Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS-CoV-2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS-CoV-2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP. METHODS: The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. RESULTS: ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN-γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN-γ up-regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co-expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. CONCLUSION: These findings indicate that ACE2 expression, regulated by IFN-γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.

Lactate dehydrogenase as a marker of nasopharyngeal inflammatory injury during viral upper respiratory infection: implications for acute otitis media.

BACKGROUND: Acute otitis media (AOM) is a frequent complication of viral upper respiratory tract infection (URI). We hypothesized that the severity of nasopharyngeal cellular injury during URI, as measured by lactate dehydrogenase (LDH) concentrations in nasopharyngeal secretions (NPSs), is related to AOM complication. METHODS: LDH concentrations were determined in NPS samples (n = 594) that were collected at the initial visit for URI from 183 children who were followed for the development of AOM. A subset of NPS samples (n = 134) was analyzed for interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α concentrations. RESULTS: AOM complication was independently predicted by LDH concentrations (median mU/ml with AOM = 2,438 vs. without AOM = 1,573; estimate = 0.276; P = 0.02). LDH effect on AOM development was highest during the first 4 d of URI. LDH concentrations were higher in URIs due to adenoviruses, bocaviruses, and rhinoviruses as compared with virus-negative samples (P < 0.05). There was a positive correlation between concentrations of LDH and all cytokines (P < 0.001). CONCLUSION: LDH concentrations in NPS are positively associated with AOM risk, suggesting that the severity of nasopharyngeal inflammatory injury during URI contributes to the development of AOM and that reduction of inflammatory injury may reduce the risk for AOM.

[Role of the -765 G/C polymorphism of COX-2 gene in pathogenesis of chronic rhinosinusitis with nose polyps in a Polish population]. / Znaczenie polimorfizmu -765G/C genu COX-2 dla patogenezy przewleklego zapalenia zatok przynosowych z polipami nosa w populacji polskiej.

INTRODUCTION: It is believed that local factors within the nasal cavities contribute to the formation of nasal polyps. The disruption of local homeostasis mechanisms in a chronic inflammatory process is one of those factors. Cyclooxygenase (COX)-2 expression is activated in the course of the immune response to extracellular and intracellular stimuli. Also, an increase of the gene expression can be associated with the development of nasal polyps in patients with chronic sinusitis. THE AIM OF THE STUDY: The aim of this study was an evaluation of the role of the -765G/C COX-2 polymorphism in sinusitis pathogenesis in patients with nasal polyps. MATERIALS AND METHODS: The study group consisted of 100 patients, aged 35-65, with chronic sinusitis and nasal polyps and 150 people in the age, sex-, age- and ethnicity-matched control group. The study material included DNA isolated from peripheral blood lymphocytes of the patients and the controls. PCR-RFLP method was used in genotyping polymorphic variants of COX-2. RESULTS: In comparison to the control group, the group of the patients with chronic sinusitis and nasal polyps showed a statistically significant increase in the occurrence frequency of the -765G/C polymorphic variant of COX-2 gene (OR 4.04; 95% CI 2.32-7.03; p > 0.001) and C allele (OR 3.68; 95% CI 2.38-5.68; p < 0.001). CONCLUSIONS: The -765G/C genotype of COX-2 can be associated with an increased risk of the occurrence of chronic sinusitis with nasal polyps in the Polish population.

Differential expression of angiotensin-converting enzyme-2 in human paranasal sinus mucosa in patients with chronic rhinosinusitis.

OBJECTIVE: Severe acute respiratory syndrome coronavirus-2 uses angiotensin-converting enzyme-2 as a primary receptor for invasion. This study investigated angiotensin-converting enzyme-2 expression in the sinonasal mucosa of patients with chronic rhinosinusitis, as this could be linked to a susceptibility to severe acute respiratory syndrome coronavirus-2 infection. METHODS: Ethmoid sinus specimens were obtained from 27 patients with eosinophilic chronic rhinosinusitis, 18 with non-eosinophilic chronic rhinosinusitis and 18 controls. The angiotensin-converting enzyme-2 and other inflammatory cytokine and chemokine messenger RNA levels were assessed by quantitative reverse transcription polymerase chain reaction. Angiotensin-converting enzyme-2 positive cells were examined immunohistologically. RESULTS: The eosinophilic chronic rhinosinusitis patients showed a significant decrease in angiotensin-converting enzyme-2 messenger RNA expression. In the chronic rhinosinusitis patients, angiotensin-converting enzyme-2 messenger RNA levels were positively correlated with tumour necrosis factor-α and interleukin-1ß (r = 0.4971 and r = 0.3082, respectively), and negatively correlated with eotaxin-3 (r = -0.2938). Angiotensin-converting enzyme-2 immunoreactivity was mainly localised in the ciliated epithelial cells. CONCLUSION: Eosinophilic chronic rhinosinusitis patients with type 2 inflammation showed decreased angiotensin-converting enzyme-2 expression in their sinus mucosa. Angiotensin-converting enzyme-2 regulation was positively related to pro-inflammatory cytokines, especially tumour necrosis factor-α production, in chronic rhinosinusitis patients.

Variability of the L-Histidine decarboxylase gene in allergic rhinitis.

BACKGROUND: Nonsynonymous polymorphisms in genes coding for histamine-metabolizing enzymes, diamine oxidase and histamine N-methyltransferase are related to the risk of developing allergic diseases. The role of polymorphisms in the histidine decarboxylase gene remains unexplored. The objective of this study is to identify novel polymorphisms in the human histidine decarboxylase gene and to analyse the clinical association of nonsynonymous polymorphisms with rhinitis. METHODS: We performed a single-strand conformational polymorphism analysis of the histidine decarboxylase gene sequence. The presence of two nonsynonymous polymorphisms Thr31Met (rs17740607) and Glu644Asp (rs2073440) was analysed in 442 unrelated patients with allergic rhinitis, 233 of whom also had asthma, and in 486 healthy subjects. RESULTS: We observed three novel polymorphisms designated as ss50402829, ss50402830 and ss50402831-(rs17740607) with allele frequencies = 0.005, 0.208 and 0.073, respectively. Statistically significant differences were observed for the histidine decarboxylase Glu644Asp (rs2073440) polymorphism, with OR (95% CI) values for homozygous carriers of the Glu644 allele equal to 3.12 (1.75-5.56, P < 0.00005) for all patients, 3.38 (1.54-7.44, P = 0.002) for patients with rhinitis alone, and 2.92 (1.43-5.95), P = 0.003 for patients with rhinitis + asthma, when compared with healthy controls. A significant Glu644 gene-dose effect was observed for overall patients (P = 0.0001), for patients with rhinitis alone (P = 0.005) and for patients with rhinitis + asthma (P = 0.010). CONCLUSIONS: The HDC allele Glu644 in homozygosity increases the risk of developing rhinitis in the studied population. This adds to increasing evidence supporting a prominent role of genetic variations related to histamine homeostasis in the risk to develop allergic diseases.

[Cathepsin D activity in chronic rhinosinusitis with nasal polyps]. / Ocena aktywnosci katepsyny D w blonie sluzowej pacjentów z przewleklym zapaleniem zatok przynosowych z polipami.

UNLABELLED: Nasal polyposis affects about 1 to 4% of the population. Polyps develop in oedematous and inflammated mucous membrane. In spite of the intensive research the pathomechanism of their development is not fully understood. The majority of the theories concerning the development of nasal polyps emphasize the role of the inflammatory process causing the rupture of the epithelium and the basal membrane. Cathepsin D is one of important mediators of inflammatory processes, that may be involved in the pathogenesis of nasal polyposis. THE AIM OF THE STUDY: was to establish the role of the cathepsin D in the pathogenesis of nasal polyps. MATHERIAL AND METHOD: Tissues were taken from 39 patients treated with endoscopic sinus surgery due to chronic rhinosinusitis with polyps. The activity of the cathepsin D was assesed with spectrofotometric method using the specific inhibitor (pepstatin) in tissue of nasal polyps, in oedematous and the inflammated mucous membrane of the nasal conchae and the samples of mucous membrane taken from the nasal septum. RESULTS: Statistically significant difference in cathepsin D activity between polypoid tissue, inflammated mucosa and the mucous membrane of the nasal septum was detected (t-student test, p < 0.05). No difference in the activity of this enzyme was observed between the polypoid tissue and the inflammated mucosa. CONCLUSION: Increased activity of the cathepsin D in nasal polyps and inflammatory changed mucosa confirm the important role of the cathepsin D in inflammatory processes leading to damage and subsequent remodeling of mucous membrane. We believe that further research on the activity of other proteolytic enzymes is necessary to demonstrate the differences between the inflammable changed mucous membrane and nasal polyps.

[The role of infection in the development of polypous rhinosinusitis in patients with bronchial asthma].

At present, many authors accept the many-factor theory of development of polypous rhinosinusitis associated with bronchial asthma according to which this condition should be regarded as an inflammatory syndrome in subjects predisposed to a specific tissue reaction. Inflammation induced by an infection is accompanied by the release of protease-inhibiting enzymes that turn inflammation into a chronic process thereby contributing to tissue disintegration, remodeling of mucous membranes, and development of polyps.

[Study on the relationship between 11ß-hydroxysteroid dehydrogenase and glucocorticoid response in nasal polyps].

Objective: To investigate the expression of 11ß-hydroxysteroid dehydrogenase (11ß-HSD) in polyps of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and its correlation with glucocorticoid sensitivity. Methods: The prospective study method was applied. Forty-three adult CRSwNP patients from Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University between April 2016 and June 2017 were enrolled in this study. There were 19 males and 24 females with the age of (37.44±7.42) years old. The endoscopic scores by nasal Polyps Grading System before and after one-week prednisone treatment (0.5 mg/(kg·d)) were evaluated. The response of glucocorticoid by the total endoscopic scores was estimated. According to the patient's reduced nasal polyp endoscopic score, patients were devided into nasal polyps insensitive to glucocorticoids treatment group (insensitive group) and nasal polyp sensitive to glucocorticoids treatment group (sensitive group). The expression of 11ß-HSD1, 11ß-HSD2 in nasal polyps were measured by Real-time PCR (RT-PCR), Western Blot and immunohistochemisty. According to the clinical data, the Logistic regression models and receiver operation characteristics (ROC) curves were used to explore the predictor for glucocorticoid response in CRSwNP. Results: The expression of 11ß-HSD1 and 11ß-HSD1/11ß-HSD2 was higher in sensitive group than that of insensitive group, while the expression of 11ß-HSD2 was lower (rank average was 26.08 vs 16.33, 27.24 vs 14.72, 18.66 vs 26.64, Z value was -2.511, 0.323, -2.059, respectively, all P<0.05). The endoscopic scores in CRSwNP group declined whereas the expression of 11ß-HSD1/11ß-HSD2 increased (r=0.528, P=0.001), while the cutoff value of the ratio of 11ß-HSD1/11ß-HSD2 was 2.290 (sensitivity was 79.17%, specificity was 88.89%). Conclusions: There is a positive correlation between the response of glucocorticoid and the ratio of 11ß-HSD1/11ß-HSD2, which could be used as a marker in predicting the level of tissue response to glucocorticoid therapy in CRSwNP.

Increased nasal matrix metalloproteinase-1 and -9 expression in smokers with chronic rhinosinusitis and asthma.

A potential mechanism underlying cigarette smoke-induced airway disease is insufficient tissue repair via altered production of matrix metalloproteinases (MMPs). Osteitis is a signature feature of recalcitrant chronic rhinosinusitis (CRS) and often results in revision surgery. The present study aimed to investigate MMP expression in the nasal tissues of asthmatic patients with CRS and any association with cigarette smoking and osteitis. Thirteen smokers with CRS and asthma, 16 non-smokers with CRS and asthma, and seven non-smoker asthmatic patients without CRS were prospectively recruited. The expression of MMPs and associated immunological factors in surgically-obtained nasal tissues was evaluated via real-time PCR and western blotting. Maximal bone thickness of the anterior ethmoid (AE) partition was measured in axial sinus computed tomography (CT) sections. MMP-1 and MMP-9 expression was increased in the nasal tissues of smokers with asthma and CRS via real-time PCR and western blot. Maximal AE partition bone thickness was greater in smokers with CRS and asthma than in non-smokers with CRS and asthma. MMP-1 and MMP-9 levels were correlated with maximal AE bone thickness. Cigarette smoking was associated with the up-regulation of MMP-1 and MMP-9 in the nasal tissues of patients with airway inflammatory diseases, and with AE osteitis, and with therapeutic resistence.

Emerging Role of Proteases in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous upper airway disease with multiple etiologies. Clinically, CRSwNP can be classified into either eosinophilic or non-eosinophilic subtypes. The eosinophilic phenotype of CRSwNP is widely thought to be highly associated with recurrence of nasal polyps or surgical failure. Epithelial cells have a crucial role in the development of Th2-biased airway diseases. Recent studies have shown that a wide range of external stimuli such as allergens and microorganisms can elicit the release of epithelial-derived Th2-driving cytokines and chemokines. Protease activity is a feature common to these multiple environmental insults and there is growing evidence for the concept that an imbalance of proteases and protease inhibitors in the epithelial barrier leads to both the initiation and maintenance of chronic eosinophilic airway inflammation. In this review, we analyze recent work on the role of proteases in the development of the sinonasal mucosal type 2 immune response with an emphasis on the molecular pathways promoting adaptive Th2 cell immunity.

Involvement of cyclooxygenase-2 in allergic nasal inflammation in rats.

This study was undertaken to investigate the involvement of cyclooxygenase-2 (COX-2) in allergic nasal inflammation in actively sensitized rats. An allergic rhinitis model was developed by the repeated topical application of antigen into the nasal cavities in the sensitized rats. The severity of allergic rhinitis was studied by measuring the nasal behavior, as well as electroencephalogram (EEG) activity by antigen challenge. The electrodes were implanted chronically into the bilateral olfactory bulb of the rats and the EEG was measured monopolarly with an electroencephalograph (EEG, Nohon Kohden, Japan). The intranasal application of antigen caused the increase of nasal allergic signs as well as an EEG spike in a dose-dependent fashion, and at a dose of 50 microg/site, it showed a significant effect. The responses induced by the antigen were evaluated with certain drugs, etodolac (a selective COX-2 inhibitor), indomethacin (a non-selective COX inhibitor), ramatroban (a thromboxane A2 receptor antagonist) and zafirlukast (a cys-leukotriene receptor antagonist). Etodolac showed the inhibition of nasal behavior and EEG spike in a dose-related fashion, and at doses of 3 and 10 mg/kg, it showed a significant effect. Moreover, ramatroban also caused the dose-related inhibition of nasal behavior and EEG spike induced by antigen. On the other hand, both indomethacin and zafirlukast had no effects on the responses induced by antigen, even at a higher dose. Therefore, it can be concluded that cyclooxygenase-2 actively participates in the allergic nasal inflammation in actively sensitized rats.

Expression of cyclooxygenase and lipoxygenase enzymes in nasal polyps of aspirin-sensitive and aspirin-tolerant patients.

OBJECTIVE: To evaluate the expression of cyclooxygenase (COX) and lipoxygenase (LO) enzymes in nasal polyp specimens from aspirin-sensitive (AS) and aspirin-tolerant (AT) patients. DESIGN: Immunohistochemical staining of archived tissue. Subjects Specimens from 26 patients (11 AS and 15 AT) with nasal polyps were analyzed; specimens from 4 patients were used as controls. INTERVENTIONS: Immunohistochemical techniques were used to evaluate the expression of the enzymes COX-1, COX-2, 5-LO, 12-LO, and 15-LO in nasal polyp tissue specimens from AS and AT patients. The results were compared with those of a control group of patients without a history of nasal polyposis or rhinosinusitis. RESULTS: Characteristic staining patterns of epithelium and submucosal glands were noted for each enzyme. Statistically significant (P<.05) differences in staining of columnar epithelium were noted for COX-1 (basal cell layer cytoplasm), COX-2 (apical cell layer cytoplasm), and 12-LO (full-thickness cytoplasm and nucleus). Increased 15-LO (full-thickness cytoplasm) expression in columnar epithelium was noted only in the AT group. Significant differences in the staining of submucosal glands were noted for COX-2 (plasma membrane and cytoplasm), 12-LO (cytoplasm), and 15-LO (cytoplasm) between control and AS patients as well as between control and AT patients (P<.05). The only significant difference noted between the AS and AT groups was cytoplasm staining for 5-LO in submucosal glands, which was greater in the AS group. No epithelial staining differences were noted between AT and AS patients. CONCLUSIONS: There were significant differences in the expression of COX and LO enzymes between patients with nasal polyps and controls, irrespective of aspirin sensitivity. With 1 exception, there were no significant differences between AS and AT groups.

Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders.

Lens epithelium-derived growth factor p75 (LEDGF/p75) is a nuclear autoantigen in atopic disorders implicated in cellular protection against stress-induced apoptosis. We observed that LEDGF/p75 was cleaved during apoptosis into fragments of 65 and 58 kD generated by caspases-3 and -7 cleaving at three sites: DEVPD30/G, DAQD486/G and WEID85/N. Sequence analysis revealed that the DEVPD30/G and WEID85/N sites lie within the highly conserved HATH (homologous to amino terminus of hepatoma-derived growth factor) region, also known as PWWP domain. Alignment of proteins containing this domain failed to reveal conservation of the DEVPD30/G and WEID85/N sites, suggesting that the HATH/PWWP domain of LEDGF/p75 may be specifically targeted by caspases. Overexpression of LEDGF/p75 protected HepG2 cells from serum starvation-induced cell death, whereas expression of the 65 kD fragment failed to protect. The apoptotic cleavage of LEDGF/p75 may contribute to the pathogenesis of atopic disorders by abrogating its pro-survival function and enhancing its immunogenicity.

Loss of dipeptidylpeptidase IV activity in chronic rhinosinusitis contributes to the neurogenic inflammation induced by substance P in the nasal mucosa.

In this study, we have found that dipeptidylpeptidase IV (DPPIV) plays in vivo an active role in the modulation of the inflammatory response of chronic rhinosinusitis. Human nasal mucosa expresses DPPIV-like immunoreactivity in submucosal seromucus glands, leukocytes, and endothelial cells of blood vessels. DPPIV enzymatic activity in nasal tissue biopsies taken from patients suffering from chronic rhinosinusitis was correlated inversely with the density of inflammatory cells in the nasal mucosa, and the DPPIV activity rose when chronic rhinosinusitis was treated. By using a pig animal model, we have shown that the intranasal administration of recombinant DPPIV decreased the vasodilatation induced by exogenous substance P (SP), a proinflammatory peptide released by sensory nerves. In contrast, an inhibitor of DPPIV enhanced the vasodilatatory effect at low doses of SP. SP5-11 was 100- to 1000-fold less potent than SP as a vasodilator of the nasal mucosa. The vasodilatatory effect of SP was abolished by a NK1 receptor antagonist. In conclusion, these results suggest a new pathophysiological pathway for rhinitis based on clinical observations in humans, indicating the involvement of an enzyme to modulate non-adrenergic and non-cholinergic substrate that occurred during nasal dysfunctions.

Local and systemic proteolytic responses in chronic rhinosinusitis with nasal polyposis and asthma.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma coexist frequently and share similar features of inflammation and remodeling. Remodeling has become an important concept in the pathophysiology of asthma and CRSwNP. It happens early in the development of these diseases and is relatively resistant to treatments. The key enzymes responsible for remodeling are matrix metalloproteinases (MMPs). In this study we examined whether asthma and CRSwNP share similar MMP profiles. METHODS: Nasal secretion and serum specimens of controls (19 subjects) and patients with asthma (12), CRSwNP (39), or both (16) were collected between December 2007 and May 2009. Groups were divided into 2 subgroups according to atopy. MMP-7, MMP-9, MMP-13, tissue inhibitors of metalloproteinases (TIMPs), TIMP-1 and TIMP-2, myeloperoxidase (MPO), and human neutrophil elastase (HNE) were measured using enzyme-linked immunosorbent assay (ELISA), and MMP-8 was determined using immunofluorometric assay. High-sensitivity C-reactive protein (hs-CRP) was measured to estimate systemic involvement. RESULTS: Patients with asthma, CRSwNP, or both exhibited lower MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and MPO in nasal secretions (p < 0.05 in CRSwNP) and higher MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and HNE in serum (p < 0.05 in all groups) compared to controls, whereas no difference in MMP-7, MMP-13, TIMP-1, and TIMP-2 were detected. Atopy increased nasal MMP-9 and MPO expression. hs-CRP was higher in patients with CRSwNP and asthma compared to controls. CONCLUSION: Our findings suggest shared pathomechanisms behind asthma and CRSwNP. Contrasting local vs systemic results reflect a different ability of healthy mucosa to react to exogenous stimuli, possibly indicating a protective function of MMP-9 and possibly also MMP-8 in the airways.

Chronic non-allergic hypertrophic rhinitis. A histochemical study.

The enzymatic changes in chronic hypertrophic rhinitis were studied in 14 patients. The cholinesterase content was increased in the subepithelium and stroma, denoting parasympathetic hyperactivity. Acid phosphatase was increased in the epithelium, subepithelium and around the glands, indicating increased shedding and phagocytic activity. Succinic dehydrogenase, alkaline phosphatase and alpha-esterase were increased in the mucous glands, denoting increase secretory activity, hence increased natural defence mechanism of the nasal mucosa.

The enzymology of nasal secretion.

Normal human nasal fluid contains several enzymes of the intermediary metabolism as well as a specific protease inhibitor, which inhibits trypsinm chymotrypsin and leucocytic proteases. During the course of acute and chronic nasal and paransal sinus infections the inhibitor level varies. The inhibitor level is an indicator of poor healing. It is possible too, to differentiate viral rhinitis from bacterial or allergic or atrophic rhinitis by a signigicant increase of the activities of the enzymes GOT, LDH and CPK.

Submucous diathermy of the inferior turbinates in chronic hypertrophic rhinitis.

Twenty patients, 10 allergic and 10 non-allergic, with chronic hypertrophic rhinitis and presenting mainly with bilateral nasal obstruction were subjected to submucosal diathermy of their inferior turbinates. There was significant post-operative improvement clinically, histopathologically and histochemically in the non-allergic group, while the improvement was less obvious in the allergic cases. The post-operative clinical improvement as regards rhinorrhea and sneezing was not as marked as that for nasal obstruction. Evaluation of the results showed that submucous diathermy of inferior turbinates is a good line of treatment for cases of chronic hypertrophic rhinitis, with better results in the non-allergic group of patients.

[Clinical and morphofunctional changes in the mucosa of the inferior nasal conchae in various forms of chronic rhinitis]. / Klinicheskie i morfofunktsional'nye izmeneniia slizistoi obolochki nizhnikh nosovykh rakovin pri nekotorykh formakh khronicheskogo rinita.

Having in view the concept about a close relationship between morphofunctional changes and clinical picture of the disease, 35 patients of different sex, age and various duration of the disease were examined, in order to clarify certain modifications of chronic rhinitis and mechanisms of its pathogenesis. It was found that the forms of the disease were characterized by structural changes of the mucosa, whose microrhinoscopic picture was very different in the case of hyperplastic rhinitis. Changes in hydrolytic enzymes were dissimilar in the case of various clinical forms of the disease. Most demonstrative were the changes in alkaline phosphatase and ATPase in the glandular epithelium and walls of blood vessels in the mucosa. This can be used as an indirect sign of the functional state of the mucosa. Significant enzymatic changes reflect metabolic shifts in mucous structural components and can serve as the basis for the development of hypertrophic and hyperplastic processes.

Relationships of indoleamine 2,3-dioxygenase activity and cofactors with asthma and nasal polyps.

BACKGROUND: Asthma and chronic rhinosinusitis with nasal polyps (CRSwNPs) are coexisting diseases that are multifactorial. The rural environment seems to protect from atopy, but its relation with nonatopic airway inflammations has been less investigated. Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in the catabolism of the essential amino acid tryptophan (Trp) to kynurenine (Kyn). Low IDO activity has been previously observed in atopy and asthma. The objective was to investigate the relationships of IDO activity, eosinophils, and cofactors during asthma and/or CRSwNPs. METHODS: A Finnish population-based cohort of adult asthmatic patients (n = 245) and nonasthmatic patients (n = 405) was used. The presence of asthma and atopy were based on patient history and standardized diagnostic tests. The presence of acetyl salicylic acid intolerance, doctor-diagnosed NPs, and countryside environment during childhood were based on a questionnaire report. Serum IDO activity was evaluated by assessing the Kyn/Trp ratio by liquid chromatography. RESULTS: Low IDO activity was associated significantly with atopy, CRSwNPs, and an urban background. IDO activity did not correlate with pulmonary function. As expected, CRSwNPs was more frequent among asthmatic patients. A rural background has a protective effect from atopy and atopic asthma but it did not affect the prevalence of CRSwNPs or nonatopic asthma. CONCLUSION: Low IDO activity might result from the urban environment and influence the development of the atopic phenotype. On the other hand, low IDO activity, found in CRSwNPs, does not seem to be related to the urban background and thus may result from other, still unknown, factors.