Direct economic burden 1 year postoperation in Chinese adult patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a common and challenging clinical entity, and its economic burden has not been well described in China thus far. METHODS: A total of 101 CRSwNP patients who underwent endoscopic sinus surgery were included to investigate direct costs in the first year post-surgery. Costs for outpatient visits, medication use, and examination costs were obtained from the Hospital Information System, and differences were compared between subgroups. Multiple linear regression analysis was adopted to investigate the main influencing factors on annual total direct costs for CRSwNP patients. RESULTS: Ninety-two subjects completed the study. The individual mean total direct cost for a CRSwNP patient 1 year post-surgery was $742.4. The largest contributors were pharmacy costs ($580.2), followed by examination costs ($108.1) and outpatient visits ($54.1). Total direct costs were higher in subgroups of patients with uncontrolled clinical status, asthma comorbidity, and eosinophilic CRSwNP compared to their counterparts. The main influencing factors were clinical control status (P = 0.016) and asthma comorbidity (P = 0.035). CONCLUSIONS: The individual mean total direct cost of CRSwNP in 1-year post-surgery was $742.4. Clinical control status and asthma comorbidity influence these costs and are therefore important in guiding health resources allocation for CRSwNP management.

Gene Expression Analysis by Real-Time PCR in Nasal Brushings of Adult Patients with Allergic Rhinitis, Suspected Allergic Rhinitis, and Nonallergic Rhinitis.

BACKGROUND: Epithelial gene expression in allergic rhinitis patients has been evaluated by microarray. However, gene expression in patients with nonallergic rhinitis and suspected allergic rhinitis who reported allergen-related nasal symptoms but presented a negative atopic test was unknown. OBJECTIVES: The aim of this study was to observe and compare epithelial gene expression in patients with allergic rhinitis, suspected allergic rhinitis, and nonallergic rhinitis. METHODS: Nasal brushings were collected from healthy controls and from patients with allergic rhinitis, suspected allergic rhinitis, and nonallergic rhinitis. The expressions of 20 genes selected from a previous microarray study were measured by real-time PCR. Associations of these genes with allergen type, disease duration and severity, the grade of nasal smear eosinophilia, and serum total IgE were analyzed. RESULTS: Twelve genes were confirmed to be upregulated in current adult allergic rhinitis patients allergic to multiple allergens, and 10 of them were also increased in the suspected allergic rhinitis and nonallergic rhinitis groups. TFF3 and ITLN1 expressions were increased in allergic rhinitis and suspected allergic rhinitis, but not nonallergic rhinitis. Different expressions between the allergic rhinitis and nonallergic rhinitis groups were found for 3 genes: CST1, TFF3, and ITLN1. In the allergic rhinitis patients, all 12 genes were upregulated in the seasonal and perennial groups; 9 of these 12 genes were also upregulated in the mixed group. In suspected allergic rhinitis patients, all 12 genes were upregulated in the perennial group; 8 of these 12 genes were also upregulated in the seasonal group and only 5 in the mixed group. No gene expression was associated with disease duration and serum total IgE. GCNT3 was positively correlated with the grade of nasal smear eosinophilia in the suspected allergic rhinitis group. Different genes were found to be associated with disease severity in different rhinitis groups. CONCLUSIONS: Patients with allergic rhinitis, suspected allergic rhinitis, and nonallergic rhinitis showed much similarity with regard to epithelial gene expression; most genes were related to Th2 inflammation. CST1, TFF3, and ITLN1 might have the ability to differentiate allergic rhinitis from nonallergic rhinitis. Understanding the mechanisms underlying different types of rhinitis may be helpful for rhinitis diagnosis and treatment.

Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis.

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines-with a focus on China-will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.

Origin site-based staging system of sinonasal inverted papilloma for application to endoscopic sinus surgery.

BACKGROUND: We aimed to assess the recurrence risk of sinonasal inverted papillomas (SNIPs), based on a staging system developed according to the originating site of SNIP. METHODS: A total of 200 patients with SNIP were enrolled, and a staging system was developed based on the originating sites and corresponding recurrence rates of tumor in the patients. In the verification phase, 675 patients with SNIPs were enrolled as above, and the originating sites of the SNIPs were confirmed by an endoscopic sinus surgery. Cluster analysis was performed to determine the stage for each SNIP. RESULTS: Overall, 608 patients completed the study. SNIP recurrence rates for stages 1-4 were 0 (n = 43), 4.0% (n = 420), 13.4% (n = 134), 36.4% (n = 11), respectively (total = 6.4%). CONCLUSIONS: The origin site-based classification of SNIP may aid surgeons in selecting appropriate endoscopic surgical approaches to minimize the risk of recurrence.

Recent advances in the diagnosis of allergic rhinitis.

INTRODUCTION: Allergic rhinitis (AR) is a disorder with high prevalence worldwide. Identification of clinically relevant allergens is the key step for the diagnosis, allergen avoidance and allergen specific immunotherapy for AR. Areas covered: With the new findings of mechanisms of AR and the development of technology, much progress has been achieved in the diagnosis of AR recently. We review the recent advances about local IgE, in vivo and in vitro tests, cytological diagnosis and nitric oxide (NO) in the diagnosis of AR. Expert commentary: AR is traditionally diagnosed with the combined evaluation of history and allergen sensitization by in vivo skin prick tests and in vitro allergen specific IgE in serum, to confirm the correlation between clinical history and potential allergens. Nasal provocation test and local IgE measurement can be used to diagnose local AR. Allergen microarray has the ability to detect more potential allergens. Basophil activation and mast cell activation tests can be used in allergen diagnosis and to modify the response to immunotherapy, while cytological diagnosis is useful in the differential diagnosis of AR and non-AR. Nasal NO has been confirmed to be an optimal biomarker to discriminate between AR and non-AR.

Diagnostic Value of Nasal Cytology in Chronic Rhinosinusitis Assessed by a Liquid-based Cytological Technique.

Back ground: Nasal cytology has generally been employed as a useful diagnostic tool in the differentiation of rhinopathies. Objective The aim of this study was to assess the extent and diagnostic value of inflammation of nasal and paranasal sinus mucosa in chronic rhinosinusitis patients by employing a combination of nasal brushings and a liquid-based cytological technique. Methods Forty-eight patients with chronic sinusitis and 20 control subjects without any sign of sinusitis undergoing endoscopic surgery, although not all underwent endoscopic sinus surgery, were recruited to the study. Nasal cytology samples were collected from all subjects using nasal brush and processed a liquid-based cytological technique for evaluation of total and differential inflammatory cell counts. Biopsies were also taken from the inferior turbinates from its anterior margin in all subjects and from identical lateral maxillary sinus mucosa in patients with chronic sinusitis during surgery and routinely processed for staining and evaluation of inflammatory cells. Results Total and individual inflammatory cell counts in nasal brushings were significantly correlated with the respective inflammatory cell counts in biopsies obtained from the inferior turbinate (eosinophils: r = .519 and P = .016; neutrophils: r = .540 and P = .012; lymphocytes: r = .540 and P = .011) but not in biopsies obtained from the maxillary sinus. No correlation was observed between the inflammatory cells in biopsies from the inferior turbinate and biopsies from the maxillary sinus. The liquid-based cytological technique showed higher sensitivity (94.1%), specificity (76.9%), and positive predictive value (84.2%) for inflammation in the inferior turbinates than for inflammation in the maxillary sinus (sensitivity = 63.4% and positive predictive value = 63.4%). Conclusion Nasal cytology evaluated by use of nasal brushings processed by a liquid-based cytological technique is likely to have higher diagnostic value for the inflammatory response in noninfectious rhinitis than in chronic rhinosinusitis.

Photoinduced Formation of Peroxide Ions on La2O3 and Nd2O3 under O2: Effects of Excitation Wavelength and Crystal Structure.

Photoinduced formation of peroxide ions on La2O3 and Nd2O3 under O2 was studied by in-situ microprobe Raman spectroscopy with attention focused on the effect of excitation wavelength and crystal structure on the O2(2-) formation. It was found that photoexcitations at 633, 532, 514, and 325 nm can induce O2(2-) formation over La2O3 at 450 °C. By contrast, photoexcitation at 785 nm does not cause formation of O2(2-) up to 500 °C. Photoexcitation at 325 nm can induce O2(2-) formation on cubic Nd2O3 at 25 °C, but cannot induce O2(2-) formation on hexagonal Nd2O3 up to 200 °C. The significant difference in the behavior of O2(2-) formation over the Nd2O3 samples of the two structures can be related to the difference in the capacity to adsorb O2. Since the number of oxygen vacancies in cubic Nd2O3 is larger than that in the hexagonal one, the former has a higher capacity than the latter to adsorb O2. As a result, cubic Nd2O3 is more favorable to the reaction of O2 with O(2-) to generate O2(2-). The structural similarity between cubic Nd2O3 and Nd2O2(O2) may be another factor in favor of peroxide formation.

[Long-term efficacy of Dermatophagoides pteronyssinus immunotherapy in patients with allergic rhinitis: a 3-year prospective study].

OBJECTIVE: To evaluate the long-term efficacy of subcutaneous immunotherapy with Dermatophagoides pteronyssinus (DerP) in patients with allergic rhinitis. METHODS: Ninety-two patients with allergic rhinitis to DerP were randomly allocated to receive either specific immunotherapy (n = 46) or medical treatment (n = 46). Symptom and medication scores and skin response to Derp were assessed to evaluate the clinical efficacy in the baseline and after three years treatment. DerP-specific IgE and IgG4 were measured. RESULTS: After three years treatment, the immunotherapy group showed sustained reductions in symptom scores (before treatment 9.20 [7.50;11.13], after treatment 3.32 [2.49;5.12], Z = -5.13, P < 0.05), medication scores (before treatment 0.72 [0.47;0.83], after treatment 0.31 [0.28;0.45], Z = -5.78, P < 0.05) and specific skin response to Derp (t = 6.37, P < 0.05) when compared with control group. There were no differences in the level of serum specific IgE before and after three-year treatment (before treatment 16.32 [4.34;38.65] kU/L, after treatment 15.85 [4.93;46.27] kU/L, Z = -0.84, P > 0.05), but the level of serum specific IgG4 increased significantly after one year treatment in immunotherapy group (before treatment 486 [319;1439] AU/L, after treatment 8387 [7732;16 634] AU/L, Z = -2.81, P < 0.05). After three-year treatment, 7.5% (3/40) of patients had asthma in immunotherapy group compared to 27.8% (10/36) in the control group (χ(2) = 5.50, P < 0.05), and 15.0% of the initially DerP nonsensitized patients in immunotherapy group had developed new sensitization compared to 47.2% in the control group (χ(2) = 9.32, P < 0.05). CONCLUSION: Three years immunotherapy improves allergic rhinitis symptoms, increases the level of serum specific IgG4, reduces the development of asthma and new sensitization.

Histological differences between the mucosa on the medial and lateral sides of the normal uncinate process.

OBJECTIVES/HYPOTHESIS: To determine whether histological differences exist between the medial and lateral sides of the normal mucosa of the uncinate process (UP). STUDY DESIGN: Retrospective histological analysis. METHODS: Twenty UPs from the nasal cavities of 17 patients with no evidence of sinus disease were harvested during endoscopic sinus surgery. The dissected mucosa was stained with hematoxylin and eosin, chromotrope 2R, alcian blue-periodic acid-Schiff, and toluidine blue. RESULTS: : The thickness of the nasal mucosa was significantly greater on the medial side of the UPs than on the lateral side (173 +/- 72 microm vs. 157 +/- 14 microm). The thickness of the basement membrane of the lamina propria of the mucosa was significantly greater on the medial side of the UPs than on the lateral side (2.8 +/- 2.5 microm vs. 0.8 +/- 1.0 microm). The thickness of the epithelium was greater on the lateral side than on the medial side (14 +/- 3 microm vs. 12 +/- 3 microm). The area of mucous glands was larger on the medial side than on the lateral side (43 +/- 13 x 10(-2) mm(2) vs. 33 +/- 12 x 10(-2) mm(2)). Meanwhile, the number of mast cells (4.0 +/- 1.2 vs. 1.8 +/- 0.2) and goblet cells (23.1 +/- 12.3 vs. 10.5 +/- 10.2) were both found to be higher on the lateral side than on the medial side. CONCLUSIONS: There are histological differences between the mucosa on the medial and lateral sides of the normal UP.

Association of the CD14 gene polymorphism C-159T with allergic rhinitis.

BACKGROUND: Altered expression of the cluster differentiation antigen, CD14, may affect the proportion of T-helper type 1 (Th1) to Th2 cells, thereby influencing the immunoglobulin E (IgE) response and associated inflammatory phenotype in allergic conditions. Therefore, the gene encoding CD14 is considered as a positional candidate gene for atopy. Recently, a functional C-159 T polymorphism has been described in the promoter region of the gene and has been associated with increased gene expression and atopic phenotypes in various ethnic populations. We evaluated the relationship between the C-159 T polymorphism in the promoter of the CD14 gene and the total serum IgE level in Chinese adult patients with allergic rhinitis. METHODS: Polymerase chain reaction with restriction fragment length polymorphism (RFLP) analysis was used to determine the C-159 T polymorphism in subjects with allergic rhinitis (n = 92) and nonallergic disease controls (n = 72). Total serum IgE was also measured. RESULTS: In the allergic rhinitis group, the frequency of the TT homozygotes was significantly higher than for the control group (p < 0.05). In both groups, the C-159 T polymorphism is not associated with serum IgE levels. CONCLUSION: TT homozygotes are more common in adult patients with allergic rhinitis among the Chinese population.

Remodeling of nasal mucosa by allergen exposure in guinea pigs is suppressed by steroid and pranlukast.

BACKGROUND: It is unclear whether remodeling exists in allergic rhinitis in man. The aim of this study was to establish a guinea pig model of allergic rhinitis with remodeling and to examine the effects of dexamethasone and pranlukast on nasal mucosa remodeling. METHODS: In the first experiment, three groups of ovalbumin-sensitized Hartley guinea pigs received intranasal challenges with ovalbumin for 1, 8, 12 weeks, respectively. In the second experiment, to examine the effect of dexamethasone and pranlukast, the animals were divided into 4 groups: negative control group; ovalbumin-sensitized group; ovalbumin + dexamethasone group; and ovalbumin + pranlukast group. During 12 weeks of intranasal exposure to ovalbumin, the latter two groups received daily intraperitoneal injections of dexamethasone and pranlukast, respectively. RESULTS: In the first experiment, in contrast to the negative control group, the ovalbumin-sensitized group exhibited significant goblet cell hyperplasia, epithelial damage and deposition of extracellular matrix in the nasal septal mucosa and conchae. In the second experiment, these changes were significantly inhibited by dexamethasone and pranlukast, respectively. CONCLUSIONS: We have established a model of upper airway remodeling in guinea pigs. The tissue remodeling was inhibited by early intervention with the antiallergic-inflammatory agents dexamethasone and pranlukast.

[Association of single nucleotide polymorphisms of GATA3 with allergic rhinitis phenotypes in Chinese].

OBJECTIVE: To evaluate the association between single nucleotide polymorphisms (SNP) of GATA3 and Chinese with allergic rhinitis. METHODS: This study included 109 patients with allergic rhinitis and 112 healthy control people. SNP of two loci with restriction fragment length polymorphism was detected, rs1269486 at promoter region and rs2229360 located 92 bp downstream of STOP codon. Total IgE and specific IgE of Der p and Der f with different genotypes of the two loci were compared. RESULTS: There was SNP at both loci of rs1269486 and rs2229360. The genotypes of rs1269486 were GG, GA and AA, and the genotypes of rs2229360 were CC, CT and TT. The frequency of genotype GG and allele G in patient group was significantly higher than that in control group (chi2 = 13.75, P <0.01; chi2 = 12.91, P <0.01), and the frequency of genotype GA and allele A in patient group was significantly lower than that in control group (chi2 = 11.90, P <0.01; chi2 =12.91, P <0.01). There were no significant differences between patient group and control group for the frequencies of genotypes and alleles at rs2229360 (P > 0.05). The haplotype frequency of GC in patient group was significantly higher than that in control group (chi2 = 114.59, P < 0.01), and the haplotype frequency of AC in patient group was significantly lower than that in control group (chi2 = 87.52, P <0.01). There was no significant difference of the levels of serum total IgE and specific IgE to Der p and Der f with the genotypes at the two loci (P >0.05). CONCLUSIONS: The SNP at rs1269486 of GATA3 is associated with allergic rhinitis in Chinese.

[Effect of Pranlukast on tissue remodeling in experimental guinea pig allergic rhinitis model].

OBJECTIVE: To explore the impact of Pranlukast in nasal mucosal remodeling in experimental allergic rhinitis. METHODS: Fourteen male guinea pigs were randomly divided into 3 groups: control group, ovalbumin (OVA) group and OVA + Pranlukast group. In the OVA group and OVA + Pranlukast group, OVA sensitized Hartley guinea pigs were exposured intranasally to OVA for a total of 12 weeks, the OVA + Pranlukast group received additional Pranlukast treatment from the second week to the 12th week. Paraffin embedded sections were stained with hematoxylin and eosin (HE), alcian blue-periodic acid-Schiff (AB-PAS), and Masson's Trichrome (MT). Infiltrating eosinophils, the number of goblet cells in the surface epithelium and gland cells in subepithelial nasal septal mucosa were counted. The damage of epithelium in nasal septum and extracellular matrix of nasal septal mucosa and conchae were determined. RESULTS: Compared with the control, the prolonged OVA exposure protocol caused significant pathological changes in the nasal mucosa, which included eosinophils infiltration into epithelium and submucosa (106.90 +/- 13.66), significant goblet hyperplasia (22.05 +/- 5.81/mm), epithelial damage (intact epithelium: 47.25% +/- 7.67%) and deposition of extracellular matrix. These changes were significantly inhibited by Pranlukast, in which group, there were few eosinophils(8.95 +/- 2.32) , few goblet cells (5.73 +/- 1.07/mm), and relative intact epithelium (intact epithelium: 83.15% +/- 8.05%), and no significant ECM deposition. CONCLUSIONS: Early Pranlukast intervention could inhibit nasal mucosal remodeling in allergic rhinitis.

[Nasal mucosa remodeling in guinea pig model of allergic rhinitis].

OBJECTIVE: To explore the feature of nasal mucosa remodeling in experimental allergic rhinitis. METHODS: Twenty-four male Hartley guinea pigs (4 weeks, 250 -300 g) were randomly divided into four groups (control group and allergen exposure groups 1 - 3), each group had 6 guinea pigs. Allergen exposure animals were sensitized by intraperitoneal (ip) injection of ovalbumin (OVA). Sensitized guinea pigs were subjected to either brief or prolonged exposure to allergen. Both brief exposure group (allergen exposure groups) and prolonged exposure group (allergen exposure group 2 and 3) received a daily intranasal challenge with 5% OVA in 0.9% saline from Day 22 to Day 28, the prolonged exposure group (allergen exposure group 2 and 3) followed by twice weekly exposure to 5% OVA intranasal for an additional 8 and 12 weeks respectively. Control animals were given saline only. At 24 h after the last intranasal challenge, the guinea pigs were killed and the heads of the animals were removed and fixed in 10% neutral buffered formalin for 24 hours, then decalcified in 5% trichloroacetic acid for 10 days. The tissue blocks were embedded in paraffin. The paraffin sections 3 microm thick were stained with hematoxylin and eosin (HE), alcian blue (pH, 2. 6)-periodic acid-Schiff (AB-PAS), and Masson's Trichrome (MT). The infiltrating eosinophils in nasal mucosa were examined, AB-PAS-positive cells in the surface epithelium in nasal septal mucosa were counted. The percentage area of MT stained extracellular matrix in septal mucosa and conchae and damage of epithelium were determined by an image analyzer. RESULTS: The control group only presented a few eosinophils. Significant eosinophil infiltration was observed in the sensitized groups. Compared with control group (intact epithelium 87.7% +/- 11.1%), there was no significant epithelial damage in 1 week exposure group. Significant epithelial damage were observed in 8 and 12 weeks groups (intact epithelium 36.7% +/- 16.9%, 37.9% +/- 12.9%, respectively). An increase in AB-PAS-positive cells was observed in the mucosa of nasal septum in the prolonged allergen exposure groups, but not in the brief allergic inflammation group in comparison with the control. The brief OVA exposure group did not show increased collagen fibrils within the mucosa of nasal septum and conchae. In contrast, after prolonged OVA exposure an increase in matrix was observed. Furthermore, in both the nasal septum and conchae, significant increasing of ECM deposition was found in a further prolonged exposure for 12 weeks compared to 8 weeks. CONCLUSIONS: Epithelial damage, goblet cells hyperplasia and extracellular matrix deposition were observed as the features of remodeling in this guinea pig model of allergic rhinitis.

[Immunoregulatory effect of Bacillus Calmette Guerin aerosol to allergic airway diseases].

OBJECTIVE: To investigate whether bacillus calmette guerin (BCG) is effective used transairway and its preventive mechanisms to allergic airway diseases. METHODS: Animal experiment was finished. Adult rats were devided into four groups: control group, ovalbumin-sensitized group, BCG used transairway group, BCG used transairway + ovalbumin-sensitized group. Then these animals symptoms were studied and the pathology change were studied under microscope about nasal and bronchi mucosa and bronchoalveolar lavege fluid cells. IL-4 mRNA and IFN-gamma mRNA in lung tissue were detected through RT-PCR, the protein production of IL-4 and IFN-gamma about bronchoalveolar lavege fluid and serum were detected through ELISA. RESULTS: In ovalbumin-sensitized group, allergic animal model were made successfully. In only BCG used transairway group, the symptoms of animals were normal, few inflammation cells infiltrated into the mucosa of nasal and bronchi, the numbers of macrophage were greatly increased in smear of bronchoalveolar lavege fluid, IFN-gamma mRNA and protein production were greatly increased. In BCG used transairway + ovalbumin-sensitized group, the allergic symptoms and inflammation were greatly reduced, not only IFN-gamma mRNA and protein production were increased but also IL-4 mRNA and protein production were greatly decreased. CONCLUSION: It is a good pathway that BCG used transairway. The immunoloregulation mechanisms of BCG to allergic airway diseases are to enhance Th1 response, in the meantime, to suppress Th2 response.