Chapter 2. Inflammatory Cell Patterns in Nasal Polyps and Chronic Sinusitis 2.1 Introduction Nasal polyps and chronic sinusitis are common related diseases worldwide. In chapter 1, the epidemiology and pathogenesis of these diseases was briefly reviewed. They are multifactorial diseases closely related with asthma,1,2 aspirin intolerance,3 cystic fibrosis,4 rhinitis and especially nonallergic rhinitis,5,6 immunodeficiency,7 primary ciliary dyskinesia,8,9 and other underlying diseases. Although many theories have been suggested, the roles of allergy and infection remain the most important and controversial underlying mechanisms in nasal polyp and chronic sinusitis. In addition, although the two diseases are concomitant in many patients, the pathogenic mechanism interlinking these two common nasal diseases is still incompletely understood. Most of the studies in nasal polyp and chronic sinusitis were carried out in Caucasians. In Asia, data on their etiology and pathophysiology are still lacking. Previous studies suggested that the respective epidemiology and aspects may differ in the Caucasian and Asian populations. The incidence rate of nasal polyps in Caucasians was reported to be 1% to 4.3%.10-14 The estimated prevalence of sinusitis in Europe and US ranges from 10% to 40%.15-17 However, in a national survey in Korea reported by Min et al.,18 the incidence rate of nasal polyps and chronic sinusitis was 0.5% and 1.01%, respectively. Etiology factors may also play various roles in different populations. For 135 example, cystic fibrosis, a common associated disease with nasal polyps and chronic sinusitis, is rare in Asian populations and the use of aspirin is also not as common as that in western countries. It was also suggested that chronic sinusitis in Asian populations had a higher incidence rate of nasal polyps than in Caucasians due to the narrower nasal passages.19 A difference in the pathogenesis of nasal polyps between Caucasians and Asians has also been suggested. As introduced in chapter 1, nasal polyps can be differentiated into four subgroups according to histophathology.20 Eosinophilic and neutrophilic nasal polyps are the two major subtypes which account for 85%-90% and 10% of the cases, respectively, in Caucasians.20 In Asians, a relatively higher incidence of neutrophilia (40%) and a relatively lower incidence of eosinophilia (41.7% to 65.2%) in nasal polyps have been suggested.21,22 However, a recent study by Lacroix et al.23 showed no major histological difference in nasal mucosa and polyp tissues obtained from African, Chinese and Caucasian patients. 2.2 Aim of Study 2.2.1 Hypothesis The underlying mechanism of chronic sinusitis and nasal polyps involves a complex inflammation characterized by infiltration and activation of various types of inflammatory cells. In this study, it is proposed that: I. The cell pattern and role of inflammatory cells in these diseases may differ depending on local and systemic triggering factors, i.e., allergy and infection. II. There exists an auxiliary effect between the unaffected and diseased nasal 136 mucosa in terms of inflammatory cells and cytokines leading to pathogenesis of the excised nasal polyps. This will help to explain the recurrent nature of nasal polyps. III. Not only eosinophils but also neutrophils and lymphocytes may play important roles in the persistence of mucosal inflammation and in inducing nasal airway remodeling. IV. There may be ethnic based differences controlling cell patterns involved in the chronic inflammation of nasal polyps and chronic sinusitis. 2.2.2 Specific Aims The specific aims of this study are: I. To study the type of cellular mechanisms and local tissue immune response in affected sinus mucosa and nasal polyp tissue using an immunohistochemical characterization of inflammatory cells and comparing these findings with that of normal nasal mucosa. II. To compare the spatial distribution of inflammatory cells in affected sinus mucosa/polyps with the biopsy specimens obtained from the uninvolved middle turbinate at the same site. The purpose of this comparison is to study the nature and localization of mucosal inflammation and the possibility of interactions between the two sites. III. To explore the relationship between the inflammatory cell pattern in sinus mucosa/polyps and clinical hypersensitivity and underlying diseases. 137 IV. To explore the ethnic based difference of chronic inflammation in nasal polyps and chronic sinusitis by comparing our results for local patients with those reported for Caucasian patients. This study allows for a better understanding of the pathogenic mechanisms of chronic sinusitis and nasal polyps. The results of this study will aid in the discovery of better-targeted therapies and preventive measures. In addition, the exploration of ethnic differences may suggest the contribution of genetic predisposition or environmental factors. 2.3 Methodology 2.3.1．Working Definitions Guidelines in the diagnosis of chronic sinusitis, nasal polyps, allergic rhinitis and atopy are: I. Chronic sinusitis Patients who present with following symptoms for 12 weeks or more: anterior and/or posterior mucopurulent drainage and nasal congestion. Nasal endoscopic examination shows discolored mucus or edema of the middle meatus or ethmoid area. Furthermore, a positive sinus CT scan with confirmation of mucosal disease is required. II. Nasal polyps Patients may have symptoms like stuffy nose, difficulty smelling odors and/or facial pain. Nasal endoscopic examination shows pale, semitranslucent, watery masses protruding into the nasal cavity. CT scan is used to determine the condition in 138 paranasal sinuses. Allergic rhinitis III. The occurrence of two or more symptoms (nasal obstruction, rhinorrea, sneezing and itchy nose) on most days during the past year. If patients coexisted with atopy, allergic rhinitis is diagnosed. Atopy IV. A positive serum specific IgE (equal or more than 0.35 IU/ml) to at least one of the inhalant allergens tested. 2.3.2 Study patients In this prospective study, patients with nasal polyps and chronic sinusitis, allergic rhinitis and non-atopic, non-rhinitis controls were randomly selected from the department of Otolaryngology, Head & Neck Surgery of the National University Hospital of Singapore as follows: I. Forty-eight patients, 34 males and 14 females, aged from 12 to 78 years (mean age 44) with unilateral/bilateral nasal polyps, who were scheduled for functional endoscopic sinus surgery. The diagnosis of nasal polyps was based on medical history and clinical examinations, including nasal endoscopic examination and CT scan. Among the above nasal polyp patients, six patients had available nasal polyp tissue, sinus mucosa as well as the paired middle turbinate. All of them were diagnosed as having nasal polyps with concomitant chronic sinusitis. They were four males and two 139 females, aged from 28 to 51 years (mean age 43). This small group was used for the exploration of any possible correlations between chronic sinusitis and nasal polyps. II. Twenty patients, ten males and ten females, aged from 19 to 76 years (mean age 47) with unilateral/bilateral chronic sinusitis but no nasal polyps, who were scheduled for functional endoscopic sinus surgery in our department. The diagnosis of chronic sinusitis was based on medical history and clinical examinations, including nasal endoscopic examination and CT scan. III. Fifteen patients, 14 males and one female, aged from 19 to 62 years (mean age 27) with allergic rhinitis who were scheduled for septal surgery in our department. Their atopy status was proved by the ImmunoCAP system (Pharmacia Diagnostics, Clayton, NC). These patients had no history of chronic sinusitis or nasal polyps. IV. A control group of fourteen non-rhinitis, non-atopic patients, 11 males and females, aged from 22 to 39 years (mean age 27), with septal deviation who were scheduled for septal plastic surgery. Patients with nasal polyps, sinusitis, allergic rhinitis and atopy were excluded. All subjects were specifically asked for a history of aspirin exposure and asthma. Patients with a history of paroxysmal attacks of breathlessness commonly associated with a tightness of the chest and wheezing were referred to the respiratory physician for further evaluation of asthma. All patients had a trial of an intranasal glucocorticosteroid spray but did not show a relief of their symptoms. Their medication was discontinued for more than one month prior to surgery.24,25 A signed 140 informed consent was obtained from the study patients before surgery. Approval to conduct this study was granted by the National Medical Research Council of Singapore and the institutional review board of the Medical Faculty of the National University of Singapore. Table 8. Patient groups in the study of inflammatory cell pattern. Patient group Mean age Number of patients Male/Female Nasal polyps 44 48 34/14 Chronic sinusitis 47 20 10/10 Allergic rhinitis 27 15 14/1 Control patients 27 14 11/3 2.3.3 Immunohistochemical study 2.3.3.1 Collecting Samples A pair of biopsies was taken, one from the nasal polyp/inflamed sinus mucosa and the other from the ipsilateral middle turbinate. One biopsy sample was taken from the middle turbinate of allergic rhinitis and control patients during septal plastic surgery. Specimens were embedded in a tissue-freezing medium (Leica Instruments GmbH) in liquid nitrogen immediately after resection. The frozen samples were kept at -80°C for further study. 2.3.3.2 Immunohistochemistry Staining26 Sections of µm were prepared in a cryostat and attached onto gelatinized slides and allowed to dry at room temperature overnight. The sections were fixed in pure acetone 141 for 10 minutes at 4°C followed by washing with PBS-TX (Phosphate-buffered saline with 0.1% Triton X-100, pH 7.4) times, for 10 minutes each. The slides were then incubated in 0.3% H2O2 for 30 minutes at room temperature to reduce nonspecific background staining due to endogenous peroxidase. After washing with PBS-TX again, the slides were incubated with 5% normal goat serum for hour at room temperature. Mouse anti-human monoclonal antibodies (Table 9) with appropriate dilution (1:200 to 1:100) were incubated overnight at 4°C for immunohistochemical staining. The next day, the slides were washed with PBS-TX and incubated with secondary antibody (BD Biosciences Parmingen, biotinylated polyclonal goat anti-mouse Ig with dilution of 1:300 in PBS) at room temperature for hour. After washing, ABC (avidin-biotin complex, DakoCytomation) was applied and incubated for hour at room temperature followed by another washing in PBS-TX. DAB (diaminobenzidine tetrahydrochloride, DakoCytomation) was used for color development for 5-10 minutes. After rinsing with distilled water, the sections were counterstained with Mayer’s hematoxylin (Sigma-Aldrich Corporate) for a further seconds, dehydrated with series ethanol (90%, 100%, 100%), and cleared with xylene (3 times), and mounted with a DePeX mounting medium (BDH Laboratory supplies). Control staining for nonspecific staining was routinely performed with PBS instead of primary antibodies, and all trials proved negative. To test the specificity of anti-CD4+ (helper T cells) and anti-CD8+ (cytotoxic/suppressor T cells), fresh human tonsil specimens were obtained. Consecutive samples were stained separately with anti-CD4, anti-CD8 and anti-CD3 antibodies (Lab Vision NeoMarker, Rabbit anti-human 142 monoclonal CD3, clone SP7) with the same protocol as mentioned above. The sum of CD4+ and CD8+ cells was approximated to the number of CD3+ cells. Table 9. Mouse anti-human monoclonal antibodies used. Antibody Manufacturer Clone Specificity Anti- CD4 DakoCytomation MT310 Helper/inducer T cells and subpopulation of macrophages Anti-CD8 DakoCytomation C8/114B Suppressor/cytotoxic T cells Anti-CD19 DakoCytomation HD37 Precursor and mature B cells (no plasma cells) Anti-CD1a DakoCytomation NA1/34 Langerhans cell Tryptase DakoCytomation AA1 Mast cell Neutrophil elastase DakoCytomation NP57 Neutrophil Major basic protein BD Biosciences AHE-2 Parmingen Eosinophil 2.3.3.3 Cell Counting Three areas with high intensity positive cell distribution were selected in each section and a cell count was performed under a light microscope at magnification of 400. The positive cells stained with peroxidase-labeled monoclonal antibody on cell membranes were counted. Cell counting was averaged and evaluated with scores from to 3.27,28 The counting was performed blindly without knowing the identity of the samples: 0: no positive staining cells; (+): A few (1-10) positive cells; 143 (++): A moderate number (11-20) of positive cells and some cluster of positive cells; (+++): Many (>20) positive cells. For CD4+ and CD8+ cells, additional absolute cell counts were performed. The mean numbers of cell counts in three power fields were calculated. 2.3.4 Allergy Test Table 10. Specific IgE interpretation.29 Quantitative Results ( kU/L) 100 Very high Three milliliters of peripheral blood was taken during surgery. Serum total IgE (tIgE) and specific IgE (sIgE) to a common panel of inhalant allergens, including Dermatophagoides pteronyssinus, Dermatophagoides farinae, Aspergillus fumigatus, cockroach, common pollen and ragweed mixtures (Bermuda grass, Ambrosia artemisiifolia, Ambrosia elatior) were determined using the ImmunoCAP system. Patients with sIgE ≥0.35 IU/ml to at least one of the testing allergens were considered as atopy. sIgE was classified into seven scores shown in Table 10. 144 characterized by chronic inflammation under the control of multi inflammatory cells, such as eosinopihls, CD8+ T cells and neutrophils, with lack of evidence for a contribution by IgE-mediated allergy. However, the development of chronic inflammation in the nasal and sinus cavities seems different. The inflammation in nasal polyps has a good correlation with that in the middle turbinate mucosa. It is in agreement with the widely accepted opinion that middle meatus is one of the most common sites of polyp origin. The development of chronic sinusitis, however, does not seem to occur under the same mechanism as that in middle turbinate mucosa. Whether sinusitis predisposes to or results from inflammation in the middle meatus and/or nasal polyp is not known. 2.8.4 Does Persistent Allergic Rhinitis Predispose for Nasal Polyps and Chronic Sinusitis? Allergic rhinitis is an inflammatory condition of the nasal mucosa induced by an IgE-mediated response. It can be classified into seasonal and perennial. Seasonal allergic rhinitis is usually correlated with aeroallergens especially outdoor allergens. Perennial allergic rhinitis is usually caused by sensitization to indoor aeroallergens, including dust mite, cockroach, animal dander, and in some regions, fungus. It has been suggested that the expression “intermittent” and “persistent” should be used instead of “seasonal” and “perennial” because of the commonly found polysesitizations.98 Intermittent allergic rhinitis is defined as symptoms lasting for less than four days per week and less than four weeks per year. Symptoms are mainly 240 pruritus, sneeze and discharge in these patients. In persistent allergic rhinitis, the symptoms last for more than four days per week or more than four weeks per year. Patients may mainly show stuffiness rather than sneeze and discharge. In clinics, persistent allergic rhinitis is more difficult to diagnose; and the diagnosis mainly depends on symptoms and atopic status proved by in vivo or in vitro tests. Singapore has a typical tropical climate. The temperature is constant throughout the year, fluctuating between 24°C to 32°C. The unique climate pattern here may provide different allergen profiles from other temperate regions. In the test of serum specific IgE of allergic rhinitis patients, the most commonly identified specific IgE were to Dermatophagoides pteronyssinus and Dermatophagoides farinae with a percentage of 100%, whereas specific IgE to common pollen and ragweed mixture was only 6%. The allergic rhinitis patients in our department were almost all diagnosed as having persistent allergic rhinitis. A similar pattern of serum specific IgE was identified in nasal polyp and chronic sinusitis patients with a much higher incidence of dust mite than ragweed and pollen. As we discussed in chapter 1, rhinitis, especially nonallergic rhinitis has been suggested to be one of the precursors of sinusitis. Patients with chronic sinusitis and nasal polyps often have a long history of perennial rhinitis. Nonallergic rhinitis with eosinophilia (NARES) is taken as the most important subtype of rhinitis correlated with nasal polyps. In our study, the incidence rates of atopy in nasal polyp and chronic 241 sinusitis were 29.7% and 37.5%, respectively. The incidence rates of atopy in patients with a negative RAST test but with eosinophilia (score≥ 2) in the middle turbinate mucosa were 38% and 25%, in nasal polyp and chronic sinusitis patients, respectively. All if these findings support a closer relationship between nasal polyps/chronic sinusitis and nonallergic rhinitis but not allergic rhinitis. Although serum sIgE level, especially sIgE to Dermatophagoides pteronyssinus and Dermatophagoides farinae of allergic rhinitis patients was significantly higher than that in nasal polyp and chronic sinusitis patients, it is interesting that the eosinophil levels in the middle turbinate mucosa of allergic rhinitis patients were significantly lower than that in nasal polyp tissue/inflamed sinus mucosa. There was no significant difference of eosinophil scores between the middle turbinate mucosa from allergic rhinitis patients and controls. A similar finding was reported by Fokkens et al.99 In their study, there was no significant difference in eosinophil numbers in patients with grass-pollen allergy, compared with nonatopic nasal polyps and normal controls. It has been proposed that the functional heterogeneity rather than the numerical difference of eosinophils should be taken into consideration.100 In addition, the infiltration of eosinophils in nasal polyp tissue and inflamed sinus mucosa may be under the control of chemical mediators released by other inflammatory cells, especially lymphocytes. Langerhans cells were uncommon rare in all our study groups, including nasal polyp, 242 chronic sinusitis and allergic rhinitis patients, and controls. Although the CD1a+ langerhans cell level has been shown to increase in the nasal mucosa of seasonal allergic rhinitis patients,99 a repeated allergen change may mimic the reaction.101 In addition to the important role of langerhans cells in the allergic reaction of nasal mucosa,102 it was proposed that the number of HLA-DR+ cells was much greater than the number of CD1a+ langerhans cells in both the epithelium and lamina propria of the nasal mucosa in allergic patients.99 HLA-DR+ dendritic cells possess a strong stimulatory capacity for resting T lymphocytes but exhibit different properties from the typical epidermal langerhnas cells.103 It was suggested that in nasal mucosa, HLA-DR+ dendritic cells are different from langerhans cells.99 If it is true that in nasal mucosa HLA-DR+ dendritic cell is the more important antigen presenting cell than langerhans cell, we wonder what the exact mechanism might be of antigen presentation in nasal polyps and chronic sinusitis. As reported in previous studies, HLA-DR+ macrophage/dentritic cells clustered in the subepithelium areas with T cells in nasal polyp tissue.104 Therefore, the role of antigen presenting cells in the pathogenesis of nasal polyps and chronic sinusitis needs to be further clarified. Mast cell levels were also not significantly different in our study groups. Studies have reported an increased number of activated mast cells in the epithelium but not in the submucosa of persistent allergic rhinitis patients, as compared to controls.105,106 Whether this phenomenon can be found in our patient population needs to be further clarified. It has to be emphasized that mast cell is proposed to be a residential cell, as 243 well as the major source of IL-4, IL-5 and IL-6 in normal nasal mucosa.107 Even in those patients with numerous IgE-positive mast cells, there was a high percentage showing no clinical evidence in the long-term follow up study.95 It is also widely accepted that in chronic inflammation, eosinophils, basophils and T cells rather than mast cells play a central role. In addition, in our study groups, including allergic rhinitis patients, mast cells are mainly distributed in the lamina propria but not the epithelium. Although mast cell degranulation mainly occurs in the epithelium after allergen challenge, it has been suggested that vigorous allergen exposure may lead to mast cell degranulation in the lamina propria.108 Whether the mast cell degranulation identified in our patients is due to continuous allergen challenge, or non-IgE mediated activation, such as microbial infection, is not known. As has been suggested by Loesel et al.,95 mast cell activation in chronic sinusitis may be caused by both allergens and infectious agents. The contribution of mast cells in chronic inflammation is far from known. Although Th2 cell is taken to play an important role in the pathogenesis of allergic inflammation, our study and some other reports106 did not identify any increased CD4+ T cell levels in persistent allergic rhinitis (PAR) patients. The main feature of allergic rhinitis compared to controls is the inverse ratio of CD4+/CD8+ T cells. This is also identified in nasal polyp and chronic sinusitis patients. However, whether the inverse CD4+/CD8+ T cell ratio in the chronic inflammation in different study groups is caused by a similar or a different mechanism remains an enigma. Although the 244 increased number of CD3+ T cells in PAR has been proven by many studies,105,106 the contribution of CD4+ and CD8+ T cells is unclear. As we discussed in the pathogenesis of nasal polyps and chronic sinusitis, although CD8+ T cells are traditionally taken as the major source of INF-γ, and suppresses the Th2-mediated airway disease, it may play an important role in allergic inflammation in some cases. A study in an animal model has demonstrated that in limited allergen exposure through the airway, CD8+ T cells are essential for the development of eosinophil allergic inflammation and airway hyperreactivity.109 The exact role of CD8+ T cell in the pathogenesis of PAR is in need of further study. One more important point to be addressed is that, in fact, the assessment of the status of atopy by RAST has long been questioned. Many studies suggested that local IgE production rather than serum IgE is more closely correlated with symptoms.110 Patients with local IgE production and symptoms may have negative skin tests.111 On the other hand, patients were reported who have a positive serum RAST test but no local IgE production and no symptoms.112 So far, there are no clear data to evaluate to what extent these factors affect the diagnosis in atopic and nonatopic diseases. Taken together, although allergic rhinitis, especially seasonal allergic rhinitis is well defined, the pathogenesis of PNR may need to be further studied. Continuous allergen challenge and airway remodeling may lead to a mechanism which is different from that in intermittent allergic rhinitis. Inflammatory cell expression and atopy study in 245 nasal polyp and chronic sinusitis patients proves no close relationship with PNR. 2.9 Conclusion Nasal polyp was shown to be a diffuse mucosa disease which involves the middle turbinate mucosa through similar pathogenesic mechanisms. Although chronic sinusitis shows concomitant inflammation in the middle turbinate mucosa as well, the development of inflammation at the two sites may be different. Whether sinusitis is caused by a narrowing or blockage of the normal nasal pathway due to rhinitis and/or nasal polyps or predisposes for the development of rhinitis and/or nasal polyps is not known. The role of allergy and infection in the pathogenesis of nasal polyps and chronic sinusitis has been debated for many years. In our study, we demonstrated that both are characterized by chronic inflammation under the regulation of multiple inflammatory cells, i.e., eosinophils, CD8+ T cells and neutrophils. The lack of eosinophilia with atopic status; rarely seen langerhans cells; and similar level of mast cells compared to controls, called to question the role of IgE-mediated allergy in nasal polyps and chronic sinusitis. However, no evidence of IgE-mediated allergy was found in our patients with persistent allergic rhinitis. This may be due to the cell pattern switch in the late phase reaction; the role of HLA-DR+ dendritic cells rather than langerhans cells in antigen presentation; or non-IgE mediated mast cell activation in normal nasal mucosa. In addition, the diagnosis of atopy may need to be further evaluated. 246 Allergy and infection may have complicated interactions in chronic inflammation. For example, CD8+ T cells are traditionally taken as suppressing Th2 inflammation through the secretion of Th1 cytokines. 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J Immunol 1999; 163(10):5729-5734. 255 [...]... Sinusitis 2. 5.1 Inflammatory Cell Scores in Nasal Polyps and Its Paired Middle Turbinate, and Middle Turbinate of Allergic Rhinitis Patients and Controls 2. 5.1.1 Immunohistochemistry Staining A Nasal Polyps I A B The paired middle turbinate Anti-CD4 (CD4+ T cell) staining of nasal polyps and its paired middle turbinate B II Anti-CD8 (CD8+ T cell) staining of nasal polyps and its paired middle turbinate Figure... between chronic sinusitis patients and allergic rhinitis patients/controls Allergic rhinitis patients had a 151 significantly higher level of sIgE to Dermatophagoides pteronyssinus and Dermatophagoides farinae than chronic sinusitis patients There was no significant difference of serum sIgE between chronic sinusitis patients and controls 2. 5 Inflammatory Cell Scores in Nasal Polyps and Chronic Sinusitis 2. 5.1... combined inflammatory cell infiltration in nasal polyp Nasal polyps are mainly classified into eosinophilic and neutrophilic nasal polyps Eosinophils, neutrophils and mast cells are reported to be the main inflammatory cells in the pathogenesis of nasal polyps However, an indication of the pattern of combined inflammatory cell expression has been lacking In our study, there was no clear pattern in this... changes in the inflamed sinus mucosa of chronic sinusitis patients 2. 4.3 Etiology of Nasal Polyps 2. 4.3.1 Etiology Factors In the nasal polyp group, the ethnic classes were 38 Chinese, two Malays, five Indians, one Philippine, one Nepalese and one British Unilateral and bilateral nasal polyps were shown in 11 and 37 patients, respectively Forty-seven patients had sinusitis (98%), seven unilateral and 40... Eosinophils IV Neutrophils Total 12 15 13 8 48 Total 24 16 5 3 48 3 0 2 3 5 10 3 2 1 0 0 3 2 2 2 5 2 11 2 0 0 3 0 3 1 4 10 4 0 18 1 1 9 1 2 13 0 6 1 1 1 9 0 21 6 1 1 29 NP (MT) 0 1 2 3 Total 0 1 2 3 Total NP (MT) NP NP V Mast cells VI B cells Total 24 17 0 7 48 3 0 0 0 1 1 2 0 2 0 3 5 1 2 11 0 1 14 0 22 4 0 2 28 0 1 2 3 Total NP (MT) NP VII Langerhans cells 164 Table 17 Distribution and correlation of. .. groups (between nasal polyp /sinusitis patients with and without atopy; between nasal polyp /sinusitis patients with and without asthma; between nasal polyp /sinusitis patients and controls), Wilcoxon rank sum test for 2- independent samples was applied V In the subgroup of patients having nasal polyps and chronic sinusitis with available nasal polyp tissue, sinus mucosa as well as middle turbinate mucosa... remodeling is commonly found in nasal polyps and allergic rhinitis patients, including hyperplasia of epithelial cells, basement membrane thickening and inflammatory cell infiltration All cell types were mainly found in the lamina propria except langerhans cells which were mainly seen in 154 the epithelium Infiltration of eosinophils and CD8+ and CD4+ T cells could also be found in the epithelium CD8+ and. .. between nasal polyp and its paired middle turbinate (Table 17) Total 13 5 14 16 48 Total 7 12 6 23 48 3 0 1 1 8 10 3 0 3 2 15 20 2 0 0 9 5 13 2 1 2 1 4 8 1 6 3 2 1 14 1 4 6 2 2 14 0 7 1 2 2 12 0 2 1 1 2 6 0 1 2 3 Total 0 1 2 3 Total 1 NP (MT) NP 2 NP (MT) NP I CD4+ T cells II CD8+ T cells Table 16 (I to VII) Cell score distribution in the paired samples from nasal polyp patients (nasal polyp tissue and. .. of nasal polyp and its paired middle turbinate A B IV Anti-neutrophil elastase (neutrophil) staining of nasal polyp and its paired middle turbinate A B V Anti-tryptase (mast cell) staining of nasal polyp and its paired middle turbinate 153 Figure 9, Continued A Nasal Polyps B The paired middle turbinate VI Anti-CD1a (langerhans cell) staining of nasal polyp and its paired middle turbinate A B VII Anti-CD19... staining of middle turbinate mucosa from allergic rhinitis patients and controls B Anti-CD8 (CD8+ T cell) staining of middle turbinate mucosa from allergic rhinitis patients and controls Figure 10 (I to VII) Immunohistochemistry staining of CD4+ and CD8+ T cells, eosinophils, neutrophils, mast cells, CD19+ B cells and CD1a+ langerhans cells in middle turbinate of allergic rhinitis patients (A) and . inflammation and in inducing nasal airway remodeling. IV. There may be ethnic based differences controlling cell patterns involved in the chronic inflammation of nasal polyps and chronic sinusitis. . difference of serum sIgE between chronic sinusitis patients and controls. 2. 5 Inflammatory Cell Scores in Nasal Polyps and Chronic Sinusitis 2. 5.1 Inflammatory Cell Scores in Nasal Polyps and Its. patients. 2. 2 Aim of Study 2. 2.1 Hypothesis The underlying mechanism of chronic sinusitis and nasal polyps involves a complex inflammation characterized by infiltration and activation of various