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INTRODUCTION: Diagnostic of aspirin (ASA) hypersensitivity is largely based on provocation tests. However, they have significant limitations including influence of medications, necessity of hospitalization, and safety issues. Basophil activation test (BAT) seems to be a promising in vitro alternative. It has already proven to be a useful tool for diagnosing IgE-mediated allergy to certain food and airborne allergens as well as insects venoms. The aim of the study was to assess performance of BAT in diagnosing aspirin hypersensitivity in comparison with current golden standard (oral provocation test, OPT). METHODS: The study group comprised 148 adult patients with suspicion of aspirin hypersensitivity, including 51 (36%) with chronic urticaria, 73 (51%) with asthma, and 55 (39%) with chronic sinusitis. The control group was 10 healthy adult patients who used NSAIDs during preceding year with good tolerance. BAT with ASA was conducted in all the participants. Additionally, in the study group, OPT was performed with cumulative dose of 1,000 mg of ASA. RESULTS: Out of 148 study group participants, 114 underwent BAT and ASA provocation with conclusive results acquired in both tests. In this group, the threshold for positive BAT was 4.9%. Sensitivity and specificity of BAT were found to be 55.9% and 75%, respectively, with a positive predictive value of 77% and a negative predictive value of 54%. The highest sensitivity (78%) was found in subgroup patients with chronic urticaria, while specificity was highest in the subgroup with chronic respiratory diseases (87%). CONCLUSION: Despite significant advantages of BAT such as safety, no influence of drugs, and objectivity, its performance makes it inferior to current standard in ASA hypersensitivity.
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INTRODUCTION: Allergen-specific immunotherapy (AIT) is the core treatment in allergic rhinitis and asthma. Although widely used, some patients do not benefit from treatment and there is no efficacy objective marker. AIM: To define the profile of gene transcripts during the build-up phase of AIT and their comparison to the control group and then search for a viable efficacy marker in relation to patient symptoms. MATERIAL AND METHODS: AIT was administered in 22 patients allergic to grass pollen. Analysis of 15 selected transcript expression was performed in whole blood samples taken before AIT (sample A) and after reaching the maintenance dose (sample B). The control group included 25 healthy volunteers (sample C). The primary endpoint was Relative Quantification. The gene expression analysis was followed by clinical evaluation with the use of Allergy Control Score (ACS). RESULTS: Comparison between samples A and B of gene expression showed a significant increase in IFNG expression (p = 0.03). In relation to the control group, pretreatment samples from patients showed higher levels of AFAP1L1 (p = 0.006), COMMD8 (p = 0.001), PIK3CD (p = 0.027) and TWIST2 (p = 0.0003) in univariate analysis. A generalized linear regression model was built according to the Bayesian Information Criterion based on the IFNG, FCER1A and PCDHB10 expression pattern for prediction of the AIT outcome. The model showed a correlation in predicted and observed changes in ACS. CONCLUSIONS: There is a significant change in the expression of IFNG during the build-up phase of AIT. The authors propose an in vitro model of AIT efficacy prediction for further validation.
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PURPOSE OF REVIEW: MicroRNAs (miRNAs) are small noncoding RNA molecules that are considered one of the fundamental regulatory mechanisms of gene expression. They are involved in many biologic processes, such as signal transduction, cell proliferation and differentiation, apoptosis and stress responses. The purpose of this review is to present recent knowledge about the role of miRNAs in asthma and outline possible applications of miRNAs. RECENT FINDINGS: A core set of miRNAs involved in asthma includes downregulated let-7 family, miR-193b, miR-375 as well as upregulated miR-21, miR-223, miR-146a, miR-142-5p, miR-142-3p, miR-146b and miR-155. Recently it has been shown that most of the involved miRNAs increase secretion of Th2 cytokines, decrease secretion of Th1 cytokines, promote differentiation of T cells towards Th2 or play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. The profiles of miRNAs correlate with clinical characteristics, including lung function, phenotype and severity of asthma. SUMMARY: Recent publications confirmed crucial regulatory role of miRNAs in the pathomechanism of asthma. Some single miRNAs or their sets hold the promise for their use as asthma biomarkers facilitating diagnosis or prediction of treatment outcomes. They are also possible target of future therapies. The studies in this field are lacking though.
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Asma/tratamento farmacológico , Asma/genética , Citocinas/metabolismo , MicroRNAs/sangue , MicroRNAs/genética , Biomarcadores/sangue , Diferenciação Celular , Epitélio/metabolismo , Perfilação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Terapia de Alvo Molecular , Miócitos de Músculo Liso/metabolismo , Linfócitos T/fisiologiaRESUMO
INTRODUCTION: Iodinated contrast media (ICM) are pharmaceuticals widely used in diagnostic procedures. Adverse effects associated with their administration are quite frequent and mostly mild. However, they raise concerns in patients and doctors in the context of their future use. AIM: To determine efficacy of premedication before medical procedures with the use of iodinated contrast media in patients with a history suggesting a hypersensitivity reaction after their past use. MATERIAL AND METHODS: Out of 152 patients consulted due to adverse reactions after ICM (85 women and 67 men, aged 43-90), 101 were selected with the history suggesting a mild hypersensitivity reaction (urticaria, itching, skin redness, malaise etc.). All the patients had health problems requiring a procedure with ICMadministration in the near future. The premedication was given with cetirizine (10 mg) and prednisone (20 mg or 50 mg, randomly assigned) 13, 7 and 1 h before the ICM administration. Presence of adverse events was compared between the subgroups with χ 2 test and efficacy of premedication - with Wilcoxon test. RESULTS: Seventy-six patients underwent the radiologic procedure with premedication with antihistamine and a lower (40 patients) or higher dose (36 patients) of prednisone. Four of them reported a cutaneous hypersensitivity reaction (urticaria, itching, redness) and one - dyspnoea. There was no statistically significant difference in relation to the premedication protocol (p = 0.1306). CONCLUSIONS: Premedication with cetirizine and prednisone before radiologic procedures proved to be efficient in patients with a history suggesting hypersensitivity to iodinated contrast media. There was no significant difference in efficacy related to the dose of prednisone (20 mg vs. 50 mg).
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MicroRNAs are small non-coding molecules playing a significant regulatory role in several allergic diseases. However their role in tolerance induction remains unclear. The aim of this study was to determine the expression of selected microRNAs during the first three months of wasp venom immunotherapy (VIT). 5 adult patients with a history of severe systemic reactions after stinging by wasps and confirmed sensitization were included. Venous blood samples were collected before VIT, 24 hours after completing its initial phase and after 3 months of the maintenance therapy. A control group was comprised of 5 healthy individuals with no history of allergy. In the blood samples expression of 96 microRNAs was determined with the use of microfluidic cards. In a statistical analysis the expression was compared between the study groups as well as between the pre- and post-VIT samples. Significant differences were found between the patients with wasp venom allergy and the healthy controls in the expression of miR-601 and miR-1201 upregulated in allergic patients at every time point (p = 0.04; p = 0.015, respectively). During VIT profile of microRNA was changing with lower expression of 6 microRNAs (including miR-182, miR-342, miR-375) and higher of 11 microRNAs (including let-7d, miR-34b, miR-143). To conclude, VIT has led to some changes in the expression of microRNA associated with Th2-type inflammation and tolerance induction.
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Mordeduras e Picadas/imunologia , Expressão Gênica/imunologia , Imunoterapia/métodos , MicroRNAs/genética , Venenos de Vespas/imunologia , Vespas/imunologia , Adulto , Animais , Dessensibilização Imunológica/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Venenos de Vespas/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Histoplasmosis is a mycosis caused by soil-based fungus Histoplasma capsulatum endemic in the USA, Latin America, Africa and South-East Asia. The disease is usually self-resolving, but exposure to a large inoculum or accompanying immune deficiencies may result in severe illness. Symptoms are unspecific with fever, cough and malaise as the most common. Thus, this is a case of disease which is difficult to diagnose and very rare in Europe. As a result, it is usually not suspected in elderly patients with cough and dyspnea. CASE PRESENTATION: This is a case of a 78-year-old patient, admitted to our department due to respiratory failure, cough, shortness of breath, fever and weight loss with no response to antibiotics administered before the admission. Chest CT revealed numerous reticular and nodular infiltrations with distribution in all lobes. The cytopathology of BAL showed small parts of mycelium and numerous oval spores. Considering clinical presentation and history of travel to Mexico before onset of disease, pulmonary histoplasmosis was diagnosed. After introduction of antifungal treatment rapid improvement was achieved in terms of both clinical picture and respiratory function. CONCLUSIONS: Since the risk of Histoplasma exposure in Europe is minimal, patients, who present with dyspnea, fever and malaise are not primarily considered for diagnosis of histoplasmosis. However, taking into account increasing popularity of travelling, also by elderly or patients with impaired immunity, histoplasmosis should be included into differential diagnosis.
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Histoplasma/isolamento & purificação , Histoplasmose/diagnóstico por imagem , Pneumopatias Fúngicas/diagnóstico por imagem , Viagem , Idoso , Antifúngicos/uso terapêutico , Diagnóstico Diferencial , Histoplasmose/tratamento farmacológico , Humanos , Pneumopatias Fúngicas/tratamento farmacológico , Masculino , México , Polônia , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Allergen specific immunotherapy (AIT) is the only treatment modifying the course of the disease in patients allergic to airborne allergens. It has been proven to be effective in allergic populations, however individual patients vary in terms of response to the therapy. AIM: To assess the factors that might affect the efficacy of AIT. MATERIAL AND METHODS: Patients treated with AIT for grass pollen or house dust mites were included. The efficacy of AIT was assessed with the use of Allergy Control Score (ACS), performed before and at least 1 year after AIT. The following variables were assessed as potential risk factors for a worse response to AIT: age, gender, type of allergy, type of allergen, type of vaccine, type of AIT and smoking history. RESULTS: The study group consisted of 145 subjects.AIT was effective in the entire group; the mean ACS results decreased from 21.14 to 14.41 points (p< 0.0001). No differences in efficacy in terms of assessed risk factors were found, except for smoking history (ACS change in the smoking group was smaller: from 21.8 to 18.1 points; p = 0.09, OR = 0.323; 95% CI: 0.11-0.88; p = 0.02). CONCLUSIONS: Smoking history may affect AIT outcomes.
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BACKGROUND: Allergen-specific immunotherapy is the most effective method of treatment in allergy to wasp venom. However, its mechanism of action is still not fully understood. The aim of this study is to describe changes in microRNA (miRNA) expression in patients undergoing the buildup phase of venom immunotherapy. METHODS: The study group comprised 7 adult patients with a history of severe systemic reactions after stinging by a wasp. In all patients, sensitization to wasp venom had been confirmed by skin tests and serum IgE. The buildup phase of wasp venom immunotherapy (VIT) was conducted according to an ultrarush protocol. In blood samples collected before and 24 h after completing the VIT buildup phase, 740 miRNAs were assessed. RESULTS: Of the 740 miRNAs, 440 were detected in the study group, and in 5 expression was significantly changed after the buildup phase of VIT: miR-370, miR-539, miR-502-3p, miR-299, and miR-29c. Another 62 miRNAs changed 2-fold in some patients (nonsignificant), including increases in miR-143 (stimulating FOXp3 expression) and let-7d (reducing expression of IL-13, IL-6, and TLR4), and decreases in proinflammatory miR-301, miR-146b, miR-106, and miR-485. CONCLUSIONS: Several changes in miRNA expression have been found as a result of the buildup phase of wasp VIT, with lower expression of some miRNAs involved in allergic inflammation and higher expression of those possibly involved in tolerance induction. However, the role of the most significant changes is uncertain.
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Dessensibilização Imunológica , Regulação da Expressão Gênica , Mordeduras e Picadas de Insetos/genética , Mordeduras e Picadas de Insetos/terapia , MicroRNAs/genética , Venenos de Vespas/administração & dosagem , Vespas , Adulto , Idoso , Animais , Feminino , Perfilação da Expressão Gênica , Humanos , Tolerância Imunológica , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
INTRODUCTION: A history of an adverse reaction to amoxicillin, irrespective of the mechanism involved, significantly elevates patients' anxiety and affects therapeutic decisions in the future, leading to unnecessary avoidance of antibiotics. As a consequence, it would be useful to find a safe and reliable protocol for typing safe alternative antibiotics. The aim of the study was to determine negative predictive value of typing safe antibiotic in patients with a history of hypersensitivity reaction to amoxicillin. MATERIAL AND METHODS: 71 patients, aged 20-83, with a history of an adverse reaction to amoxicillin were retrospectively analysed. On the basis of the reaction type they were divided into three groups: A - symptoms not typical for hypersensitivity reactions, B - allergy manifested by urticaria and/or angioedema, C - anaphylaxis. In group A amoxicillin was tested, in group B - cefuroxime, and in group C - macrolide: azithromycin or clarithromycin. Telephone follow-up visits were performed twice: 6-12 months and 3-5 years after the clinical assessment to evaluate tolerance of antibiotics. On the basis of the follow-up results, the negative predictive value (NPV) of the protocol was calculated. RESULTS: The full diagnostic protocol was applied in 62 participants. Amoxicillin was found safe in 22, cefuroxime - in 21 and macrolide - in 19 patients. No anaphylactic reactions were observed during the tests. On the basis of the telephone follow-up, the NPV of the protocol was 96% in the first follow-up and 97% in the second one. CONCLUSION: A stepwise approach including SPTs, ICTs and provocations with amoxicillin / cefuroxime/macrolide - depending on a patient's history - is safe and allows typing an antibiotic in the vast majority of patients.
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Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/prevenção & controle , Administração Oral , Adulto , Idoso , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Protocolos Clínicos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Differentiating between cross-reactivity and double sensitization is still a challenging issue in allergology. AIM: To differentiate cross-reactions accompanying latex allergy with the use of the ISAC test. MATERIAL AND METHODS: Thirty-nine patients reporting immediate allergic reactions to latex were enrolled into the study (group A). The control group was comprised of 41 patients with allergic diseases not associated with latex (group B) and 20 healthy individuals (group C). Their history was recorded and skin prick tests were performed with latex, airborne and food allergens. Specific IgE against food allergens, latex (k82) and recombined latex allergens were determined. ImmunoCAP ISAC test was performed with 103 molecules. RESULTS: Sensitization to latex was found by means of skin tests in 16 cases and sIgE against latex was revealed in 12 cases (including 10 positive in both SPT and sIgE). In the ISAC test antibodies against recombined latex allergens were found in 8 patients with rHev b 6 as the most common. All the patients positive for rHev b 1, 5, 6, 8 had allergy or asymptomatic sensitization to food allergens cross-reacting with latex. Some reactions could not have been differentiated due to the lack of allergens in the ISAC test. Others, not related to latex-fruits syndrome were explained by cross-reactivity with other profilins or PR-10 proteins. CONCLUSIONS: ImmunoCAP ISAC test could be useful in differentiating between cross-reactions and double sensitizations. However, in the case of latex its advantages are limited due to a small panel of allergens.
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PURPOSE: YKL-40 is a chitinase-like protein found to correlate with asthma as well as numerous infectious and autoimmune diseases or cancer. The aim of the present study was to investigate the role of YKL-40 as a possible marker of asthma and its associations with factors differentiating phenotypes of asthma. METHODS: The study group comprised 167 patients, including 116 women and 51 men aged 18-88 years with chronic asthma. The control group comprised 81 healthy individuals, including 50 women and 31 men aged 19-86 years. In every participant, medical history was taken; spirometry and skin prick tests were performed. YKL-40 was determined in sera by means of ELISA test. RESULTS: Mean serum YKL-40 level was 59.7 ng/ml (53.6-65.7 ng/ml; 95% CI) with significant difference between asthmatics and healthy controls (mean values: 66.8 ± 53.8 vs. 44.9 ± 29.4 ng/ml; p < 0.001). In asthmatics, the level was significantly higher in subgroup with poor control of symptoms and exacerbations (91.8 ± 57.1 ng/ml) compared to stable asthmatics (59.6 ± 50.8 ng/ml; p < 0.001) as well as in atopic compared to non-atopic asthmatics (77.2 ± 53.9 vs. 61.1 ± 57.8 ng/ml; p < 0.001). Mean YKL-40 level in obese asthmatics was 135.6 ng/ml compared to 50.0 ng/ml in non-obese (p < 0.001). When phenotypes of early-onset atopic, late-onset non-atopic, and obesity-related asthma were compared, YKL-40 levels were 80.62 ± 46.9, 51.5 ± 24.9, and 168.1 ± 71.5 ng/ml, respectively (p < 0.05). CONCLUSION: Although YKL-40 is not a specific marker for asthma, it correlates with some clinical features such as exacerbation, level of control, atopy, and obesity.
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Adipocinas/sangue , Asma/sangue , Hipersensibilidade Imediata/sangue , Lectinas/sangue , Obesidade/sangue , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Asma/complicações , Asma/fisiopatologia , Biomarcadores/sangue , Estudos de Casos e Controles , Proteína 1 Semelhante à Quitinase-3 , Progressão da Doença , Feminino , Humanos , Hipersensibilidade Imediata/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Fenótipo , Adulto JovemRESUMO
In the face of increasing prevalence of hypersensitivity reactions, introduction of effective, reliable and safe methods plays a crucial role in their diagnosing. Among the currently available laboratory (in vitro) methods is basophil activation test (BAT). It is a flow- cytometry based assay that allows to identificate in the blood sample basophils and additionally to asses the degree of cell activation after exposure to an antigen. The most common superficial identification markers are CD63 and CD203c, which increase in number after activation. Basophil actvation test can be applied to confirm diagnosis of allergy to Hymenoptera venoms, food, pollens and hypersensitivity to drugs. The aim of present paper is to present theoretical methods of this test as well as its pros and cons. We focus also on presentation of clinical case where BAT seemed to be a necessary addition to a routine diagnostic pathway. We present a case of identification of the culprit drug which caused an anaphylactic reaction.
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Anti-Inflamatórios não Esteroides/imunologia , Aspirina/imunologia , Basófilos/imunologia , Hipersensibilidade a Drogas/diagnóstico , Testes Imunológicos/métodos , Sensibilidade e EspecificidadeRESUMO
Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients' survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace's crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace's cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis.
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BACKGROUND: Although allergy to local anesthetics (LA) is rare, patients often report unwanted reactions after their administration. A history of anaphylaxis or an atypical reaction related to LA is an indication for typing a safe anesthetic for future surgical or dental procedures. AIM: The aim of the study was to determine the negative predictive value (NPV) of typing safe LA. METHODS: A total of 154 patients with a history of an unwanted reaction to LA were enrolled into the study. Stepwise typing of a safe anesthetic included skin prick tests (SPT) and intracutaneous tests (ICT) with two or three of the following LA: lidocaine, bupivacaine, mepivacaine, and articaine. Skin tests were followed by provocations with one or two LA. Telephone follow-up visits were performed 4-12 months after drug typing. On the basis of follow-up questionnaire results, the NPV of the protocol was calculated. RESULTS: The full protocol was performed in 148 patients. Positive results of SPT were observed in 2, of ICT in 19 and of provocations in 11 cases. Lidocaine was found safe in 44, bupivacaine in 14, mepivacaine in 34 and articaine in 61 patients. The drug typed at the clinical visit was administered in 78 patients, and 76 reported no reactions (NPV = 97%). CONCLUSION: Stepwise approach including SPT, ICT and provocations is safe and allows typing a safe anesthetic in a vast majority of patients.
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Anestésicos Locais/imunologia , Hipersensibilidade a Drogas/diagnóstico , Anestésicos Locais/efeitos adversos , Anestésicos Locais/classificação , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Testes CutâneosRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) is associated with elevated risk of cardiovascular events. The early stages of vascular complications can be visualized by means of ultrasound. Intima-media thickness (IMT) correlates with the presence of risk factors of cardiovascular diseases such as hypertension, diabetes, tobacco smoking, or hyperlipidemia. However, little is known whether OSA itself may be the cause of IMT thickening. METHODS: The study group was composed of 28 patients (6 women, 22 men; mean age = 53.8 years, mean BMI = 27.1 kg/m(2), mean AHI = 22.4/h) with OSA who had no comorbidities. The control group consisted of 28 healthy subjects (6 women, 22 men; mean age = 53.9 years; mean BMI = 27.5 kg/m(2)). In both groups IMT was assessed in common carotid arteries with the use of ultrasonography. Additionally, in patients with OSA, pulse wave velocity, echocardiography, 24-h automated blood pressure monitoring, clinical signs and symptoms, and blood tests were performed to investigate possible correlations with IMT. RESULTS: Median IMT was 0.41 mm in OSA patients and 0.46 mm in the control group (p = 0.087). Echocardiography revealed left ventricle hypertrophy in 21%, systolic disorders in 8%, and diastolic disorders in 57% of the patients. In a large majority of patients, pulse wave velocity was found to be normal. IMT correlated with age (r = 0.446, p = 0.017), total cholesterol (r = 0.518, p = 0.005), daytime systolic blood pressure (r = 0.422, p = 0.025), pulse pressure 24 h and daytime (r = 0.424, p = 0.027 and r = 0.449, p = 0.019), early mitral flow/atrial mitral flow (E/A) (r = -0.429, p = 0.023), and posterior wall diameter (PWD) (r = 0.417, p = 0.270). CONCLUSION: In a relatively nonobese group of patients, no significant differences were found in the intima-media thickness between OSA patients without concomitant cardiovascular diseases and healthy controls. This may lead to the conclusion that IMT does not reflect increased risk of cardiovascular events in patients with isolated OSA.
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Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Espessura Intima-Media Carotídea , Apneia Obstrutiva do Sono/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Valor Preditivo dos Testes , Fatores de Risco , Apneia Obstrutiva do Sono/diagnósticoRESUMO
Osteocalcin is the most important noncollagenous protein component of the bone. Polymorphisms of osteocalcin gene were reported to be associated with bone mineral density. However, this relation was only confirmed in some populations. In this study presence of C/T polymorphism in osteocalcin gene (rs1800247) was determined in Kashubian population (northern Poland). The frequencies of variants were CC 9 %, TC 31 %, and TT 60 %, with no significant differences between genders. The genotypes were in Hardy-Weinberg equilibrium.
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Osteocalcina/genética , Osteoporose/etnologia , Osteoporose/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Regiões Promotoras Genéticas/genética , Fatores Sexuais , Adulto JovemRESUMO
Asthma is a heterogeneous chronic disorder of the airways, with inflammation and bronchial hyperresponsiveness as its major underlying phenomena. Asthmatics vary in terms of inflammation pattern, concomitant pathologies, and factors aggravating the course of the disease. As a result, there is a need for sensitive and specific biomarkers that could facilitate diagnosing asthma as well as phenotyping in everyday practice. Chitinases and chitinase-like proteins (CLPs) seem promising in this field. Chitinases are evolutionarily conserved hydrolases that degrade chitin. In contrast, CLPs bind chitin but do not have degrading activity. Mammalian chitinases and CLPs are produced by neutrophils, monocytes, and macrophages in response to parasitic or fungal infections. Recently, several questions have been raised about their role in chronic airway inflammation. Several studies demonstrated that overexpression of CLP YKL-40 was associated with asthma. Moreover, it correlated with exacerbation rate, therapy resistance, poor control of symptoms, and, inversely, with FEV1. YKL-40 facilitated allergen sensitization and IgE production. Its concentration was elevated in bronchoalveolar lavage fluid after an allergen challenge. It was also found to promote the proliferation of bronchial smooth muscle cells and correlate with subepithelial membrane thickness. Thus, it may be involved in bronchial remodeling. Associations between YKL-40 and particular asthma phenotypes remain unclear. Some studies showed that YKL-40 correlates with blood eosinophilia and FeNO, suggesting a role in T2-high inflammation. Quite the opposite, cluster analyses revealed the highest upregulation in severe neutrophilic asthma and obesity-associated asthma. The main limitation in the practical application of YKL-40 as a biomarker is its low specificity. High serum levels of YKL-40 were also found in COPD and several malignancies, in addition to infectious and autoimmune diseases. To conclude, the level of YKL-40 correlates with asthma and some clinical features in the whole asthmatic population. The highest levels are found in neutrophilic and obesity-related phenotypes. However, due to its low specificity, the practical application of YKL-40 remains uncertain but could be useful in phenotyping, especially when combined with other biomarkers.
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Background: Subcutaneous immunotherapy (SCIT) is widely used in the treatment of allergic rhinitis (AR). This study aimed to determine the expression of 48 miRNAs in patients with AR undergoing grass pollen SCIT and investigate relations with clinical outcomes. Methodology: Expression of selected miRNAs was determined using RT-PCR in the full blood of 16 patients with AR and seven healthy controls. Results: miR-136, miR-208 and miR-190 were upregulated in the AR group. After 6 months of SCIT, significant downregulation of some proinflammatory miRNAs and upregulation of several miRNAs regulating Th1/Th2 balance were found. No differences were found between good and poor responders. Conclusion: miRNAs may play a regulatory role in SCIT, leading to tolerance induction.
Background: Subcutaneous immunotherapy is widely used in the treatment of allergic rhinitis (AR). MicroRNAs (miRNAs) are small molecules controlling gene expression. Their role in the process of immunotherapy is not yet well understood. This study aimed to investigate the expression of 48 miRNAs in patients with AR undergoing grass pollen immunotherapy and relations between miRNAs and clinical outcomes. Methodology: The expression of selected miRNAs was determined in the blood of 16 patients with AR and seven healthy people. Results: Three miRNAs were found to be overproduced in allergic patients. During immunotherapy, the production of several proinflammatory miRNAs was reduced while those responsible for allergen tolerance were produced in larger amounts. Conclusion: miRNAs may play an important role in immunotherapy, leading to better tolerance of allergens.
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MicroRNAs , Rinite Alérgica Sazonal , Rinite Alérgica , Imunoterapia Sublingual , Alérgenos/genética , Alérgenos/uso terapêutico , Dessensibilização Imunológica , Humanos , Fatores Imunológicos/uso terapêutico , Injeções Subcutâneas , MicroRNAs/genética , MicroRNAs/uso terapêutico , Poaceae/genética , Pólen/genética , Rinite Alérgica/genética , Rinite Alérgica/terapia , Rinite Alérgica Sazonal/terapiaRESUMO
BACKGROUND: Gaining asthma control is still a challenge in a large number of patients. It could be facilitated by using biomarkers indicating the grade of inflammation and correlating with clinical picture. Chitinases and chitinase-like proteins play a role in Th2-type inflammation. Thus, they may be useful in diagnosing and monitoring of asthma. OBJECTIVES: The aim of the study was to investigate the relevance of YKL-40 as a good biomarker of asthma, its control, and severity. METHODS: Level of YKL-40 was determined by means of immunoassay in sera of 59 asthmatics (39 women, 20 men, aged 23-76 years) and 29 healthy controls (18 women, 11 men, aged 20-80 years). Asthma severity and control were assessed according to GINA guidelines. Differences between groups were compared with the use of Mann-Whitney's U-test. Correlations between variables were assessed with Pearson's test. RESULTS: Symptoms of asthma were found to be controlled in 12 (20%), partly controlled in 17 (29%), and uncontrolled in 30 (51%) patients. YKL-40 levels were significantly higher, on average, in asthmatics compared to control group (median levels: 125.3 U and 84.1 U, respectively, p < .001). YKL-40 correlated with the number of blood eosinophils (r = 0.376, p = 0.05). However, no relations have been found between YKL-40 level and asthma severity, control, or total serum IgE (r = -0.05, p = .05). CONCLUSION: YKL-40 seems to be a good marker of asthma. However, its level may not correlate with clinical outcome.
Assuntos
Adipocinas/sangue , Asma/imunologia , Lectinas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/sangue , Biomarcadores/sangue , Proteína 1 Semelhante à Quitinase-3 , Eosinofilia/sangue , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Adulto JovemRESUMO
The influence of respiratory infections on asthma has not been fully understood. Acute viral and bacterial infections often lead to exacerbations. Less is known about the role of chronic infections, particularly with atypical pathogens. The aim of this study was to evaluate the impact of Chlamydophila pneumoniae and Mycoplasma pneumoniae infections on the control and severity of asthma. Spirometry, skin-prick tests as well as measurement of immunoglobulin G (IgG), IgM, and IgA against C. pneumoniae and M. pneumoniae (ELISA) were performed in 95 patients with persistent asthma and 58 healthy controls. Additionally, in the selected group of asthmatic patients, presence of C. pneumoniae and M. pneumoniae genetic material was tested in induced sputum (polymerase chain reaction [PCR]). IgA against C. pneumoniae was found in 42 (44.2%) asthmatic patients and 17 (29.3%) controls (p < 0.05). It was found more often in the group with uncontrolled asthma (p = 0.001) as well as in nonatopic asthmatic patients (p < 0.05). IgG was detected in 58 asthmatic patients (61%) and 21 (36.2%) controls, more often in cases of uncontrolled (p < 0.05) and nonatopic asthma patients (p < 0.05). Such correlations were not found in relation to M. pneumoniae infections. C. pneumoniae was detected by means of PCR in respiratory secretions of eight asthmatic patients (40%), and M. pneumoniae was detected in two asthmatic patients (10%). In conclusion, C. pneumoniae infections are more frequent in asthmatic patients compared with healthy individuals and in nonatopic asthmatic patients compared to atopic patients. Chronic infection is associated with poor control of asthma.