[Inclusion of vaccination into clinical pathways for COPD and asthma: current challenges and future perspectives in Italy]. / La vaccinazione dei pazienti con BPCO e Asma nei PDTA in Italia: gap da colmare e prospettive future.

OBJECTIVES: to describe the importance given to vaccination as a preventive measure in the clinical pathways (CPWs) of patients affected by chronic obstructive pulmonary disease (COPD) and asthma in the Italian regional healthcare services. DESIGN: a comparative analysis was conducted to assess the presence/absence of vaccination recommendations among the available regional CPWs for the management of COPD and asthma. SETTING AND PARTICIPANTS: all the regional CPWs for COPD and asthma available in the "Fondazione ReS" database between 2008 and 2019 have been analysed. MAIN OUTCOME MEASURES: the role attributed to vaccination was assessed in terms of type of recommended vaccinations, management step indicated for administration, vaccination schedules, healthcare professionals involved in the vaccination pathway, potential contraindications, use of indicators for the monitoring of the offer. RESULTS: thirteen CPWs for COPD and only 3 for asthma were published between 2008 and 2019. Twelve of the CPWs for COPD included recommendation for influenza vaccination, 11 of which including also pneumococcal vaccination. The most recent CPW also contained recommendations for measles-mumps-rubella, varicella, Herpes Zoster, and tetanus-diphtheria-acellular pertussis vaccinations. Two of the CPWs related to asthma in adults recommended influenza vaccination. All CPWs provided for the vaccination recommendations during the patient follow-up step. CONCLUSIONS: Italian CPWs still pay little attention to the topic of vaccinations in patients with COPD and asthma. CPWs are required to be updated in the future being compliant with the national immunization schedule recommendations.

Baseline Inappropriate Antibiotic Use in Primary Care Patients with Viral Respiratory Tract Infections with 2019 and 2020.

Context: Respiratory tract infection (RTI) is the leading cause of avoidable antimicrobial use in primary care. How the COVID-19 pandemic has impacted antibiotic prescribing practices across Canada is unknown. The purpose of this study was to examine rates of antibiotic prescribing for RTI in primary care during the first year of the pandemic (2020), compared to baseline in 2019. Study Design and Analysis: Cross sectional study. Dataset: Canadian Primary Care Sentinel Surveillance Network electronic medical record data from sites in British Columbia, Alberta, Manitoba, Ontario, Quebec, Nova Scotia and Newfoundland. Population Studied: Patients that met the case definition criteria for an RTI or a Urinary Tract Infection (UTI) in 2019, and in 2020. Outcome measures: We examined oral antibiotic prescribing for patients who were identified as having a primary care visit for RTI. The same analysis was repeated for urinary tract infection (UTI) as a tracer condition. The antibiotic use considered avoidable for RTI was defined by Choosing Wisely Canada. Results: A total of 1,692,876 patients with a valid birth year and sex and at least one visit to primary care in 2019 and 2020 were included. Patient visits for RTI decreased from 2.3% in 2019 to 1.6% in 2020 (p<.0001), as did patient visits for UTI (1.1% vs 0.7%, p<.0001). In 2019, 28.0% of patients visits for RTI were prescribed an antibiotic, and this proportion decreased significantly to 20.6% in 2020 (<.0001). The drop in antibiotic prescriptions for RTI was driven by a decrease in prescribing for common cold (13.6% vs. 11.3%, <.0001) and for acute bronchitis/asthma (15.2% vs. 7.3%, p<.0001). In comparison, antibiotic prescribing for visits related to UTI increased marginally between 2019 and 2020 (71.6% vs. 72.3%, p=0.007). Conclusions: A significant decrease in antibiotic prescribing for RTI across primary care was observed during the first year of the COVID-19 pandemic, likely related to the changes in epidemiology and care delivery models in primary care. CPCSSN can provide pan-Canadian surveillance of antibiotic prescribing practices in primary care that can be used for provider feedback and quality improvement.

Application of Nursing Intervention Based on Nel Noddings Care Theory for School-Aged Asthmatic Children.

Objectives: The objective of this study was to examine the effect of nursing intervention based on Nel Noddings care theory on self-management behavior and symptomatic improvement in school-age asthmatic children in China. Methods: In this study, a sample of 100 school-aged children suffering from asthma was chosen, and divided into two groups: observation group and control group. Both groups received routine nursing but the observation group was combined with nursing intervention based on Nel Noddings theory.Results:The total scores of social psychologies, daily life, disease medicine and self-management in the observation group before intervention were similar to those in the control group. The self-management scores of the observation group after intervention were higher than those of the control group. The improvement time of wheezing and cough in the observation group was shorter than that in the control group. The total number of complete compliance and partial compliance in the observation group was higher than that in the control group. Conclusion: The application of nursing intervention based on Nel Noddings care theory to the nursing of school-age asthmatic children can improve the self-management ability of children, promote the recovery of cough, wheezing and other symptoms, and is of great significance to improve the compliance and nursing effect of children, with high popularization and application value.

Determination of the effects of advanced glycation end products receptor polymorphisms and its activation on structural cell responses and inflammation in asthma.

BACKGROUND: Advanced glycation end products receptor (RAGE) is a pattern recognition receptor which attracted attention in chronic airway diseases recently. This study aimed to determine the association of RAGE with asthma and the cellular responses resulting from RAGE signaling pathway activation. METHODS: Asthmatic (n = 362) and healthy (n = 134) children were genotyped by PCR-RFLP. Plasma sRAGE levels were determined by ELISA. Lung structural cells were stimulated with AGEs (advanced glycation end products) and control BSA. Expressions of cytokines and protein levels were determined by real-time PCR and ELISA. RESULTS: : Gly82Ser and -374 T/A polymorphisms in RAGE gene were associated with lower plasma sRAGE levels (p < 0.001 and p < 0.025, respectively). AGE stimulation increased the expression of RAGE (p = 0.002), ICAM-1 (p = 0.010) and VCAM-1 (p = 0.002) in endothelial cells; TIMP-1 (p = 0.003) and MCP-1 (p = 0.005) in fibroblasts. AGE stimulation increased protein levels of IL-6 (p < 0.001) in endothelial cells; VEGF (p = 0.025) and IL-8 (p < 0.001) in fibroblasts; IL-1b (p < 0.001) and VEGF (p = 0.007) in epithelial cells. DISCUSSION: Activation of RAGE pathway may contribute to asthma pathogenesis by increasing the expression of several asthmarelated genes. These findings suggest that suppression of RAGE signaling may be an alternative candidate for treating asthma.

Characteristics of children with cat sensitivity: a prospective cross-sectional study.

BACKGROUND: Animal dander is one of the most common respiratory allergens in children, and there is evidence that cat sensitivity is a risk factor for asthma and allergic rhinitis. In this study, it was aimed to evaluate children with cat sensitivity and to identify their demographic and clinical characteristics. METHODS: Patients who were found to be sensitive to cats following skin prick tests performed in our allergy clinic over a period of one year (and two control groups), were included in the study. Patients in the study and control groups filled in a questionnaire including demographic and clinical characteristics. RESULTS: The prevalence of cat sensitivity in our allergy clinic was 6% (182/3033). The most common diagnoses in patients were 41.8% allergic rhinitis, 25.8% asthma, and 13.2% allergic rhinitis + asthma. Allergic rhinitis symptoms were the most prevalent symptom associated with cat contact (29.4%), whereas 28% of the patients were asymptomatic. Only 17.3% had a cat at home and 13.4% had cat exposure apart from home but having a cat at home was significantly higher than the control groups (p < 0.05). Eosinophilia was present in 54.6% of the patients, and 17.3% had blood tIgE levels of >1000 IU/mL. Eosinophilia and tIgE levels were significantly higher than both control groups (p < 0.05). DISCUSSION: Cat ownership can affect the development of cat sensitivity but the majority of patients with cat sensitivity are not cat owners. Elevated tIgE levels (> 1000 IU/mL) may be associated with cat sensitivity, these patients should be evaluated for cat sensitivity, even if they do not report symptoms with cat contact.

[The increased expression of stromal cell-derived factor-1 (SDF-1) alleviates airway inflammation in asthmatic rats by promoting the migration of bone marrow mesenchymal stem cells (BMSCs)].

Objective To observe the correlation of stromal cell-derived factor 1 (SDF-1) with bone marrow mesenchymal stem cell (BMSCs) migration and airway inflammation in asthmatic rats. Methods Twenty-four clean SD rats were randomly divided into normal control (NC) group, model control (MC) group, and BMSCs group. Asthma model was established by OVA. In the BMSCs group, 1×106 BMSCs (1 mL) were transplanted into the tail vein on the day the model was completed. Pathological changes in lung tissues were evaluated by HE staining. The count of inflammatory cells in bronchoalveolar lavage fluid(BALF) was evaluated by Wright-Giemsa staining. The concentrations of IL-4, IL-5, IL-13, IgE, IgG1 and IgG2a in BALF were tested by ELISA. The expression of SDF-1 and STAT6 mRNA in lung tissue was measured by real time quantitative PCR. The expression of SDF-1 protein in bronchial epithelial cells were evaluated by Immunofluorescence staining. The expression of SDF-1 and STAT6 protein in lung tissue were measured by Western blot analysis. Results Compared with the normal group, the number of relative inflammatory cell counts and the concentrations of IL-4, IL-5, IL-13, IgE, IgG1, and IgG2a in BALF of the MC group increased significantly. The mRNA and protein expression of SDF-1 and STAT6 in lung tissue increased significantly. Compared with the MC group, inflammatory cells and inflammatory cytokines of BALF of BMSCs group were decreased in numbers, as was the expression of SDF-1 and STAT6 in lung tissues. Compared with the MC group, the expression of SDF-1 gene in lung tissues was increased, as was the expression of SDF-1 protein in bronchial epithelial cells. Conclusion In the process of asthmatic inflammation, the expression of chemokine SDF-1 in the damaged site increases, and promotes the migration of exogenous BMSCs to the lung tissue of asthmatic rats. BMSCs can regulate immune imbalance of Th1/Th2 cells by homing to damaged lung tissue, thus inhibiting asthmatic airway inflammation.

[Detection and analysis of TLR2 expression on blood monocytes and B cells in patients with allergic rhinitis and asthma].

Objective To identify the expression of Toll-like receptor 2 (TLR2) on peripheral blood monocytes and B cells of patients with allergic rhinitis (AR), allergic rhinitis combined with allergic asthma (ARA) before and after allergen challenge. Methods The peripheral venous blood from patients with AR and ARA were recruited and stimulated with Artemisia sieversiana wild allergen extract (ASWE), house dust mite allergen extract (HDME), and Platanus pollen allergen extract (PPE). Flow cytometry was then used to detect the expression of TLR2 on peripheral monocytes and B cells. Results Compared with healthy control (HC) group, the percentage of TLR2+ monocytes and decreased mean fluorescence intensity (MFI) of TLR2 on monocytes in AR and ARA patients decreased. After being challenged with the above mentioned three allergens, the portion of TLR2+ monocytes in HC group and MFI of TLR2 on monocytes in AR patients also decreased. Meanwhile, MFI of TLR2 on B cells also showed a decrease after challenged with ASWE and HDME. Conclusion The expression of TLR2 on monocytes and B cells decreases in AR and ARA patients.

Prevalence of asthma in preterm and associated risk factors based on prescription data from the Korean National Health Insurance database.

We retrospectively analyzed National Health Insurance claims data (January 2002-December 2018) to determine the asthma prevalence and risk factors among preterm infants born in Korea. Patients with asthma were defined as those with a history of asthma medication prescriptions at least twice per year with International Classification of Diseases, Tenth Edition codes J45 and J46. We enrolled 99,139 preterm infants. The prevalence of asthma among preterm and term infants was 32.7% and 26.9%, 21.2% and 19.1%, 6.7% and 5.9%, 2.0%, and 1.6%, and 2.4% and 1.6% at 2, 5, 10, 15, and 16 years of age, respectively. The relative risk (RR) of asthma in preterm infants was 1.1-fold that in female preterm infants. The RR of asthma medication prescriptions for infants with extreme prematurity was 1.92-fold that of infants with moderate/late pre-term status. Among preterm with bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS) without comorbidities, the RRs for the number of asthma medication prescriptions were 1.34 and 1.06, respectively. This study revealed a higher prevalence of asthma among preterm infants than that in term infants. Male sex, extreme prematurity, BPD, and RDS were identified as risk factors for asthma medication prescriptions in preterm infants.

Particulate matter10-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression.

BACKGROUND: Particulate matter10 (PM10) can induce airway inflammation and fibrosis. Recently, chitinase-1 has been shown to play key roles in inflammation and fibrosis. We aimed to investigate the effects of chitinase-1 inhibitor in PM10-treated murine mice models. METHODS: In female BALB/c mice, PM10 was intranasally administered six times over 3 weeks, and ovalbumin (OVA) was intraperitoneally injected and then intranasally administered. Chitinase-1 inhibitor (CPX) 6 times over 3 weeks or dexamethasone 3 times in the last week were intraperitoneally administered. Two days after the last challenges, mice were euthanized. Messenger RNA sequencing using lung homogenates was conducted to evaluate signaling pathways. RESULTS: PM10 and/or OVA-induced airway inflammation and fibrosis murine models were established. CPX and dexamethasone ameliorated PM10 or PM10/OVA-induced airway hyper-responsiveness, airway inflammation, and fibrosis. CPX and dexamethasone also reduced levels of various inflammatory markers in lung homogenates. PM10 and OVA also induced changes in mRNA expression across an extreme range of genes. CPX and dexamethasone decreased levels of mRNA expression especially associated with inflammation and immune regulation. They also significantly regulated asthma and asthma-related pathways, including the JACK-STAT signaling pathway. CONCLUSIONS: Chitinase-1 suppression by CPX can regulate PM10- and OVA-induced and aggravated airway inflammation and fibrosis via an asthma-related signaling pathway.

Abdominal Pain Due to Eosinophilic Gastroenteritis Diagnosed in 25-Year-Old and 27-Year-Old Sisters with a Family History of Asthma.

BACKGROUND Eosinophilic gastroenteritis (EG) can be associated with parasitic infections, atopic drug reactions, or atopic diseases, such as asthma. This report describes 25-year-old and 27-year-old sisters with a family history of asthma who presented with abdominal pain due to EG. CASE REPORT Case 1: A 25-year-old woman presented with a 4-month history of chronic left upper quadrant abdominal pain that did not improve with proton pump inhibitor and sucralfate therapy. She has a history of asthma and allergic rhinitis. Endoscopic pathology revealed pangastritis, with eosinophilic infiltration >25 per 1 high power field. Case 2: Her 27-year-old sister was admitted with chronic abdominal discomfort in the form of vomiting and recurrent abdominal pain for the past 2 years. Treatment with proton pump inhibitors and sucralfate did not lead to improvement. She also had intermittent asthma. Pathological findings on her endoscopy showed chronic inflammation of the fundus and antrum, with eosinophilic infiltration >40 per 1 high power field. Association of eosinophilic gastrointestinal diseases in siblings has not been reported previously. CONCLUSIONS This report has highlighted that atopic disease, such as asthma, is often familial, and can be associated with generalized eosinophilia, including EG. In these 2 sisters, the clinical history and histological findings on colonic biopsy were important to confirm the diagnosis.

Epidemiological status and associated factors of frailty and pre-frailty in older adults with asthma in China: A national cross-sectional study.

Objective: There are few studies on the prevalence and factors associated with frailty and pre-frailty in older adults with asthma worldwide. The aim of this study was to examine the epidemiological status and factors associated with frailty and pre-frailty in older adults with asthma in China. Research design and methods: Data were obtained from the Sample Survey of Aged Population in Urban and Rural China in 2015, a nationwide cross-sectional survey covering 224,142 older people aged 60 years or older in 31 provinces/autonomous regions/municipalities in mainland China. We performed frailty and pre-frailty assessments using the frailty index, and the diagnosis of asthma in the older adults was self-reported based on the history of the physician's diagnosis. Results: Nine thousand four hundred sixteen older adults with asthma were included in the study. The age-sex standardized prevalence of frailty and pre-frailty in Chinese older adults with asthma was 35.8% (95% CI 34.8%-36.7%) and 54.5% (95% CI 53.5%-55.5%). Multinomial logistic regression analysis showed that increased age, female, illiteracy, living alone, poor economic status, ADL disability, comorbid chronic diseases, previous hospitalization in the past year, and residence in northern China were associated with frailty and pre-frailty in older adults with asthma. Conclusion: The prevalence of frailty and pre-frailty in Chinese older adults with asthma is very high, and assessment of frailty should become routine in the management of older adults with asthma. Appropriate public health prevention strategies based on identified risk factors for frailty in older adults with asthma should be developed to reduce the burden of frailty in Chinese older adults with asthma.

Effects of Pear Extracts on Microbiome and Immunocytokines to Alleviate Air Pollution-Related Respiratory Hypersensitivity.

Pears are ancient functional foods for modern times. Particularly, Korean pears (Pyrus pyrifolia cv.) have been used as folk medicine for respiratory diseases and have strong potential for the treatment of hazardous aerosol-related diseases. Thus, the effects of pear ethanol extracts on air pollution-related respiratory hypersensitivity were studied by toxicokinetics, pro-inflammatory cytokines, and microbiomics in preclinical and randomized double-blind clinical studies. The mild-asthma subjects, who lived in the same city, Seoul, Korea, were separated into the placebo and the treatment (pear extracts, as brix 55; arbutin 5.01 mg and chlorogenic acid 0.18 mg/3 mL per day) groups for 4 weeks (n = 20). As results, there were positive associations between urinary 2-naphthol (NT) or 1-hydroxypyrene (OHP), exposure biomarkers for polyaromatic hydrocarbons in PM2.5, and pro-inflammatory cytokines, interleukin (IL)-4 or IgE, respectively, in the human subjects. The pear extracts somewhat reduced 2-NT and 1-OHP levels. The proportions of fiber-degrading bacteria that stimulate growth of beneficial microflora for immune defense, that is, Bifidobacterium and Eubacterium, were significantly higher in the pear consuming group than in the placebo group. Moreover, pro-inflammatory cytokines, including IgE, IL-4, IL-5, and IL-13, were significantly suppressed by the pear extracts in the preclinical tests of the ovalbumin-induced asthma mice. Thus, we suggest that air pollution-related respiratory hypersensitivity can be alleviated by Korean pear extracts by modulation of microbiome and immunocytokines.

Exploring the appropriateness of prescribing practice of inhaled pharmacotherapy among Aboriginal Australians in the Top End Northern Territory of Australia: a retrospective cohort study.

BACKGROUND: Aboriginal Australians are reported to have a high burden of chronic airway diseases. However, prescribing patterns and related outcomes of airway directed inhaled pharmacotherapy, (short-acting beta agonists (SABA), short-acting muscarinic antagonists (SAMA), long-acting ß-agonists (LABA), long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS)) among Aboriginal Australian patients with chronic airway disease have been sparsely reported in the past. METHODS: A retrospective cohort study was conducted, using clinical, spirometry data, chest radiology, primary healthcare (PHC) presentations and hospital admission rates among Aboriginal patients identified to have been prescribed inhaled pharmacotherapy in remote and rural communities referred to the respiratory specialist service in the Top End, Northern Territory of Australia. RESULTS: Of the 372 identified active patients, 346 (93%) had inhaled pharmacotherapy prescribed (64% female, median age 57.7 years). ICS was the most common prescription (72% of the total cohort) and was recorded to be prescribed in 76% of patients with bronchiectasis, and 80% of patients with asthma or chronic obstructive pulmonary disease (COPD). Fifty-eight percent of patients had a respiratory hospital admission and 57% had a recorded PHC presentation for a respiratory issue during the study period, with a higher rate of hospital admissions among patients prescribed ICS compared with those on SAMA/SABA or LAMA/LABA without ICS (median rate (per person per year) 0.42 vs 0.21 and 0.21 (p=0.004). Regression models demonstrated that presence of COPD or bronchiectasis alongside ICS was associated with significantly increased hospitalisation rates (1.01 admissions/person/year (95% CI 0.15 to 1.87) and 0.71 admissions/person/year (95% CI 0.23 to 1.18) against patients without COPD/bronchiectasis, respectively). CONCLUSIONS: This study demonstrates that among Aboriginal patients with chronic airway diseases, ICS is the most common inhaled pharmacotherapy prescribed. Although LAMA/LABA and concurrent ICS use may be appropriate among patients with asthma and COPD, the use of ICS may have detrimental effects among those with underlying bronchiectasis either in isolation or concurrent COPD and bronchiectasis, potentially leading to higher hospital admission rates.

Association between serum uric acid/serum creatinine ratios and lung function in the general American population: National Health and Nutrition Examination Survey (NHANES), 2007-2012.

BACKGROUND: Assessment of lung function is essential for the early screening chronic airway diseases (CADs). Nevertheless, it is still not widely used for early diagnosing CADs in epidemiological or primary care settings. Thus, we used data from the US National Health and Nutrition Examination Survey (NHANES) to discuss the relationship between the serum uric acid/serum creatinine (SUA/SCr) ratio and lung function in general adults to gain the role of SUA/SCr in early assessment of lung function abnormalities. METHODS: From 2007 to 2012 NHANES, a total of 9569 people were included in our study. Using the regression model, XGBoost algorithm model, generalised linear model and two-piecewise linear regression model, the link between the SUA/SCr ratio and lung function was investigated. RESULTS: After correcting for confounding variables, the data revealed that forced vital capacity (FVC) declined by 47.630 and forced expiratory volume in one second (FEV1) decreased by 36.956 for each additional unit of SUA/SCr ratio. However, there was no association between SUA/SCr and FEV1/FVC. In the XGBoost model of FVC, the top five most important were glycohaemoglobin, total bilirubin, SUA/SCr, total cholesterol and aspartate aminotransferase, whereas in FEV1, were glycohaemoglobin, total bilirubin, total cholesterol, SUA/SCr and serum calcium. In addition, we determined the linear and inverse association between SUA/SCr ratio and FVC or FEV1 by constructing a smooth curve. CONCLUSIONS: In the general American population, the SUA/SCr ratio is inversely linked with FVC and FEV1, but not with FEV1/FVC, according to our research. Future studies should investigate the impact of SUA/SCr on lung function and identify possible mechanisms of action.

Distinguishing Asthma and COPD in Primary Care: A Case-based Approach.

Asthma and chronic obstructive pulmonary disease (COPD) affect more than 40 million Americans, cost more than $100 billion annually, and together constitute the fourth-leading cause of death in the United States. Distinguishing between asthma and COPD can be difficult; accurate diagnosis requires spirometry that demonstrates a characteristic pattern. Asthma is diagnosed if airway obstruction on spirometry is reversible (greater than 12% and greater than 200 mL improvement in forced expiratory volume in one second [FEV1]) with administration of bronchodilators or through the observation of bronchoconstriction (reduction in FEV1 of 20% or greater) with a methacholine challenge. COPD is diagnosed if airway obstruction (FEV1/forced vital capacity [FEV1/FVC] ratio less than 70%) on spirometry is not reversible with bronchodilators. Although not considered a separate diagnosis, asthma-COPD overlap can be a useful clinical descriptor for patients displaying diagnostic features of both diseases. In these cases, spirometry will show reversibility after administration of bronchodilators, which is consistent with asthma, and the persistent baseline airflow limitation that is more characteristic of COPD. Treatment should follow Global Initiative for Asthma guidelines and Global Initiative for Chronic Obstructive Lung Disease guidelines. In patients with asthma-COPD overlap, pharmacotherapy should primarily follow asthma guidelines, but pharmacologic and nonpharmacologic approaches specific to COPD may also be needed.

ER22/23EK AND TTH111I POLYMORPHISMS IN THE GLUCOCORTICOID RECEPTOR GENE IN PATIENTS WITH BRONCHIAL ASTHMA WITH REGARD TO THE AGE OF ONSET.

The objective of the study was to evaluate the frequency of the ER22/23EK and Tth111I polymorphisms in the glucocorticoid receptor gene (GR) in patients with early-onset and late-onset asthma (BA) and to assess the risk of its phenotype's development. We examined 553 BA patients and 95 apparently healthy individuals. The patients were divided into 2 groups depending on the age of BA onset: Group I included 282 patients with late-onset asthma, and group II included 271 patients with early-onset asthma. The ER22/23EK (rs 6189/6190) and Tth111I (rs10052957) polymorphisms in the GR gene were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Statistical analysis of obtained results was performed using SPSS-17 program. The analysis of frequency of genotypes and alleles for the ER22/23EK polymorphism in the GR gene with regard to the age of BA onset demonstrated a significant difference between patients with early-onset and late-onset asthma (p = 0.035). A significant difference was revealed in the distribution of alleles and genotypes for the Tth111I polymorphism in the GR gene between patients with early-onset BA and late-onset BA (p = 0.006). No correlation was found between the ER22/23EK polymorphism in the GR gene and late-onset BA in all genetic models; also, there was a reduction in the risk of early-onset BA observed in the dominant and additive models. No association was demonstrated between the Tth111I polymorphism in the GR gene and late-onset asthma, while a statistically significant correlation was shown with the risk of early-onset asthma in the dominant and super-dominant models. We established a significant difference in the distribution of alleles and genotypes for the ER22/23EK and Tth111I polymorphisms in the GR gene with regard to onset age; also, we found no association between these polymorphic variants and the development of late-onset asthma, but revealed a protective role of the ER22/23EK polymorphism in the GR gene in the dominant and additive inheritance models and of Tth111I polymorphism in the GR gene - in the dominant and super-dominant models.

[Pleiomorphism of the cytokine profile in nasal polyp tissue depending on the phenotype of chronic rhinosinusitis with nasal polyps]. / Pleiomorfizm tsitokinovogo profilya v tkani polipov v zavisimosti ot fenotipa polipoznogo rinosinusita.

Clinical phenotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) are characterized with different inflammation patterns of mRNA expression of cytokines and depend on presence of allergic rhinitis (AR), atopic bronchial asthma (aBA) or nonatopic bronchial asthma (nBA). OBJECTIVE: To compare inflammation response in patients with different phenotypes of CRSwNP according to level secretion of the key cytokines in nasal polyp tissue. MATERIAL AND METHODS: 292 patients with CRSwNP were divided into four phenotypes: group 1 - CRSwNP without respiratory allergy (RA) and without BA; group 2a - CRSwNP+ AR with aBA; group 2b - CRSwNP+AR without aBA; group 3 - CRSwNP+nBA. Control group (n=36) included patients with hypertrophic rhinitis without atopy or BA. Using multiplex assay we defined the level of IL-1ß, IL-4, IL-5, IL-6, IL-13, IFN-γ, TGF-ß1, TGF-ß2, TGF-ß3 in nasal polyp tissue. RESULTS: The evaluation of cytokines levels in nasal polyps in different CRSwNP phenotypes showed a pleiotropy of different cytokine secretion depending on different comorbid pathology. In control group we estimated the lowest levels of all detected cytokines in comparison with other CRS groups. High levels of local proteins IL-5 and IL-13 and low levels of all isoform of TGF-ß characterized CRSwNP without RA and BA. The combination of CRSwNP with AR showed high levels of proinflammatory cytokines IL-6 and IL-1ß, and high levels of TGF-ß1 and TGF-ß2. The combination of CRSwNP with aBA estimated low levels of proinflammatory cytokines IL-1ß, IFN-γ; in case of CRS+nBA we determined the highest levels of TGF-ß1, TGF-ß2 and TGF-ß3 in nasal polyp tissue. CONCLUSIONS: Each CRSwNP phenotype is characterized by different mechanism of local inflammation. This underlies the necessity to diagnose BA and respiratory allergy among these patients. The evaluation of local cytokine profile in different CRSwNP phenotypes can help to determine the target anticytokine therapy for patients who has low efficacy of basic corticosteroid therapy.