The impact of chronic rhinosinusitis on long-term survival in lung transplantation recipients

CONCLUSIONS: Chronic rhinosinusitis diagnosed according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2012, not by computed tomography alone, is one of the prognostic factors affecting long-term survival in patients with lung transplantation. Endoscopic sinus surgery might play a beneficial role in the management of lung transplantation recipients with chronic rhinosinusitis. OBJECTIVE: To show the effect of paranasal sinus infection on post-lung transplantation survival. METHOD: Lung transplantation recipients were included in this study. Computed tomography was performed before and after lung transplantation. The severity of chronic rhinosinusitis was evaluated by Lund-Mackay scoring system. The survival rate was calculated by the Kaplan-Meier method. RESULTS: One hundred and forty-eight patients received lung transplantation for various indications. Chronic rhinosinusitis was found in 18.9% (28/148) of the lung transplantation recipients. Of 28 patients with chronic rhinosinusitis, seven patients underwent endoscopic sinus surgery due to persistent post-nasal drip. The recipients with chronic rhinosinusitis who did not receive endoscopic sinus surgery (n = 21) showed a significantly lower survival rate as compared to the patients without chronic rhinosinusitis. There was no statistically significant difference in the survival rate between the recipients with (n = 50) and without (n = 98) paranasal sinus abnormality on computed tomography

Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis

Background: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). Methods: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course. Results: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field. Conclusions: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence

Determining an Appropriate Time to Start Prophylactic Treatment with Intranasal Corticosteroids in Japanese Cedar Pollinosis

: Prophylactic treatment with intranasal corticosteroids is effective for pollen-induced seasonal allergic rhinitis. However, the appropriate time to start this treatment remains unclear. We performed a double-blinded, randomized, placebo-controlled trial. Starting on February 1, 2014, patients with Japanese cedar pollinosis received either fluticasone furoate nasal spray (FFNS) for 8 weeks (Group A: n = 24), placebo nasal spray for 2 weeks followed by FFNS for 6 weeks (Group B: n = 23), or placebo for 4 weeks followed by FFNS for 4 weeks (Group C: n = 23). The primary endpoint was comparison of the total naso-ocular symptom score (TSS). Secondary endpoints including the increment cost effective ratio (ICER) were also determined. Continuous pollen dispersion began on the 24th of February. Therefore, Group A and Group B received 3-weeks and 1-week of prophylactic treatment, respectively, whereas Group C received post-onset treatment. During the peak pollen-dispersal period, significant differences in TSS were seen between the groups, particularly between Group A and C. The ICER of Group B vs. Group C was lower than that of Group A vs. Group C. These results suggest that long-term prophylactic treatment with FFNS is clinically the most potent treatment, whereas short-term prophylactic treatment is cost effective for pollen-induced allergic rhinitis

Effect of intranasal corticosteroid on pre-onset activation of eosinophils and mast cells in experimental Japanese cedar pollinosis

Background: Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated. Methods: We designed a double-blinded, randomized, placebo-controlled, crossover trial. Twenty patients with JCP were examined outside the pollen season (UMIN000008410). Nasal provocation with paper discs containing extracts of Japanese cedar pollen was performed once a day for 3 consecutive days. Onset of nasal symptoms was monitored over 15 min after each provocation. The levels of eosinophil cationic protein (ECP) and tryptase in nasal secretions were examined. Fluticasone furoate nasal spray or placebo treatment was started one day before the first provocation. Results: In the placebo group, 25% of the patients showed onset of nasal symptoms following provocation on the first day. In addition, 75% and 68% of the patients showed symptom onset on the second and third day of provocation, respectively. After the first provocation, the levels of ECP and tryptase in nasal secretions were significantly increased. These increases were seen not only in symptomatic but also in asymptomatic subjects in response to provocation, and the levels were similar between these subjects. Prophylactic treatment with fluticasone significantly suppressed the increase in nasal ECP and tryptase associated with repeated provocations. Conclusions: These results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation

Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts

Background: Vascular endothelial growth factor (VEGF) is known to be associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). VEGF is produced by a variety of cells including fibroblasts. It was recently reported that prostaglandin (PG) E2 induces VEGF release by nasal polyp fibroblasts. However, little is known regarding possible regulation of VEGF by other PGs. We have reported that molecules that regulate PGD2 metabolism play roles in the pathogenesis of CRS including in local eosinophilia and type 2 cytokine production. In the present study, we sought to determine whether PGD2 regulates VEGF release by nasal polyp fibroblasts. Methods: Nasal polyp fibroblasts were established from nasal polyps. These fibroblasts were stimulated with serial dilutions of PGD2 or PGD2 receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. The concentration of VEGF in the culture supernatants was determined using ELISA. Results: 5 μM of PGD2 significantly induced VEGF release by nasal polyp fibroblasts. VEGF release was also obtained by stimulation with a DP receptor-selective, but not with a CRTH2 receptor-selective agonist. In addition, PGD2-induced VEGF release was significantly inhibited by pre-treatment with DP receptor-selective antagonists. In contrast, pre-treatment with a CRTH2 receptor-selective antagonist significantly enhanced PGD2-induced VEGF release. Conclusions: PGD2 stimulates VEGF production via DP but not CRTH2 receptors in nasal polyp fibroblasts