NA. Laryngoscope, 128:E304-E310, 2018.

Background Complement plays a major role in inflammatory diseases but its involvement and mechanisms of activation in chronic rhinosinusitis (CRS) are not known. Objectives Following earlier studies discovering autoantibodies in CRS, we sought to investigate the nature, extent, and location of complement activation in nasal tissue of patients with CRS. Specifically, we were interested in whether antibody-mediated activation via the classical pathway was a major mechanism for complement activation in CRS. Methods Nasal tissue was obtained from patients with CRS and control patients. Tissue homogenates were analyzed for complement activation products (ELISA-C5b-9, C4d, activated C1 and C5a) and major complement fixing antibodies (Luminex). Tissue sections were stained for C5b-9, C4d, and laminin. Antibodies were purified using protein A/G columns from nasal polyps (NP), matching patient serum and control serum, and assayed for basement membrane binding via ELISA. Results C5b-9 was significantly increased in NP tissue compared to UT (uncinate tissue) of CRS with NP (CRSwNP) and CRS without NP (CRSsNP) (p<0.01). Similarly, C4d was increased in NP compared to UT of CRSwNP, CRSsNP and control (p<0.05). Activated C1 was also increased in NP tissue compared to UT of CRSsNP and control (p<0.05) and was correlated with C5a (p<0.01), local immunoglobulins, especially IgM (p<0.0001) and anti-dsDNA IgG (p<0.05). Immunofluorescence showed that C5b-9 and C4d deposition occurred linearly along the epithelial basement membrane. NP tissue extracts had significantly more anti-basement membrane antibodies than sera from CRSwNP and control patients (p<0.0001). Conclusion C5b-9, C4d and activated C1 were significantly increased locally in NP tissue. C5b-9 and C4d were almost universally deposited linearly along the basement membrane of NP tissue. Furthermore, activated C1 was best correlated with local immunoglobulin levels and C5a levels. Together, these data suggest that the classical pathway plays a major role in complement activation in CRS.

No abstract

In normal volunteers, surfactant nasal irrigation may be associated with tolerability issues due to congestion. A subset may experience reduction in olfactory acuity that appears reversible.

Background Inflammatory patterns in chronic rhinosinusitis (CRS) may predict disease severity, need for multiple sinus surgeries, and treatment response. This study analyzes nasal mucus inflammatory cytokine patterns in patients with (CRSwNP) and without (CRSsNP) nasal polyposis and their association with revision sinus surgery. Methods A total of 319 CRS patients who underwent sinus surgery were included. Cytokines were quantified in intraoperative mucus specimens using a multiplex flow cytometric bead assay. Cytokine expression patterns in patients with 0, 1, and ≥2 previous surgeries were analyzed using Kruskal‐Wallis and principal component (PC) regression analyses. Results There were 122 (38%) patients with CRSsNP and 197 (62%) with CRSwNP. On univariate analysis, interleukin (IL)‐1β, IL‐6, IL‐8, and IL‐21 were associated with increasing number of sinus surgeries in CRSsNP, as were IL‐2, IL‐4, IL‐5, IL‐6, IL‐9, IL‐17A, and tumor necrosis factor (TNF)‐α in CRSwNP. PC analysis with continuous Poisson regression in CRSwNP demonstrated that high IL‐5 and IL‐13 and low IL‐1β, IL‐12, and IL‐21 were associated with more prior surgeries. In CRSsNP low IL‐13 and high IL‐5 and regulated‐on‐activation, normal T‐cell–expressed and secreted (RANTES) were associated with more prior surgeries. Age remained a significant covariate in the full regression model for CRSsNP, but was nonsignificant in CRSwNP. Conclusion In CRSwNP, elevated IL‐5 and IL‐13 levels were higher at time of surgery in patients with more prior surgeries. Type 2 cytokines in CRSsNP demonstrated mixed associations with revision surgery. For both phenotypes, IL‐10, IL‐12, and IL‐21 were consistently lower as number of prior surgeries increased, suggesting that treatment‐resistant disease may be modulated by impairment in these signaling pathways.

No abstract

Objectives Recent increases in opioid‐related mortality have prompted a critical evaluation of postoperative pain management across all specialties. However, successfully limiting narcotic overprescription requires perioperative identification of patients who are at risk for high postoperative pain. Unfortunately, quality data to guide practice patterns are lacking. We therefore prospectively investigated several possible predictive factors of postoperative pain after endoscopic sinus surgery (ESS). Methods Sixty‐four consecutive patients undergoing ESS were enrolled. Baseline 22‐item SinoNasal Outcomes Test (SNOT‐22) and Short‐Form 8 (SF‐8) scores were obtained. Pain scores were collected postoperatively using a numeric rating scale. Spearman correlations and univariate linear regression models were used to investigate relationships between postoperative pain, patient factors, and SNOT‐22/SF‐8 domain scores. Multivariate linear regression was then performed to control for potential confounding variables. Results Day‐of‐surgery pain scores were significantly correlated with the SF‐8 role‐physical domain (Rs = 0.32, P = 0.04). Whereas SF‐8 pain scores were initially nonsignificant, at postoperative day 3 (POD3) the preoperative SF‐8 pain score became correlated with self‐reported pain (Rs = 0.39, P = 0.02). SNOT‐22 total and subdomain scores were not associated with pain scores at any time point. Multivariate linear regression modelling identified baseline SF‐8 role‐physical and pain scores, smoking status, and undergoing a modified Lothrop procedure as significant independent predictors of POD3 pain (adjusted R2 = 0.359, P < 0.0001). Conclusion Baseline patient‐reported global quality‐of‐life measures are associated with postoperative pain after ESS. Large multicenter studies are necessary to validate these findings and investigate additional factors associated with postoperative pain following ESS. Level of Evidence 2c Laryngoscope, 129:1274–1279, 2019

Background Polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells and fibrin deposition. Anti‐phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS). Objective To compare APA levels (anti‐cardiolipin, anti‐phosphatidylethanolamine (anti‐PE), and anti‐β2‐glycoprotein (anti‐B2GP)) in nasal polyp (NP) tissue with tissue from control and CRS without nasal polyp (CRSsNP) patients, we tested whether NP antibodies affect coagulation, and correlate APAs with anti‐dsDNA IgG and markers of coagulation. Methods Patient specimens were assayed for APA IgG, anti‐dsDNA IgG and thrombin‐anti‐thrombin (TaT) complex by ELISA. Antibodies from a subset of specimens were tested for modified activated partial thromboplastin time (aPTT) measured on an optical‐mechanical coagulometer. Results Anti‐cardiolipin IgG in NP was 5‐fold higher than control tissue (p < .0001). NP antibodies prolonged aPTT compared to control tissue antibodies at 400 µg/mL (36.7 s vs. 33.8 s, p = .024) and 600 µg/mL (40.9 s vs. 34.7 s, p = .0037). Anti‐PE IgG antibodies were increased in NP (p = .027), but anti‐B2GP IgG was not significantly higher (p = .084). All APAs correlated with anti‐dsDNA IgG levels, which were also elevated (R = .77, .71 and .54, respectively, for anti‐cardiolipin, anti‐PE, and anti‐B2GP; all p < .001), but only anti‐cardiolipin (R = .50, p = .0185) and anti‐PE (R = 0.45, p = .037) correlated with TaT complex levels. Conclusions APA IgG antibodies are increased in NP and correlate with autoreactive tissue antibodies. NP antibodies have in vitro anti‐coagulant activity similar to those observed in anti‐phospholipid syndrome, suggesting that they may have pro‐coagulant effects in polyp tissue.