CRSsNP Group Research Articles

Endotyping of Chronic Rhinosinusitis With and Without Polyp Using Transcription Factor Analysis.

Inflammation of the nose and paranasal sinus or rhinosinusitis (RS) is a significant global health problem that is both very common and very costly to treat. Previous reports reveal variability in histology and mechanism of inflammation in patients with chronic rhinosinusitis with and without polyp (CRScNP and CRSsNP, respectively). There are various methods and hypothesis that try to explain this variability. Accordingly, the aim of this study was to investigate the incidence of each type of sinonasal inflammation among patients diagnosed with CRScNP or CRSsNP using transcription factor analysis (TFA). This study included mucosa specimens from nose/paranasal sinuses from patients with chronic rhinitis (CR), CRSsNP, or CRScNP that were obtained at the Department of Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during the June 2009 to May 2012 study period. TFA was employed to measure the following transcription factors: T-box transcription factor (T-bet) for Th1, GATA binding protein 3 (GATA-3) for Th2, retinoic acid-related orphan receptor C (RORC) for Th17, and forkhead box P3 (FOXP3) for Treg. Forty-one subjects (22 males, 19 females) were enrolled, with a mean age of 45.93 ± 13 years. Twenty-six patients were diagnosed with CRScNP, 7 with CRSsNP, and 8 with CR (controls). The majority of CRScNP specimens (76.9%) had eosinophil count greater than 100 cells/high-power field (HPF). Mean eosinophil count was 930.08 ± 1,399 cells/HPF (range: 17–5,570). Th2 transcription factor (GATA-3) was statistically significantly higher in the CRScNP group than in the CRS and control groups (p < 0.001); whereas, Treg transcription factor (FOXP3) was statistically significantly lower in the CRScNP group than in the CRSsNP and control groups (p < 0.001). The transcription factors for Th1 and Th17 (T-bet and RORC, respectively) were not significantly different among the three groups. The result of transcription factor analysis revealed hyperfunction of Th2 in patients with CRScNP, which might result in hypereosinophilic infliltration in the polyps. One explanation for this finding is the decreased activity of Treg. Although environment-host interaction is the most probable hypothesis, the etiology of aberrant adaptive immunity needs to be elucidated.

The kinase LRRK2 is differently expressed in chronic rhinosinusitis with and without nasal polyps

BackgroundChronic rhinosinusitis (CRS), commonly divided into CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is an inflammatory disease which mechanism remain unclear. Leucine-rich repeat kinase 2 (LRRK2) has been proved to be a negative regulator of inflammation response while its role in pathogenesis of CRS has yet to be revealed. This research study was designed to investigate the relationship between the expression level and biologic role of LRRK2 in CRS.MethodsExpression of LRRK2 mRNA and noncoding repressor of NFAT (NRON) were examined by qRT-PCR. Protein levels of LRRK2 were performed by western blot and immunohistochemistry. Nuclear factor of activated T cells (NFAT) nuclear translocation was analyzed by immunohistochemistry. Additionally, LRRK2 mRNA and NRON expression in response to specific inflammatory stimulation was measured in human nasal epithelia cells (HNECs).ResultsThe expression of LRRK2 was increased in CRSsNP patients (p < 0.05) and positively correlated with the expression levels of CD3 and Charot-Leyden crystal. Meanwhile, the NRON expression level is much lower in CRSsNP patients compared to both the control group and CRSwNP group (p < 0.05). Marked enhanced NFAT nuclear localization was observed in CRSwNP groups compared with the CRSsNP and control group (p < 0.0001). And the over-expression of LRRK2 was significantly regulated by lipopolysaccharide (LPS) in HNECs (p < 0.05). Moreover, IL-17A can increase LRRK2 expression and suppress NRON expression in vitro and dexamethasone can rescue the NRON inhibition.ConclusionLRRK2 and NRON may play different role in CRSsNP and CRSwNP. The molecular mechanisms identified here may aid in the design of novel therapeutic strategies to improve clinical outcomes.

Eustachian Tube dysfunction in chronic rhinosinusitis: pre and post-operative results following endoscopic sinus surgery, a prospective study.

Prospective study investigating the incidence of concurrent Eustachian Tube dysfunction (ETD) in patients with CRS refractory to medical therapy, and the effect of Endoscopic Sinus Surgery (ESS) on ETD in this patient group. Prospective study of 57 CRS patients. Outcome measures were SNOT-22 and ETDQ-7 questionnaires, tympanometry and Valsalva manoeuvre recorded pre-operatively and at 3 and 9 months post ESS. There was a moderate positive correlation between pre-operative ETDQ-7 and SNOT 22 scores (r equals 0.5715, p less than 0.0001). 68% of patients recorded positive ETDQ-7 scores pre-operatively, mean equals 20.6 (SD plus or minus 10.34). Mean ETDQ-7 scores were significantly lower at 3 months; mean equals 11.4 (SD plus or minus 5.65) (P less than 0.0001) and 9 months mean equals 11.4 (SD plus or minus 6.15) (P less than 0.0001) following ESS. Type A tympanograms increased form 76.6% pre-operatively, to 94.5% at 3 months and 96% at 9 months. Reported positive Valsalva increased from 38% pre-operatively to 96% at 3 and 9 months. Mean ETDQ-7 scores were higher in the CRSwNP group; 24.34 (SD plus or minus 9.2) compared to the CRSsNP group; 18.11 (SD plus or minus 10.3), (p equals 0.6101). 16 patients in the cohort had existing diagnoses of asthma, of which 4 had documented aspirin sensitivity. The mean pre-operative SNOT-22 score in this overall subgroup was 64.81 (SD equals plus or mins 20.13) compared with 49.07 (SD equals plus or minus 21.37) in non-asthmatic patients (p equals 0.0168). We found a high incidence of concurrent ETD symptoms in patients with severe CRS, which improve following ESS. Further research is required to better understand the association between CRS and ETD in order to provide effective treatments.

PepsinA as a Marker of Laryngopharyngeal Reflux Detected in Chronic Rhinosinusitis Patients.

Objectives We aimed to confirm the presence of pepsinA in the nasal secretions and tissues of chronic rhinosinusitis (CRS) patients and reveal the relationship between CRS and laryngopharyngeal reflux (LPR). Study Design Cross-sectional study. Setting The study was conducted at the Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University. Subjects and Methods A total of 32 CRS patients with or without nasal polyps (CRSwNP and CRSsNP, respectively) and 10 normal controls were enrolled in our study. We investigated the expression of pepsinA in the nasal tissues, secretions, and blood plasma from the subjects by immunohistochemical staining, Western blot, or ELISA. Additionally, the expressions of MUC4, MUC5AC, MUC5B, MUC8, and pepsinogenA in nasal tissue were evaluated by quantitative real-time polymerase chain reaction. Results Immunohistochemistry and Western blot revealed that the pepsinA expression levels in the turbinate mucosa in CRSwNP/CRSsNP patients, which were largely restricted to the epithelial layer or glandular mucous cells in nasal tissues, were significantly higher than those in controls and in the polyp tissues of CRSwNP patients ( P < .05). In addition, the concentration of pepsinA in nasal secretions was significantly increased in the CRSwNP (147.85 ± 53.69 ng/mL, P < .001) and CRSsNP (134.12 ± 36.23 ng/mL, P < .001) groups as compared with the controls (68.69 ± 19.28 ng/mL). Although MUC5AC, MUC5B, and MUC8 expression differed among the groups, no correlation between pepsinA and mucin genes was found. Conclusion The results of this study provided evidence of an association between LPR and CRS, although no correlation was found to exist between LPR and mucin genes in CRS patients.

The Lung Function Impairment in Non-Atopic Patients With Chronic Rhinosinusitis and Its Correlation Analysis.

Objectives Chronic rhinosinusitis (CRS) is common disease in otorhinolaryngology and will lead to lower airway abnormality. However, the only lung function in CRS patients and associated factors have not been much studied.Methods One hundred patients with CRS with nasal polyps (CRSwNP group), 40 patients with CRS without nasal polyps (CRSsNP group), and 100 patients without CRS were enrolled. The difference in lung function was compared. Meanwhile, CRSwNP and CRSsNP group were required to undergo a bronchial provocation or dilation test. Additionally, subjective and objective outcomes were measured by the visual analogue scale (VAS), 20-item Sino-Nasal Outcome Test (SNOT-20), Lund-Mackay score, Lund-Kennedy endoscopic score. The correlation and regression methods were used to analyze the relationship between their lung function and the above parameters.Results The forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) of CRSwNP group were significantly lower than other groups (P<0.05). On peak expiratory flow, there was no difference between three groups. In CRSwNP group, FEV1 was negatively correlated with peripheral blood eosinophil count (PBEC) and duration of disease (r=–0.348, P=0.013 and r=–0.344, P=0.014, respectively), FEF25-75 negatively with VAS, SNOT-20 (r=–0.490, P=0.028 and r=–0.478, P=0.033, respectively) in CRSsNP group. The incidence of positive bronchial provocation and dilation test was lower in CRSwNP group (10% and 0%, respectively), with both 0% in CRSsNP group. The multiple linear regression analysis indicated that change ratio of FEV1 before and after bronchial provocation or dilation test were correlated with PBEC in CRSwNP group (β=0.403, P=0.006).Conclusion CRS leading to impaired maximum ventilation and small airway is associated with the existence of nasal polyp. Lung function impairments can be reflected by PBEC, duration, VAS, and SNOT-20. In CRSwNP patients, PBEC is independent predictor of FEV1 change ratio.

Effect of paranasal anatomical variants on outcomes in patients with limited and diffuse chronic rhinosinusitis

ObjectiveThe role of anatomical variants of the paranasal sinuses in the aetiology of chronic rhinosinusitis (CRS) is not well understood. Furthermore, the effect of anatomical variants on long-term outcomes has not been described. This study aims to assess the effects of anatomical variants of the middle meatus on patients with limited and diffuse CRS. MethodsA database analysis was conducted for patients with limited sinusitis (undergoing anterior FESS) and patients with diffuse sinusitis (undergoing complete FESS) between 2009 and 2013. Intergroup comparisons were made for symptom scores, CT scans, revision surgery, re-referrals following discharge and number of clinic follow-ups. ResultsA total of 86 patients were included in the study: 40 anterior FESS, 25 CRSwNP and 21 CRSsNP. Following surgery, anterior FESS symptom scores reduced by 4.6±0.8 on average, while the CRSwNP and CRSsNP group reduced by 5.7±1.1 and 5.9±1.3 respectively. Patients undergoing anterior FESS required fewer clinic follow-ups than CRSwNP (Δ 2.7±0.9, P<0.001) and CRSsNP (Δ 3.3±0.6, P<0.001). Patients with fewer anatomical variants (0–2) required more follow-up (5.2±0.6) than those with higher numbers of variants (3+) (3.8±0.3, P=0.05). No significant differences were seen between groups for revision surgery, repeat CT and re-referral rates. ConclusionLimited surgery for local disease demonstrated comparable symptom improvement to patients with extensive disease receiving extensive surgery. Patients with greater numbers of anatomical variants are associated with localised sinus disease who typically require less postoperative care after receiving limited surgery.

The role of IL-25 and IL-33 in chronic rhinosinusitis with or without nasal polyps.

The role of IL-25 and IL-33 in the aetiology and pathogenesis of nasal polyps has been controversial in the literature. The objective of the study is to detect serum and tissue levels of IL-25 and IL-33 in patients with (CRSwNP) or without (CRSsNP) nasal polyps using enzyme-linked immunosorbent assay (ELISA). Study group consisted of 20 CRSwNP and 20 CRSsNP patients. Control group comprised of 20 volunteers who had been operated with septum deviation without any additional sinonasal pathology, allergy, systemic disease, or medication use. All groups preoperatively underwent paranasal CT examinations and sinonasal pathologies were recorded based on Lund-Mackay radiological staging system. IL-25 and IL-33 levels in serum and tissue samples were analyzed using the ELISA method. Serum IL-25 and IL-33 levels in CRSsNP, CRSwNP, and control groups did not differ statistically significantly (p=0.345 and p=0.338). Any statistically significant difference was not detected in mean tissue IL-25 levels among CRSsNP, CRSwNP, and control groups (p=0.698). Mean tissue IL-33 level in the CRSwNP group was statistically significantly lower when compared with those of CRSsNP and control groups (p<0.001 and p<0.001, respectively). A statistically significant negative correlation was detected between tissue IL-33 levels and Lund-Mackay CT scores (r=-0.436 and p=0.005). In the present study, we conceivably contributed to scarce number of studies conducted on this issue and we think that further studies will better clarify the role of IL-25 and IL-33 in the development of nasal polyps.

Bacteriology of the Middle Meatus in Chronic Rhinosinusitis with and without Polyposis

There are only limited data in the literature, and none specifically from the Middle East, on the pathogenic bacteria in chronic rhinosinusitis (CRS) as opposed to healthy nasal cavities and their association with disease severity. The present study was conducted in the department of head and neck surgery of a tertiary medical center. Middle meatal swabs were taken preoperatively from patients with CRS with nasal polyposis (CRSwNP) (n = 60), CRS without nasal polyposis (CRSsNP) (n = 50), and control patients with septal deviation (n = 26) or no nasal abnormalities (n = 27). Culture findings were compared among the groups and correlated with CRS severity. Positive pathogenic culture rates were 78% in the CRSwNP group and 64% in the CRSsNP group. Twenty pathogenic bacterial species were identified; the most common was Staphylococcus aureus (27%). The most common Gram-negative isolate was Citrobacter spp. (17%). Gram-negative species were significantly more prevalent in the CRSwNP group than the others. Mean Lund-Mackay scores were 12.8 in the CRSwNP group and 6.9 in the CRSsNP group, and were unrelated to the culture findings. Positive culture rates were significantly higher in the septal deviation (54%) than the nasal healthy group (26%), although both values were significantly lower than in the CRS groups. In conclusion, patients with CRS have higher rates of bacterial isolates than patients without CRS. CRSwNP is associated with more Gram-negative bacteria than CRSsNP, regardless of disease severity. The relatively high positive culture rate in patients with septal deviation merits investigation.

T regulatory and Th17 cells in chronic rhinosinusitis with polyps.

Chronic rhinosinusitis (CRS) is categorized into 2 types based on the absence (CRSsNP) and presence of nasal polyps (CRSwNP). Although CRSsNP patients lack nasal polyps, the mucosa may show variable degrees of polypoid change. This raises the question of whether or not the classification system is an over simplification and that CRSsNP and CRSwNP only represent 2 phenotypic extremes along a broader spectrum of immunologically different disease processes. To investigate this, adaptive and innate immune cells were compared in the different tissue types within CRSsNP and CRSwNP patients. Tissue from 15 CRSwNP, 6 CRSsNP, and 8 healthy control patients was obtained prospectively. Nonpolypoid mucosa, polypoid tissues, and polyps were obtained at the time of endoscopic sinus surgery and analyzed using flow cytometry for various adaptive and innate immune cell subsets. In the polyps from CRSwNP patients there were significantly more T regulatory (Treg) cells (12.86 ± 12.60 vs 2.83 ± 4.68) and Th17 cells (16.12 ± 11.75 vs 2.31 ± 2.13) compared to the polypoid tissue from CRSsNP patients. Cellular infiltrates in the nonpolypoid or polypoid mucosa of the different patient categories showed no difference in CRSwNP, CRSsNP and control groups. This observational study identified an increase in Treg and Th17 cells in CRSwNP patients implying that these cells may be implicated in polyp development. Importantly it also identified a similar inflammatory infiltrate in nonpolyp or polypoid mucosa across control, CRSsNP, and CRSwNP groups inferring that polyps should be sampled when studying CRSwNP.

Interleukin-9 and interleukin-17C in chronic rhinosinusitis.

Interleukin (IL)-9 and IL-17C have been known to play a role in allergic inflammation, yet, their roles in chronic rhinosinusitis (CRS) are not well defined. IL-9 induces changes in epithelial cell gene expression leading to goblet cell metaplasia, whereas IL-17C is functionally distinct in that its expression can be induced by bacterial challenge and inflammatory stimuli. This study aimed to compare levels of IL-9 and IL-17C in CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) as well as atopy. Nasal polyp or sinus mucosal specimens from CRSwNP (n = 36), CRSsNP (n = 9), and control (n = 9) groups were collected and processed. Patient atopy status was determined by history of skin-prick test and pulmonary function test. Immunohistochemistry was carried out using anti-human IL-9 and IL-17C antibodies. Positively-stained cells were enumerated under high-power (×400) magnification in 5 consecutive fields. The level of expression of IL-9 was higher in CRSwNP than CRSsNP and control. Similar findings were demonstrated in IL-17C with higher expression in CRSwNP than CRSsNP and control. Both the averages of positively-stained cells expressing IL-9 and IL-17C were higher in CRS with asthma and allergy compared to control. This suggested that IL-9 and IL-17C were both involved in the pathogenesis of CRS, allergy, and asthma. Inflammatory cell expression of IL-9 and IL-17C were increased in CRS, particularly with allergy and asthma. These interleukins may contribute to the pathogenesis of CRSwNP as well as atopy and may serve as therapeutic targets for disease management.

Neuron-specific enolase in nasal secretions as a novel biomarker of olfactory dysfunction in chronic rhinosinusitis.

Olfactory dysfunction is a diagnostic criterion for chronic rhinosinusitis (CRS). During chronic inflammation and olfactory neuronal damage in CRS, it is likely that neuron-specific enolase (NSE) can leak into nasal secretions (NS) and serum. Therefore, we postulated that NSE levels in NS and in circulation may be indicative of olfactory dysfunction in CRS. To evaluate the relationship between the NS and serum concentrations of NSE with olfactory dysfunction in subjects with CRS. The patients with CRS were classified into two groups, depending on the presence of polyps: CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). A group of age- and sex-matched healthy volunteers served as controls. Olfactory function assessment was performed by using Sniffin' Sticks. NSE concentrations in serum and NS were analyzed by using the enzyme immunometric assay kit specific for the γ subunit. The study included 46 patients with CRSsNP, 25 women (54.3%) and 21 men (45.7%), mean (standard deviation [SD]) age, 34.1 ± 12.3 years; and 54 patients with CRSwNP, 24 women (44.4%) and 30 men (55.6%), mean (SD) age, 37.9 ± 17.5 years. A group of 40 healthy volunteers who were matched for age and sex served as controls. Significantly higher serum and NS levels of NSE were measured in patients with CRS compared with healthy controls (p < 0.001). In the CRSwNP group, both mean (SD) serum (83.5 ± 37.6 ng/mL) and mean (SD) NS (6.1 ± 2.3 ng/mL) levels of NSE were significantly higher than in the CRSsNP group (46.4 ± 7.3 ng/mL [p < 0.001] and 1.7 ± 0.5 ng/mL [p < 0.001], respectively). In both the CRSsNP and CRSwNP groups (but not in the healthy controls), significant negative correlations between NS NSE levels and TDI scores (r = -0.63, p < 0.001 for the CRSwNP group, and r = -0.51, p < 0.001 for CRSsNP group) were observed, which meant that higher NSE was associated with worse olfactory function. The study demonstrated a contribution of CRS to NSE and olfactory dysfunction.

Expression of YKL-40 and TLR4 in patients with chronic rhinosinusitis

To explore the expression of YKL-40, TLR4 and NF-κB in chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP and CRSsNP), and to investigate their expressional correlation and the potential role in pathogenesis of CRS. The specimens were obtained from sinus mucosa and inferior turbinate mucosa of the patients with informed consent. The different expression of YKL-40, TLR4 and NF-κB among each group was detected by real time RT-PCR and immunohistochemistry (S-P method). SPSS 17.0 software was used to analyze the data. mRNA level: The relative expression of YKL-40 in CRSwNP group (0.91±0.17) was higher than those in the control group (0.49±0.09), the difference was significant (t=2.12, P<0.05). The relative expression of TLR4 in CRSsNP group (0.88±0.19) and CRSwNP group (0.67±0.13) were lower than those in control group (1.48±0.14), the differences were significant (t value was -4.11, -2.48, all P<0.05). The relative expression of NF-κB in CRSsNP group (0.69±0.13) and CRSwNP group (0.72±0.14) were lower than those in control group (1.20±0.15), the differences were significant (t value was 2.33, 2.27, all P<0.05). Protein level: The expression of YKL-40 in CRSwNP group was stronger than that in CRSsNP group and control group (U value was 72.5 and 73, all P<0.01). The expression of TLR4 in CRSwNP group and CRSsNP group was weaker than that in control group (U value was 62 and 38, all P<0.01). There was a negative correlation between YKL-40 and TLR4 (rmRNA=-0.741, P<0.01; rprotein=-0.46, P<0.05) in CRSwNP group. The expression of YKL-40 in pantients with CRSwNP is higher than those in healthy control and CRSsNP patients. There was a negative correlation between YKL-40 and TLR4. Both of them may be involved in the pathogenesis of CRSwNP.

Association of common filaggrin null mutations with atopy but not chronic rhinosinusitis

Association of common filaggrin null mutations with atopy but not chronic rhinosinusitis

The importance of local eosinophilia in the surgical outcome of chronic rhinosinusitis: a 3-year prospective observational study.

Patients with chronic rhinosinusitis with/without nasal polyps (CRSwNP/CRSsNP) benefit from endoscopic sinus surgery (ESS), with an estimated success rate of 80%. At present, the influence on clinical outcome after ESS of eosinophils, eosinophilic mucin (EM), and fungal hyphae (FH) in secretions remains unclear. By delineating CRS groups and subgroups based on the finding of eosinophils, EM, and FH, differences in recurrence after ESS were investigated. A prospective monocenter study including 221 CRS patients who were unresponsive to medical treatment and underwent ESS was performed. All tissue and sinonasal secretions were microscopically examined for the presence of eosinophils, EM, and FH. Patients were followed for 3 years after surgery. Recurrence was defined according to the European position paper on rhinosinusitis and nasal polyps. In total, 96 CRSwNP and 125 CRSsNP patients were included. Tissue eosinophils were found in 78% of CRSwNP patients compared with 42% in CRSsNP patients. EM was observed in 52% of the CRSwNP group versus 20% of the CRSsNP group. Furthermore, secretion analysis revealed FH in 7% of CRS. Recurrence in the total group was 22% over 3 years. CRSwNP patients with tissue eosinophilic involvement showed a recurrence rate of 48%, and those with additional EM showed recurrence in 56%. The presence of eosinophils in tissue or airway secretions greatly increases the risk of recurrent disease in CRSwNP patients. The finding of tissue eosinophilia and EM provides valuable information regarding the increased likelihood of CRS recurrence after ESS, whereas the finding of FH does not.

Long‐term control in chronic rhinosinusitis after endoscopic sinus surgery

The concept of control of chronic rhinosinusitis (CRS) has only recently been introduced by the EPOS expert panel following the concept of control in allergic rhinitis and asthma. The aim of this study was to examine the degree of control of CRS at a mean period of 3-5 years after endoscopic sinus surgery (ESS) and to correlate the new criteria of control of CRS to VAS (visual analogue scores) for sinonasal symptoms and the SNOT-22 questionnaire. Another aim was to find out if patients changed from controlled to partly controlled or uncontrolled following nasal endoscopy. All adult patients who had a bilateral ESS procedure for bilateral inflammatory sinonasal disease at the University Hospitals Leuven between January 2008 and December 2010 were contacted by classic mail. They were asked to complete a survey including sinonasal symptoms according to EPOS criteria, VAS scores, SNOT-22 and SF-36 questionnaires and general questions regarding asthma, smoking habits, allergies and current medication intake. They were invited to the out-patient clinic for nasal endoscopy. The response rate was 54.5% (n = 297). 19.8% were well controlled, 39.3% partly and 40.9% uncontrolled. There was no significant difference between the CRSwNP and CRSsNP groups. These results only depended on the self-reported symptoms, without taking into consideration endoscopic examination. Sixty patients underwent endoscopic examination of which 10% were controlled, 30% partly and 60% uncontrolled. The results of the examination showed that 18 patients had signs of recurrence (30%). In 77.8%, the endoscopic findings did not change the degree of control as defined by the questionnaire. 16.7% changed from partly to uncontrolled and 5.6% from controlled to partly controlled. The average global VAS scores of the controlled, partly and uncontrolled groups were 0.8, 2.7 and 5.7 respectively. The average SNOT-22 scores were 9.7, 22.2 and 44.8 respectively. The percentage of partly and uncontrolled CRS greatly overshadows the 19.8% of well controlled CRS. In 77.8% of cases, endoscopic investigation did not change the degree of self-reported control. The sensitivity of the EPOS questionnaire is 94.4% and the specificity is 14.3%. Therefore, endoscopy is useful in lowering the number of false positives. However, as the goal of treatment is the control of symptoms, the value of nasal endoscopy in defining control is one that is debatable.

Polymorphisms in RYBP and AOAH Genes Are Associated with Chronic Rhinosinusitis in a Chinese Population: A Replication Study

BackgroundThe development of CRS is believed to be the result of combined interactions between the genetic background of the affected subject and environmental factors.ObjectivesTo replicate and extend our recent findings from genetic association studies in chronic rhinosinusitis (CRS) performed in a Canadian Caucasian population in a Chinese population.MethodsIn a case-control replication study, DNA samples were obtained from CRS with (n = 306; CRSwNP) and without (n = 332; CRSsNP) nasal polyps, and controls (n = 315) in a Chinese population. A total of forty-nine single nucleotide polymorphisms (SNPs) selected from previous identified SNPs associated with CRS in Canadian population, and SNPs from the CHB HapMap dataset were individually genotyped.ResultsWe identified two SNPs respectively in RYBP (rs4532099, p = 2.15E–06, OR = 2.59) and AOAH (rs4504543, p = 0.0001152, OR = 0.58) significantly associated with whole CRS cohort. Subgroup analysis for the presence of nasal polyps (CRSwNP and CRSsNP) displayed significant association in CRSwNP cohorts regarding to one SNP in RYBP (P = 3.24E–006, OR = 2.76). Evidence of association in the CRSsNP groups in terms of 2 SNPs (AOAH_rs4504543 and RYBP_rs4532099) was detected as well. Stratifying analysis by gender demonstrated that none of the selected SNPs were associated with CRSwNP as well as CRSsNP. Meanwhile 3 SNPs (IL1A_rs17561, P = 0.005778; IL1A_rs1800587, P = 0.009561; IRAK4_rs4251513, P = 0.03837) were associated with serum total IgE level.ConclusionsThese genes are biologically plausible, with roles in regulation of transcription (RYBP) and inflammatory response (AOAH). The present data suggests the potential common genetic basis in the development of CRS in Chinese and Caucasian population.

Clinical Characteristics of Patients with Chronic Rhinosinusitis and Specific Antibody Deficiency

RationaleSpecific antibody deficiency (SAD) is characterized by an inadequate polysaccharide vaccine response and is considered in patients with chronic rhinosinusitis (CRS). There is limited data on patients with CRS and SAD. We assessed the clinical characteristics, comorbidities and outcomes of these patients.MethodsWe reviewed the electronic database records of patients with CRS who were evaluated for immunodeficiency with quantitative immunoglobulins or pneumococcal antibody titers checked pre- and post-Pneumovax® between 2002 and 2011. The subjects’ clinical and laboratory results were assessed.ResultsOf 528 subjects with CRS, 149 (28%) had CRS with nasal polyps (CRSwNP) and 379 (72%) had CRS without nasal polyps (CRSsNP). Of the 247 subjects evaluated for SAD, 50 (20%) had an inadequate response to the vaccine (10 of 68 [15%] in the CRSsNP group and 40 of 179 [22%] in the CRSwNP group). Nonresponders had significantly lower IgG levels, although within normal range (>700 mg/dL), compared with responder and normal baseline subjects (874.0±308.2 vs. 956.7±212.4 vs. 1022.5±281.0, p<0.01). Nonresponders received more antibiotics courses relative to responders in the two years following Pneumovax® (3.12±2.52 vs. 2.30±2.42, p<0.05). CRSsNP asthmatics had significantly lower post-immunization titers compared to CRSsNP non-asthmatics (9.17±3.28 vs. 7.49±3.585, p<0.05). Eleven nonresponders (22%) received immunoglobulin (Ig) replacement therapy.ConclusionsOf 247 CRS patients evaluated for immunodeficiency, 20% had SAD. On average, those with SAD received more courses of antibiotics than those without. Eleven patients with SAD (22%) received Ig therapy over an eight-year time period, suggesting that a majority of these patients do not need Ig therapy. RationaleSpecific antibody deficiency (SAD) is characterized by an inadequate polysaccharide vaccine response and is considered in patients with chronic rhinosinusitis (CRS). There is limited data on patients with CRS and SAD. We assessed the clinical characteristics, comorbidities and outcomes of these patients. Specific antibody deficiency (SAD) is characterized by an inadequate polysaccharide vaccine response and is considered in patients with chronic rhinosinusitis (CRS). There is limited data on patients with CRS and SAD. We assessed the clinical characteristics, comorbidities and outcomes of these patients. MethodsWe reviewed the electronic database records of patients with CRS who were evaluated for immunodeficiency with quantitative immunoglobulins or pneumococcal antibody titers checked pre- and post-Pneumovax® between 2002 and 2011. The subjects’ clinical and laboratory results were assessed. We reviewed the electronic database records of patients with CRS who were evaluated for immunodeficiency with quantitative immunoglobulins or pneumococcal antibody titers checked pre- and post-Pneumovax® between 2002 and 2011. The subjects’ clinical and laboratory results were assessed. ResultsOf 528 subjects with CRS, 149 (28%) had CRS with nasal polyps (CRSwNP) and 379 (72%) had CRS without nasal polyps (CRSsNP). Of the 247 subjects evaluated for SAD, 50 (20%) had an inadequate response to the vaccine (10 of 68 [15%] in the CRSsNP group and 40 of 179 [22%] in the CRSwNP group). Nonresponders had significantly lower IgG levels, although within normal range (>700 mg/dL), compared with responder and normal baseline subjects (874.0±308.2 vs. 956.7±212.4 vs. 1022.5±281.0, p<0.01). Nonresponders received more antibiotics courses relative to responders in the two years following Pneumovax® (3.12±2.52 vs. 2.30±2.42, p<0.05). CRSsNP asthmatics had significantly lower post-immunization titers compared to CRSsNP non-asthmatics (9.17±3.28 vs. 7.49±3.585, p<0.05). Eleven nonresponders (22%) received immunoglobulin (Ig) replacement therapy. Of 528 subjects with CRS, 149 (28%) had CRS with nasal polyps (CRSwNP) and 379 (72%) had CRS without nasal polyps (CRSsNP). Of the 247 subjects evaluated for SAD, 50 (20%) had an inadequate response to the vaccine (10 of 68 [15%] in the CRSsNP group and 40 of 179 [22%] in the CRSwNP group). Nonresponders had significantly lower IgG levels, although within normal range (>700 mg/dL), compared with responder and normal baseline subjects (874.0±308.2 vs. 956.7±212.4 vs. 1022.5±281.0, p<0.01). Nonresponders received more antibiotics courses relative to responders in the two years following Pneumovax® (3.12±2.52 vs. 2.30±2.42, p<0.05). CRSsNP asthmatics had significantly lower post-immunization titers compared to CRSsNP non-asthmatics (9.17±3.28 vs. 7.49±3.585, p<0.05). Eleven nonresponders (22%) received immunoglobulin (Ig) replacement therapy. ConclusionsOf 247 CRS patients evaluated for immunodeficiency, 20% had SAD. On average, those with SAD received more courses of antibiotics than those without. Eleven patients with SAD (22%) received Ig therapy over an eight-year time period, suggesting that a majority of these patients do not need Ig therapy. Of 247 CRS patients evaluated for immunodeficiency, 20% had SAD. On average, those with SAD received more courses of antibiotics than those without. Eleven patients with SAD (22%) received Ig therapy over an eight-year time period, suggesting that a majority of these patients do not need Ig therapy.