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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: Self-management is an appealing strategy for prevention of asthma exacerbations. This study aimed to evaluate the feasibility and safety of a portable spirometer for unsupervised home spirometry measurements among patients with asthma. METHODS: A multi-center, prospective, single-arm, open study recruited 86 patients with controlled or partly controlled asthma (41 women, 38.6 ± 10.4 y/o and 45 men, 36.2 ± 12.1 y/o). After a training session, patients performed daily spirometry at home with the AioCare® mobile spirometry system. Each spirometry examination was recorded and evaluated according to the ATS/ERS acceptability and repeatability criteria. The primary endpoint was defined as three or more acceptable examinations in any given seven-day period (+/- 1 day) during any of the three weeks of the study. The system allowed for online review of measurements by physicians/nurses to provide feedback to patients. RESULTS: Of 78 patients with complete data, 67 (86%) achieved the primary endpoint. Seventy-five (96%) participants used the device correctly once or more, and 10 (13%) patients succeeded every single day over the three-week follow-up. The rate of acceptable spirometry examinations differed between the sites (p = 0.013). Retraining was required in 20 of 62 (32%) eligible patients, and successful in 8 individuals (40%). Satisfaction with the AioCare® system was high, 90% of respondents perceived it as useful and user-friendly. CONCLUSIONS: Self-monitoring of asthma with a connected mobile spirometer is feasible, safe and satisfactory for patients with asthma. It remains to be established whether unsupervised home spirometry measurements may improve early diagnosis and outcomes of self-management in cases of exacerbation or loss of asthma control.
Highlights BoxThis study aimed to evaluate the ability of patients with asthma to perform high-quality daily spirometry examinations at home with using the AioCare® mobile spirometry system. The study showed that unsupervised home spirometry is safe and feasible in patients with asthma. Most patients used the device on most days of the study, and nearly 90% of all patients achieved the primary endpoint. There were no device-related adverse events.
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Asma/fisiopatologia , Monitorização Ambulatorial/instrumentação , Espirometria/instrumentação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , AutogestãoRESUMO
Severe asthma requires at least high doses of inhaled corticosteroids (ICS) in combination with a long-acting ß-agonist (LABA) or systemic corticosteroids (SCS) for more than 50% of days/year to avoid loss of control, or remains uncontrolled despite the treatment described above. The diagnosis of severe asthma should be confirmed in a reference centre as it requires careful differential diagnosis and the exclusion of factors hindering the achievement of optimal control. Severe asthma represents a significant burden for the patient, their family and the healthcare system. This is due to the severity of the symptoms, drug costs, significant impairment of everyday functioning and life quality, and limitation in the professional work. In the case of ineffectiveness of the step 4 GINA treatment, the patient should be referred to a specialist centre to consider additional treatment, including anti-IgE receptor (omalizumab), anti-IL-5 receptor (mepolizumab), or an antibody directed against the α-subunit of receptor for IL-5 (benralizumab). In the case of severe asthma, intensification of therapy should first of all include biological therapy and not the use of SCS. Biological drugs are available in Poland as a part of the therapeutic programme for the treatment of severe asthma. In practice, the therapeutic programme may change with subsequent notices of the Ministry of Health and does not have to be consistent with the Summary of Product Characteristics for individual preparations. The current review presents the basic principles of differential diagnosis of severe asthma and the selection of the optimal biological therapy in Polish conditions.
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INTRODUCTION: Progressing deterioration of the lung function, dyspnoea, cough, wheezing and chest tightness are the main features of asthma exacerbations. The first step in the prevention of severe asthma exacerbations is to intensify the anti-inflammatory treatment with high doses of inhaled corticosteroids (ICS). AIM: To assess the efficacy of ciclesonide in patients who have been losing control of asthma despite being treated with medium doses of inhaled corticosteroids and long-acting ß2-agonists (LABA) as the second controller. MATERIAL AND METHODS: The study was conducted in a group of 74 asthmatic patients who have been losing control of their asthma. Subjects entering the study received the following anti-inflammatory interventions: high doses of ciclesonide (1280 µg) or 640 µg of ciclesonide added to a current dose of ICS or a doubled dose of current ICS. RESULTS: Treatment options containing ciclesonide have shown statistically and clinically important advantages (improvement of Asthma Control Test score, reduction in rescue medication consumption, reduction in day and night symptoms score, improvement in spirometry parameters, decrease in exhaled nitric oxide, and no necessity of oral corticosteroids treatment) in comparison to patients for whom medium doses of the previously used inhaled corticosteroid were doubled. CONCLUSIONS: Treating with high doses of ciclesonide is characterised by a quick and potent anti-inflammatory effect as well as prompt clinical improvement along with the proper safety profile in patients experiencing asthma exacerbations.
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Anaphylaxis is defined as severe, life-threatening, systemic or general, immediate reaction of hypersensitivity, with repeatable symptoms caused by the dose of stimulus which is well tolerated by healthy persons. The proper diagnosis, immediate treatment and differential diagnosis are crucial for saving patient's life. However, anaphylaxis is relatively frequently misdiagnosed or confused with other clinical entities. Thus, there is a continuous need for identifying detectable markers improving the proper diagnosis of anaphylaxis. Here we presented currently known markers of anaphylaxis and discussed in more detail the most clinically valuable ones: tryptase, platelet activacting factor (PAF), PAF-acethylhydrolase, histamine and its metabolites.
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Anafilaxia/metabolismo , Biomarcadores/metabolismo , Anafilaxia/diagnóstico , Anafilaxia/genética , Histamina/metabolismo , Humanos , Fator de Ativação de Plaquetas/metabolismo , Triptases/metabolismoRESUMO
BACKGROUND/AIMS: Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. METHODS: Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays. RESULTS: Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin. CONCLUSIONS: Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.
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Toxina da Cólera/sangue , Inflamação/sangue , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/complicações , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Haptoglobinas , Hepcidinas/sangue , Humanos , Inflamação/complicações , Interleucina-6/sangue , Ferro/sangue , Pessoa de Meia-Idade , Precursores de Proteínas , Receptores da Transferrina/sangue , Insuficiência Renal Crônica/complicaçõesRESUMO
INTRODUCTION: Fibroblast growth factor 23 (FGF-23) levels are elevated in impaired renal function. Inflammation and iron are potential regulators of FGF-23. The aim of the study was to evaluate the association between FGF-23 concentration, novel iron status biomarkers and inflammatory parameters among patients with early stages of chronic kidney disease (CKD). MATERIAL AND METHODS: The study population included 84 patients with CKD in the early stage. Serum hemoglobin, fibrinogen, creatinine, iron, transferrin saturation and ferritin levels were measured using standard laboratory methods. Commercially available kits were used to measure: intact FGF-23, hepcidin, soluble transferrin receptor (sTfR), interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). RESULTS: In patients with CKD no differences in FGF-23 concentration according to iron status were observed. Lower iron concentration was associated with higher concentrations of hsCRP, IL-6 and fibrinogen. In univariate and multivariate analysis FGF-23 correlated with fibrinogen (r = -0.23, p < 0.05) and eGFR (r = -0.36, p < 0.05). CONCLUSIONS: FGF-23 is affected by kidney function and fibrinogen but not iron status parameters in the early stages of CKD. Our data are paving the way for further studies on the role of FGF-23 in iron metabolism, especially in early stages of CKD.
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OBJECTIVE: Asthma enhances the risk of pulmonary embolism. The mechanism of this phenomenon is unclear. METHODS: We evaluated the kinetics of clot formation, clot retraction rate (CRR), clot volume at 40 min, the rate of lactate production (a marker of aerobic glycolysis in platelets in contracting clots), blood eosinophil count (EOS), nitric oxide in exhaled breath (FENO), and spirometry (FEV1) in 50 healthy controls and in 81 allergic asthmatics (41 subjects with steroid-naïve asthma and 40 with steroid-treated asthma). RESULTS: Thromboelastometry revealed that only steroid-treated asthmatics had slightly activated coagulation. Compared with healthy controls, whole asthmatics demonstrated (p < 0.05) reduced CRR, higher clot volume at 40 minutes, higher FENO, decreased FEV1, elevated EOS, and augmented lactate production in retracting clots. Reduced CRR was observed also in the absence of native plasma. In whole study population (asthmatics and healthy controls), CRR positively correlated with spirometry (rS = 0.668, p = <0.001) and negatively with FENO (rS = -0.543; p < 0.001), EOS (rS = -0.367, p < 0.002), and lactate production (rS = -0.791; p < 0.001). However, in steroid-treated asthmatics, the CRR did not correlate with FENO and EOS. In all study patients lactate production negatively correlated with FEV1 and positively with FENO. CONCLUSION: Collectively, this data is consistent with the hypothesis that, in asthmatics, reactive nitrogen species produced in the lungs may reduce platelet contractility (and CRR) through the diminution of platelet energy production. CRR inhibition would predispose asthmatics to pulmonary embolism.
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Asma/sangue , Plaquetas/metabolismo , Retração do Coágulo/fisiologia , Trombose/metabolismo , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Adulto , Idoso , Asma/tratamento farmacológico , Estudos de Casos e Controles , Retração do Coágulo/efeitos dos fármacos , Eosinófilos/metabolismo , Feminino , Humanos , Ácido Láctico/metabolismo , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Testes de Função Respiratória , Tromboelastografia , Adulto JovemRESUMO
PURPOSE: The aim of the study was to assess GDF-15 and iron status in patients in early stages of chronic kidney disease with a particular emphasis on elderly population in association of classic iron status parameters with novel iron homeostasis biomarkers and inflammatory parameters. METHODS: Serum concentrations of GDF-15, iron (Fe), transferrin saturation, soluble transferrin receptor (sTfR), hepcidin, high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6), and hemoglobin were measured in 56 patients ≥65 years of age and in 31 <65 years of age. RESULTS: In patients ≥65 years, serum concentrations of GDF-15 and hsCRP were significantly higher in comparison with younger group. There was no statistically significant difference in hemoglobin, iron, hepcidin, and sTfR concentration between the two studied groups. In both groups GDF-15 was significantly correlated with hemoglobin, eGFR, hsCRP, and IL-6. GDF-15 was significantly higher in patients with anemia in comparison with their non-anemic counterparts. In multivariate analysis, hemoglobin was found to be a predictor of log GDF-15 (beta value = 0.36, P = 0.006, R (2) = 37 %). CONCLUSIONS: An intricate interplay between renal function, anemia, and GDF-15 concentrations awaits further studies, as there are few data regarding pathophysiological role of GDF-15 in diabetes, kidney disease, and other comorbidities. Further understanding regarding the signaling pathways of GDF-15 may help to discover next pieces in the exciting puzzle of GDF-15. Finally, as studies dealing with normal level of GDF-15 in the healthy aged are lacking, it is possible that the higher values of GDF-15 values found in the present study represent values of GDF-15 according to age more than CKD levels.
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Fator 15 de Diferenciação de Crescimento/sangue , Ferro/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Hemoglobinas/metabolismo , Hepcidinas/sangue , Humanos , Inflamação , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Receptores da Transferrina/sangue , Transferrinas/sangueRESUMO
BACKGROUND: Recently, identification of CD25 (interleukin-2 receptor alpha) expression on leukemic blasts was correlated to early treatment failure and unfavorable outcome in acute myeloid leukemia (AML) patients. Here we wished to determine whether quantification of CD25 on peripheral blood CD4+ T cells could improve prognostication in newly diagnosed AML patients. METHODS: The mean fluorescence intensity (MFI) of CD25 expression and frequencies of peripheral blood CD4+ T cells with varying levels of CD25 and CD127 expression were assessed by flow cytometry in all studied individuals. RESULTS: Using univariate (unadjusted) and multivariate (adjusted) analyses we demonstrated that detection of high pretreatment CD25 expression on circulating CD4+ T cells was associated with significantly decreased survival rate of AML patients subjected to standard induction chemotherapy. These associations held true for both entire group of analyzed AML patients and different subgroups of patients identified by presence or absence of favorable and adverse molecular prognostic factors. CONCLUSIONS: Our data indicate that quantification of CD25 expression on peripheral blood CD4+ T cells could become a novel, easily accessible method of shortened survival prognostication of AML patients subjected to standard cytotoxic therapy.
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Linfócitos T CD4-Positivos/metabolismo , Quimioterapia de Indução/mortalidade , Quimioterapia de Indução/tendências , Subunidade alfa de Receptor de Interleucina-2/biossíntese , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Adulto , Idoso , Feminino , Citometria de Fluxo/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taxa de Sobrevida/tendênciasRESUMO
The main objective of asthma treatment is to control symptoms of the disease; however, despite the availability of guidelines and many groups of medications, the degree of control of this condition is insufficient. In difficult-to-treat asthma, the optimal control cannot be achieved due to reasons independent of the disease. Factors worsening asthma control include: inadequate treatment plan (low therapy adherence and compliance), inappropriate inhalation technique, insufficient symptom control using the available classes of medications, incomplete response to treatment (non-responders, steroid-resistance), incorrect diagnosis of asthma or comorbidities, and environmental factors. In order to achieve the optimal asthma control, it is recommended to: take therapeutic decisions with the patient, assess the probability of non-compliance, perform detailed diagnostics and initiate treatment of concomitant diseases, carry out differential diagnosis of conditions mimicking asthma, educate the patient as to the inhalation technique and check it, eliminate unfavourable environmental factors, and modify current treatment. New treatment options for patients with asthma include: ultra-long-acting beta2-agonists, long-acting muscarine receptor antagonists (LAMA), monoclonal antibodies, and non-pharmacological interventions. The only LAMA approved for treatment of asthma is tiotropium bromide. The analyses performed demonstrated a high efficacy of tiotropium in terms of improved lung function parameters and prolonged time to the first asthma exacerbation. It is recommended as an add-on therapy at asthma treatment steps 4 and 5 according to GINA (Global Initiative for Asthma) 2014. The optimal asthma control is important from the medical as well as the economical point of view.
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Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Administração por Inalação , Asma/diagnóstico , Broncodilatadores/efeitos adversos , Broncodilatadores/uso terapêutico , Diagnóstico Diferencial , Custos de Cuidados de Saúde , Humanos , Cooperação do Paciente , Polônia , Brometo de Tiotrópio/administração & dosagemRESUMO
Three main monocyte subsets: classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++, differentially regulate tumor growth and survival. Thereby, in the present study we aimed to determine the role of distinct monocyte subsets in the prognostication of chronic lymphocytic leukemia (CLL). Moreover, we set out to analyze the effects of standard immune chemotherapy on different monocyte subsets and levels of membrane-associated and soluble forms of CD163, a monocyte/macrophage-related immunomodulatory protein. We demonstrated that the number of peripheral blood classical CD14++CD16- monocytes assessed at the time of diagnosis was negatively correlated with lymphocytosis and was decreased in the CLL patients who required immediate treatment as opposed to patients who qualified to 'watch and wait' strategy. Notably, lower baseline levels of classical CD14++CD16- monocytes in CLL patients who were qualified for 'watch and wait' therapy were associated with shorter time to initial treatment. Notably, therapy with rituximab, cyclophosphamide and fludarabine resulted in a significant reduction in the number of non-classical CD14+CD16++ monocytes and soluble form of CD163 but upregulation of membrane-associated monocyte CD163. Our data indicate that distinct monocyte subsets and two forms of CD163 are differentially modulated by both CLL and immune chemotherapy. Moreover, we proposed that quantification of classical monocytes at the time of diagnosis contributes to better prognostication of CLL patients.
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Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Receptores de Lipopolissacarídeos/sangue , Receptores de Superfície Celular/sangue , Receptores de IgG/sangue , Idoso , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Contagem de Células , Linhagem da Célula/genética , Ciclofosfamida/administração & dosagem , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/imunologia , Humanos , Fatores Imunológicos/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/imunologia , Receptores de Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/patologia , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Receptores de Superfície Celular/imunologia , Receptores de IgG/imunologia , Rituximab/administração & dosagem , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
INTRODUCTION: Recent studies in a mouse model of chronic lymphocytic leukemia (CLL) demonstrated that inhibition of the programmed death receptor 1 (PD1)-PDL1 axis resulted in correction of leukemiainduced CD8+ T cellrelated immune dysfunction and protected mice against CLL development. However, it remains unclear whether CLL development and progression can be also associated with CD4+ T cells expressing PD1. OBJECTIVES: We aimed to analyze whether a quantitative assessment of CD4+PD1+ T cells performed at the time of diagnosis can have prognostic significance in patients with CLL. PATIENTS AND METHODS: We examined 56 patients with newly diagnosed CLL at different stages of the disease. The quantitative assessment of PD1expressing CD4+ T cells was performed in all patients, using multicolor flow cytometry. RESULTS: We demonstrated that CLL patients with an advanced (high and intermediate risk) stage had a significantly higher number of CD4+PD1+ T cells compared with subjects with lowgrade disease. Importantly, we showed that the number of PD1expressing CD4+ T cells in the peripheral blood of patients referred for immediate treatment due to the advanced stage of the disease was significantly higher compared with subjects on watchful waiting. Finally, we found that treatmentnaive patients with higher numbers of CD4+PD1+ T cells at baseline showed a significantly shortened time to the first treatment compared with patients with a low number of CD4+PD1+ T cells. CONCLUSIONS: Our study showed that the quantative assessment of CD4+PD1+ T cells in peripheral blood using flow cytometry can facilitate prognostication of patients with newly diagnosed CLL.
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Linfócitos T CD4-Positivos/metabolismo , Expressão Gênica , Leucemia Linfocítica Crônica de Células B/metabolismo , Receptor de Morte Celular Programada 1/genética , Idoso , Linfócitos T CD4-Positivos/patologia , Progressão da Doença , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND/AIMS: One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. METHODS: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. RESULTS: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. CONCLUSION: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency.
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Inflamação/patologia , Ferro/metabolismo , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Biomarcadores/metabolismo , Contagem de Células Sanguíneas , Feminino , Humanos , Deficiências de Ferro , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Ferroproteínas não Heme/metabolismo , Estado NutricionalRESUMO
BACKGROUND: Previously, we demonstrated that glucocorticoid (GC) treatment of asthmatic patients resulted in decreasing frequencies of monocyte subsets expressing CD16 and capable of releasing TNF-α. Here, we wished to analyze whether the active form of vitamin D, i.e. vitamin D3, referred to as 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can exert GC-like proapoptotic effects on CD16-positive monocytes and thus decrease the proinflammatory potential of these cells. Finally, we set out to investigate whether the addition of 1,25-(OH)2D3 would facilitate the use of lower doses of GC without decreasing their anti-inflammatory properties. METHODS: Peripheral blood mononuclear cells collected from healthy individuals and asthmatic patients were cultured with 1,25-(OH)2D3 and/or varying doses of GC in the presence or absence of caspase inhibition. The cells were either directly stained for extracellular markers or prestimulated with lipopolysaccharide for the assessment of intracellular cytokine production and then analyzed by flow cytometry. RESULTS: We found that 1,25-(OH)2D3 alone (and in combination with GC) decreased the frequency of CD14++CD16+ and CD14+CD16++ monocytes from asthmatic patients and significantly diminished TNF-α production by the monocytes. With regard to the CD14+CD16++ subset, the monocyte-depleting effects of 1,25-(OH)2D3 were abrogated in the presence of pan-caspase inhibitor, suggesting a proapoptotic mechanism of 1,25-(OH)2D3 action. Interestingly, we found that a combined treatment of 1,25-(OH)2D3 and GC allowed for a 5-fold reduction of the GC dose while maintaining their anti-inflammatory effects. CONCLUSIONS: This study has revealed novel immunomodulatory properties of 1,25-(OH)2D3 directed against monocyte subsets capable of TNF-α production. In addition, our data suggest that the introduction of 1,25-(OH)2D3 to anti-inflammatory therapy would possibly allow for the use of lower doses of GC.
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Asma/tratamento farmacológico , Colecalciferol/uso terapêutico , Monócitos/imunologia , Receptores de IgG/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Anti-Inflamatórios/uso terapêutico , Asma/imunologia , Inibidores de Caspase/uso terapêutico , Feminino , Proteínas Ligadas por GPI/metabolismo , Glucocorticoides/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Monócitos/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
BACKGROUND: Juvenile idiopathic arthritis (JIA), similarly to other arthritides, can be associated with damage of endothelial layer of which structure and function is dependent on reparative properties of endothelial progenitor cells (EPC). To date, it remained unknown whether EPC numbers are altered in young JIA patients and whether on-going anti-inflammatory therapies could exert positive effects on these progenitor cells. METHODS: We performed a quantitative analysis of EPC numbers in 25 patients diagnosed with JIA according to International League of Associations for Rheumatism (ILAR) criteria [age 11.50 (7.50-15.00) years] in a broad context of inflammatory and cardiovascular parameters as well as different types of anti-inflammatory treatments. 11 healthy children [age 13.00 (11.00-14.00) years] were recruited as a control group. RESULTS: We demonstrated that EPC numbers were similar in JIA patients and control subjects (0.02% vs. 0.05%, respectively, p = 0.37). EPC levels in JIA patients were negatively correlated with index of insulin resistance (rho = -0.458, p = 0.021), endogenous insulin (rho = -0.472, p = 0.017), triglyceride (rho = -0.438, p = 0.029) and TNF-alpha levels (rho = -0.446, p = 0.026). Notably, glucocorticoid (GC) therapy, was associated with detection of decreased EPC levels in JIA patients (p = 0.023). In contrast, methothrexate (MTX) and etanercept therapy in JIA patients did not affect EPC levels (p = 0.92 and p = 0.08, respectively). CONCLUSIONS: We found that EPC numbers are maintained at normal levels in JIA patients and are not enhanced by disease-specific anti-inflammatory treatments.
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Anti-Inflamatórios/farmacologia , Artrite Juvenil/patologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/patologia , Adolescente , Antígenos CD34/metabolismo , Artrite Juvenil/sangue , Estudos de Casos e Controles , Contagem de Células , Criança , Estudos Transversais , Células Progenitoras Endoteliais/imunologia , Etanercepte , Feminino , Glucocorticoides/farmacologia , Humanos , Imunoglobulina G/farmacologia , Masculino , Metotrexato/farmacologia , Receptores do Fator de Necrose Tumoral , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
INTRODUCTION: Omalizumab is a monoclonal anti-immunoglobulin E antibody developed for the treatment of severe allergic asthma. The number of exacerbations used as a parameter of omalizumab therapy efficacy may be insufficient in many cases due to a relatively short time to first evaluation (16 weeks). Therefore, it is advisable to look for parameters of more prognostic value while continuing omalizumab therapy. AIM: To evaluate usefulness of analysis of changes of blood eosinophilia after 16 weeks of omalizumab therapy as a predictor of asthma exacerbations. MATERIAL AND METHODS: The study was conducted on a group of 13 patients with severe persistent allergic asthma treated with omalizumab. Blood eosinophil counts were measured before and after 16 weeks of anti-IgE therapy. On the basis of percentage of eosinophilia decrease (> 50% or < 50% of the initial value), patients were divided into two groups. Analysis of the asthma exacerbation rate during 12 months and time to first exacerbation was performed. RESULTS: In the group with a high decrease in blood eosinophil counts (group 1) we showed a statistically significantly lower asthma exacerbation rate in 12 months compared with the group with a low decrease in blood eosinophil counts (group 2) (p = 0.02). We also observed the tendency to longer time to first asthma exacerbation in group 1 compared to group 2 (p = 0.06). CONCLUSIONS: Our results showed that a decrease in blood eosinophilia during omalizumab therapy can be a predictor of asthma exacerbation. Evaluation of changes in blood eosinophil count should be taken into the consideration while estimating response to anti-IgE therapy in patients with severe allergic asthma.