Background Oxidative stress is characteristic of chronic airway inflammatory diseases such as asthma, chronic obstructive pulmonary disease and chronic rhinosinusitis with nasal polyps (CRSwNP). Heme oxygenase (HO)‐1 has been proposed to be a cytoprotective enzyme against oxidative stress in CRSwNP. However, the expression and regulation of HO‐1 in eosinophilic CRSwNP (ECRS) and non‐eosinophilic CRSwNP (non‐ECRS) subsets has not been well documented. Methods Nasal polyps and uncinate process tissues were enrolled from 40 CRSwNP patients (ECRS, 17; non‐ECRS, 23) and 20 control subjects, respectively. The messenger RNA (mRNA) and protein expression of HO‐1 was examined using qRT‐PCR, immunohistochemistry, and Western blot staining. Moreover, the stimulatory effects of several cytokines (interferon γ (IFN‐γ), interleukin (IL)‐5, and IL‐13, etc.) on HO‐1 mRNA expression in cultured nasal explants were evaluated. Results The mRNA and protein expression of HO‐1 was significantly increased in polyp tissues compared with healthy controls (p < 0.05), and the non‐ECRS subset showed significantly increased HO‐1 expression compared with the ECRS subset (p < 0.05). Moreover, in cultured nasal explant, HO‐1 mRNA was significantly upregulated in the presence of IFN‐γ, IL‐27, IL‐5, IL‐13, and IL‐17A, but was significantly inhibited by transforming growth factor β1 (TGF‐β1) (p < 0.05). Conclusion Our findings indicate that HO‐1 was differentially expressed and regulated in ECRS and non‐ECRS patients.