RESUMO
PURPOSE: To assess whether preoperative C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), immunoglobulin E (IgE), and blood eosinophil percentage (EOS) can predict need for steroid irrigations after FESS. MATERIALS AND METHODS: Adult patients at BIDMC from inception until September 8, 2023 with chronic rhinosinusitis with nasal polyps who underwent FESS and had preoperative CRP (n = 129), ESR (n = 79), IgE (n = 107), or EOS (n = 125) were included. Labs were divided into normal (CRP: 0-5.0 mg/L; ESR: 0-15 mm/h; IgE: 150-300Ul/mL; EOS: 1-7 %) and high groups (CRP: >5.0 mg/L; ESR: >15 mm/h; IgE: >300Ul/mL; EOS: >7 %). The primary outcome was need for intranasal steroid irrigations after FESS (≤4 weeks, 4-12 weeks, 12-26 weeks, 26-52 weeks, 1-3 years, 3-5 years, and > 5 years). Receiver operating characteristic curves were created to determine thresholds for predicting postoperative steroid irrigations. RESULTS: Elevated IgE required intranasal steroid irrigation at 1-3 years (normal 34 %, high 62 %, p = 0.02), 3-5 years (normal 24 %, high 48 %, p = 0.04), and > 5 years (normal 19 %, high 43 %, p = 0.02). Elevated EOS required intranasal steroid irrigation at 26-52 weeks (normal 7 %, high 25 %, p = 0.009) and > 5 years (normal 19 %, high 46 %, p = 0.005). The area under the curve for IgE at 1-3 years was 0.696 (95 % CI: 0.597-0.795) with cutoff at 144-148 Ul/mL. CRP and ESR were not predictive of postoperative intranasal steroid treatment. CONCLUSIONS: Elevated IgE and EOS (but not CRP or ESR) may predict need for intranasal steroid treatment after FESS.
Assuntos
Sedimentação Sanguínea , Proteína C-Reativa , Imunoglobulina E , Pólipos Nasais , Rinite , Sinusite , Humanos , Sinusite/cirurgia , Pólipos Nasais/cirurgia , Pólipos Nasais/sangue , Rinite/cirurgia , Rinite/sangue , Doença Crônica , Masculino , Feminino , Pessoa de Meia-Idade , Imunoglobulina E/sangue , Adulto , Proteína C-Reativa/análise , Eosinófilos , Esteroides/administração & dosagem , Valor Preditivo dos Testes , Lavagem Nasal/métodos , Endoscopia/métodos , Período Pré-Operatório , Cuidados Pré-Operatórios/métodos , Irrigação Terapêutica/métodos , Idoso , RinossinusiteRESUMO
BACKGROUND: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. OBJECTIVE: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). METHODS: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. RESULTS: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. CONCLUSION: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.
Assuntos
Asma , Biomarcadores , Vesículas Extracelulares , Galectinas , Sinusite , Humanos , Asma/sangue , Asma/fisiopatologia , Asma/imunologia , Asma/diagnóstico , Vesículas Extracelulares/metabolismo , Feminino , Masculino , Galectinas/sangue , Biomarcadores/sangue , Adulto , Pessoa de Meia-Idade , Sinusite/sangue , Sinusite/imunologia , Rinite/sangue , Rinite/imunologia , Rinite/fisiopatologia , Pólipos Nasais/imunologia , Pólipos Nasais/sangue , Eosinófilos/imunologia , Idoso , Doença CrônicaRESUMO
The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) defines markers for type2 inflammation in the context of indicating biological therapy in severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) as either a total serum immunoglobulin E (total-IgE) <100 kU/L, a blood eosinophil count (BEC, expressed as -109 cells / L) >=0.25, or a tissue eosinophil count >=10 per high power field (HPF) (1). Recently, an EPOS/EUFOREA expert panel advised to lower the threshold for BEC from >=0.25 (EPOS2020) to >=0.15 (EUFOREA2023) to align with thresholds used for biological indication in asthma patients (2). As far as we know, there is no literature supporting the cut-off value for total-IgE.
Assuntos
Biomarcadores , Eosinófilos , Pólipos Nasais , Rinite , Sinusite , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/terapia , Sinusite/complicações , Sinusite/sangue , Sinusite/terapia , Rinite/complicações , Rinite/sangue , Doença Crônica , Biomarcadores/sangue , Biomarcadores/análise , Imunoglobulina E/sangue , Contagem de Leucócitos , RinossinusiteRESUMO
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by tissue heterogeneity and high postoperative recurrence risk. This study aims to employ cytokine analyses to identify serum biomarkers associated with postoperative CRSwNP recurrence and elucidate underlying recurrent mechanisms. METHODS: A prospective cohort study was conducted on CRSwNP patients undergoing functional endoscopic sinus surgery. Serum and tissue samples were collected and analyzed for multiple cytokines. Participants were followed for 3 years and categorized into recurrent and non-recurrent groups. Cytokine profiles were compared, and potential markers for recurrence were further assessed. Macrophage migration inhibitory factor (MIF) expression in macrophages was modulated, and their polarization and cytokine secretion were assessed. RESULTS: In the discovery cohort (21 recurrent and 40 non-recurrent patients), circulating cytokine profiles differed significantly, with 8 cytokines showing differential expression between the two groups. Among them, serum eotaxin, MIF, RANTES, and TRAIL exhibited promise in predicting recurrence. In the validation cohort (24 recurrent and 44 non-recurrent patients), serum eotaxin, MIF, and TRAIL levels were higher in recurrent cases. Tissue MIF was elevated in recurrent cases and had a strong predictive value for recurrence. Moreover, tissue MIF was co-expressed with CD206 in recurrent cases. Mechanistically, MIF overexpression promoted macrophage M2 polarization and TGF-ß, CCL-24, and MIF secretion, and MIF recombinant protein facilitated M2 polarization, and TGF-ß1 and CCL-24 production, contributing to CRSwNP recurrence. CONCLUSIONS: Serum-specific cytokine signatures were associated with postoperative recurrence risk in CRSwNP. Elevated MIF enhanced macrophage M2 polarization and cytokine secretion, contributing to the recurrent mechanisms of CRSwNP.
Assuntos
Citocinas , Fatores Inibidores da Migração de Macrófagos , Macrófagos , Pólipos Nasais , Recidiva , Rinite , Sinusite , Humanos , Pólipos Nasais/cirurgia , Pólipos Nasais/metabolismo , Pólipos Nasais/imunologia , Pólipos Nasais/complicações , Fatores Inibidores da Migração de Macrófagos/sangue , Fatores Inibidores da Migração de Macrófagos/metabolismo , Sinusite/cirurgia , Sinusite/metabolismo , Sinusite/sangue , Sinusite/imunologia , Rinite/cirurgia , Rinite/metabolismo , Rinite/sangue , Rinite/imunologia , Doença Crônica , Estudos Prospectivos , Masculino , Citocinas/metabolismo , Citocinas/sangue , Feminino , Macrófagos/metabolismo , Pessoa de Meia-Idade , Adulto , Oxirredutases Intramoleculares/sangue , Oxirredutases Intramoleculares/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , RinossinusiteRESUMO
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease with high heterogeneity and postoperative recidivation. The IL-33/ST2 axis is known to be involved in Th2 immune responses. This study is aimed at exploring levels of serum IL-33 and soluble ST2 (sST2) in CRSwNP patients and their potential for predicting CRSwNP endotypes and postoperative recurrence. Methods: The present study recruited 149 CRSwNP patients, 80 of whom were noneosinophilic (neCRSwNP) and 69 eosinophilic (eCRSwNP), as well as 60 healthy controls (HCs). Serum samples were collected from all participants, and sST2 and IL-33 concentrations were measured using ELISA. Multivariate analysis, receiver operating characteristic (ROC) curves, and Kaplan-Meier curves were used to evaluate the value of serum sST2 and IL-33 levels in distinguishing CRSwNP endotypes and predicting postoperative recurrence. Results: The levels of serum sST2 and IL-33 in CRSwNP patients were significantly higher than those in HCs, especially in the eCRSwNP group. Increased sST2 and IL-33 levels were associated with eosinophil counts and percentages in both tissue and blood. Multivariate regression and ROC curve analysis showed that serum sST2 and IL-33 exhibited potential for distinguishing CRSwNP endotypes, and the combination of serum IL-33 and sST2 showed even more predictive power. Finally, 124 CRSwNP patients completed the entire 3-year follow-up. Multivariate analysis and Kaplan-Meier curves showed that serum sST2 and IL-33 levels were associated with recurrence; serum sST2 and IL-33 each exhibited potential for predicting postoperative recurrence, and combining serum sST2 and IL-33 exhibited better accuracy and practicability. Conclusion: Our results suggested that serum sST2 and IL-33 levels were upregulated in CRSwNP patients and related to the degree of mucosal eosinophil infiltration and postoperative recurrence. Serum sST2 and IL-33 might serve as objective biomarkers for distinguishing phenotypes and predicting recurrence in CRSwNP, and their combined use outperformed either marker alone.
Assuntos
Interleucina-33 , Pólipos Nasais , Rinite , Sinusite , Biomarcadores/sangue , Doença Crônica , Eosinófilos/patologia , Humanos , Interleucina-33/sangue , Pólipos Nasais/sangue , Rinite/sangue , Rinite/cirurgia , Sinusite/sangue , Sinusite/cirurgiaRESUMO
BACKGROUND: B cell-activating factor (BAFF) is a proinflammatory cytokine involved in inflammatory and allergic diseases, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study aims to explore the predictive value of circulating BAFF in CRSwNP endotypes and postoperative recurrence. METHODS: We recruited 120 CRSwNP patients, including 68 non-eosinophilic CRSwNP (neCRSwNP) patients, 52 eosinophilic CRSwNP (CRSwNP) patients, and 60 healthy controls (HCs). Circulating BAFF levels of all participants were measured by enzyme-linked immunosorbent assay (ELISA), and receiver-operating characteristic (ROC) and logistic regression analyses were applied to assess the predictive ability of BAFF levels in distinguishing CRSwNP endotypes. All CRSwNP patients were followed for more than 3 years, and the predictive value of circulating BAFF for postoperative recurrence was evaluated. RESULTS: Serum BAFF levels were elevated in CRSwNP patients compared with the HCs (P < 0.01) and significantly higher in eCRSwNP patients. The increased serum BAFF concentrations positively correlated with blood eosinophil counts and percentages, tissue eosinophil counts, and serum total IgE (P < 0.05). The ROC curve showed that serum BAFF exhibited strong discriminative ability for eCRSwNP. Finally, 99 CRSwNP patients completed the follow-up schedule, 65 patients were classified into non-recurrence group and the other 34 patients were categorized into recurrence group. Serum BAFF levels were significantly higher in recurrence group than non-recurrence group (P < 0.001), and the ROC curve suggested a high predictive value of serum BAFF in predicting postoperative recurrence. Moreover, logistic regression and Kaplan-Meier curves showed that serum BAFF was an independent risk factor for postoperative recurrence (P < 0.05). CONCLUSION: Our data suggested that serum BAFF levels were upregulated in CRSwNP patients and correlated with mucosal eosinophil infiltration severity. Serum BAFF seemed to be a novel biomarker for preoperatively distinguishing CRSwNP endotypes and predicting postoperative recurrence.
Assuntos
Fator Ativador de Células B/sangue , Eosinofilia/sangue , Pólipos Nasais/sangue , Rinite/sangue , Sinusite/sangue , Adulto , Biomarcadores/sangue , Doença Crônica , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Nasais , Período Pós-Operatório , RecidivaRESUMO
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease and can be categorized into eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP). Exploring effective biomarkers to distinguish endotypes is important for personalized therapies. The present study aims to evaluate the predictive value of serum MIF in CRSwNP endotypes. METHODS: One hundred and twenty CRSwNP patients, including 51 eCRSwNP and 69 neCRSwNP, 40 chronic rhinosinusitis without nasal polyps (CRSsNP) patients and 40 healthy controls (HC) were enrolled. Serum MIF levels were determined by enzyme-linked immunosorbent assay (ELISA). The patients' clinical variables were analyzed for correlations with serum MIF. Receiver operating characteristic (ROC) curve and multivariate analysis were utilized to assess the predictive value of serum MIF in CRSwNP endotypes. RESULTS: The serum MIF levels were significantly higher in CRSwNP group than CRSsNP group and HC group (P < 0.001), and the serum MIF levels were increased in eCRSwNP compared to neCRSwNP group (P = 0.006). Elevated serum MIF levels were significantly correlated with blood eosinophil (B-EOS) count (r = 0.411, P < 0.001), B-EOS percentage (r = 0.377, P < 0.001), visual analog scale score (r = 0.204, P = 0.025), tissue eosinophil (T-EOS) count (r = 0.705, P < 0.001) and T-EOS percentage (r = 0.671, P < 0.001) in CRSwNP patients. ROC curve demonstrated that serum MIF exhibited good preoperative prediction in CRSwNP endotypes (area under the curve = 0.925, P < 0.001). Multivariate regression analysis showed that serum MIF was an independent factor associated with CRSwNP endotypes. CONCLUSIONS: This was the first study identifying serum MIF as a possible specific biomarker for preoperatively distinguishing CRSwNP endotypes. Furthermore, the serum MIF levels were found to be closely associated with the degree of mucosal eosinophil infiltration.
Assuntos
Ensaio de Imunoadsorção Enzimática , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Pólipos Nasais/sangue , Rinite/sangue , Sinusite/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiotaxia de Leucócito , Doença Crônica , Eosinófilos/imunologia , Eosinófilos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Pólipos Nasais/diagnóstico , Pólipos Nasais/imunologia , Valor Preditivo dos Testes , Rinite/diagnóstico , Rinite/imunologia , Sinusite/diagnóstico , Sinusite/imunologia , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND: CD48 is a costimulatory receptor of the immune response. Interactions between CD48 and CD244 (2B4) on mast cells and eosinophils suggest that these cells can act synergistically in the 'allergic effector unit' to promote inflammation. This report explores the role of CD48 in persistent allergic (PAR) and non-allergic rhinitis (NAR). METHODS: In this study, serum was obtained from 70 subjects (45 female, 64%; mean age, 36; range 18-70 years) to estimate the levels of sCD48 and two eosinophils-related parameters, ECP and eotaxin-1/CCL11. Twenty patients with PAR, 15 patients with NAR, and 35 healthy controls were included. The intensity of rhinitis symptoms was estimated by the Total Nasal Symptom Score. We also assessed the fractional exhaled nitric oxide bronchial and nasal fractions (FeNO) and neutrophil to lymphocyte (NLR) and eosinophil to lymphocyte (ELR) ratios. RESULTS: Significantly higher sCD48 serum levels were observed in the NAR group than in the PAR and control groups, and significant correlations were found between the serum level of sCD48 and the number and percentage of eosinophils. ECP and eotaxin-1/CCL11 serum levels were also found to be significantly higher in the NAR group. CONCLUSIONS: CD48 may be involved in eosinophilic pathophysiological reactions in non-allergic rhinitis.
Assuntos
Antígeno CD48/sangue , Rinite/sangue , Rinite/diagnóstico , Adolescente , Adulto , Idoso , Animais , Antígeno CD48/imunologia , Estudos de Casos e Controles , Eosinófilos/imunologia , Eosinófilos/metabolismo , Feminino , Humanos , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Pessoa de Meia-Idade , Projetos Piloto , Pyroglyphidae/imunologia , Pyroglyphidae/metabolismo , Rinite/imunologia , Rinite Alérgica/sangue , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Testes Cutâneos/métodos , Adulto JovemRESUMO
The mechanisms that lead to disease onset and propagation in patients with chronic rhinosinusitis (CRS) are not fully elucidated. Maresins (MaR) are a family of essential fatty acid-derived lipid mediators that play a central role in the regulation of inflammation with several studies demonstrating that these mediators display protective activities in airway inflammation. Therefore, in the present studies we evaluated whether concentrations of these mediators were altered in both peripheral blood and nasal secretions from CRS patients. Herein, we focused on patients with CRS that also develop nasal polyps (CRSwNP), given that therapeutic options for the treatment of these patients are limited. Thereby, insights into disease mechanisms in these patients may help design more effective treatments. For this purpose, we compared maresin concentrations from CRSwNP patients with those found in healthy volunteers or patients with an upper respiratory tract infection (URTI), as a self-resolving inflammatory condition. Using liquid chromatography tandem mass spectrometry, we found that MaR concentrations were significantly decreased in plasma from patients with CRSwNP when compared to healthy volunteers. MaR concentrations were observed to be significantly upregulated in nasal secretions from patients with CRSwNP when compared with both healthy volunteers and URTI subjects. Concentration of these mediators in both plasma and nasal secretions from CRSwNP patients were positively correlated with quality-of-life scores in these patients. Assessment of the concentrations of other pro-resolving and pro-inflammatory lipid mediators (LM) demonstrated that there was a general shift in LM levels in both plasma and nasal secretions from CRSwNP when compared with healthy volunteers and URTI subjects. Of note, incubation of peripheral blood cells from CRSwNP patients with MaR1 downregulated the expression of activation markers on peripheral blood phagocytes, including CD41 and CD62P, markers of platelet-leukocyte heterotypic aggregates. Together these findings demonstrate that both local and systemic LM concentrations, in particularly those of the MaR family, become altered in patients with CRSwNP. They also suggest that therapeutics designed around MaR1 may be useful in regulating the activation of phagocytes in patients with CRSwNP thereby potentially also limiting the local inflammatory response in these patients.
Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Mucosa Nasal/metabolismo , Pólipos Nasais/sangue , Rinite/sangue , Sinusite/sangue , Adulto , Estudos de Casos e Controles , Cromatografia Líquida , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/diagnóstico , Rinite/diagnóstico , Via Secretória , Sinusite/diagnóstico , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Immunoglobulin E (IgE) is the most important promoter of allergic inflammation. However, there are few systematic studies on IgE in age range, genders, disease spectrum, and time regularity. AIM: To screen the common allergens, allergen spectrum, and IgE difference between type 2 inflammatory allergic diseases and other allergic diseases in Weifang, China. METHODS: A retrospective study was performed by estimating patients' clinical data suffering from allergic diseases (urticaria, pollinosis, allergic rhinitis, atopic dermatitis, and bronchial asthma) between May 2019 and April 2020 using an allergen detection kit of Macro-Union Pharmaceutical. RESULTS: 732 of the 1367 patients showed different antigen positive, and the positive rate was 53.5%. The most common allergens were dust mites, mixed fungi, Artemisia pollen, cat/dog dander, and cockroaches. There were 27.0% (369/1367) of the patients with single positive allergen-specific IgE (sIgE), 26.5% (363/1367) with multiple-positive IgE. The total immunoglobulin E (tIgE) levels varied with gender, age, and type of disease. There was a difference in the distribution of allergens between children and adults. A positive correlation between the serum-specific IgE and the corresponding local inhaled allergen density was observed. CONCLUSIONS: In this study, we found that type 2 inflammatory allergic diseases have higher serum IgE and a higher probability of inhaled sIgE positive. According to age, gender, and condition, serological IgE detection of allergens provides new insight into the early diagnosis and prevention of allergic diseases.
Assuntos
Asma/sangue , Dermatite/sangue , Hipersensibilidade/sangue , Imunoglobulina E/sangue , Rinite/sangue , Adolescente , Adulto , Idoso , Alérgenos/sangue , Asma/imunologia , Criança , Pré-Escolar , China/epidemiologia , Dermatite/imunologia , Feminino , Humanos , Hipersensibilidade/imunologia , Lactente , Recém-Nascido , Inflamação , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Rinite/imunologia , Adulto JovemRESUMO
Chemotherapy is generally effective for extranodal natural killer (NK)/T-cell lymphoma (ENKTCL), nasal type. Nevertheless, multidrug resistance (MDR) remains a key challenge in treating nasal NK/T-cell lymphoma. Interleukin-6 (IL-6) is reportedly an important regulator of MDR in many cancers, implicating a role of IL-6 in the chemotherapy response. However, the effects and mechanism of IL-6 in nasal NK/T-cell lymphoma remain unclear. Herein, we demonstrated that the IL-6 serum level was decreased in nasal NK/T-cell lymphoma patients compared to chronic rhinitis patients. Lower serum levels of IL-6 were closely correlated with Ki67 expression and patient survival. ATP-binding cassette (ABC) drug transporter ABCC4 in patients was abnormally upregulated. IL-6 significantly inhibited resistance to Adriamycin (ADM) in ADM-resistant SNK-6 cells (SNK-6/ADM). Moreover, IL-6 resulted in cell cycle arrest and led to apoptosis in SNK-6/ADM cells. Furthermore, IL-6 decreased ABCC4, p-JAK2, p-STAT3, and phospho-NF-κB p65 expression in SNK-6/ADM cells. IL-6 in combination with ADM inhibited tumor growth and increased the survival of SNK-6/ADM xenograft mice. In conclusion, our findings suggest that IL-6 can inhibit the upregulation of ABCC4 and inactivate the JAK2/STAT3/NF-κB/P65 pathway to sensitize NK/T-cell lymphoma to ADM, indicating that combination therapy with IL-6 and other chemotherapeutic drugs may be effective in reversing acquired resistance in nasal NK/T-cell lymphoma.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Interleucina-6/uso terapêutico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doença Crônica , Regulação para Baixo/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Interleucina-6/sangue , Interleucina-6/farmacologia , Janus Quinase 2/metabolismo , Linfoma Extranodal de Células T-NK/sangue , Linfoma Extranodal de Células T-NK/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Rinite/sangue , Rinite/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismoRESUMO
BACKGROUND: The prevalence of eosinophilic CRSwNP in China has increased significantly over the last 20 years, noninvasive methods that could assist in diagnosis are urgently needed. AIMS: The aim of this study is to explore the clinical significance of peripheral blood eosinophil in diagnosing ECRS. MATERIALS AND METHODS: We conducted a prospective study of 221 patients diagnosed with CRS. Lund-Mackay score, peripheral blood eosinophil absolute count, peripheral blood eosinophil percentage were detection to compare the clinical features with ECRS and non-ECRS. ROC curve was performed to assess the efficiency of clinical index to predict ECRS. RESULTS: The ECRS group of patients had significantly higher scores compared with those of the non-ECRS group. Different extent and severity of mucosal thickening on total Lund-Mackay scores, anterior ethmoidal, posterior ethmoidal and ostiomeatal complex have confirmed different blood eosinophil levels in CRS patients. The combination of peripheral blood eosinophil percentage and posterior ethmoidal score to predict ECRS was 0.807. CONCLUSIONS AND SIGNIFICANCE: The increase in peripheral blood eosinophil percent indicates the deterioration the inflammation of chronic rhinosinusitis and the level of posterior ethmoidal score and peripheral blood eosinophil percentage have a positive predictive value regarding ECRS identification.
Assuntos
Eosinofilia/complicações , Eosinófilos , Rinite/complicações , Sinusite/complicações , Adulto , China , Doença Crônica , Eosinofilia/sangue , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Rinite/sangue , Rinite/imunologia , Sinusite/sangue , Sinusite/imunologiaRESUMO
The immune pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains obscure. Our aim was to compare humoral immunity and white blood cell counts in patients with CRSwNP and controls. A prospective case-control study was carried out in 37 patients with CRSwNP and 34 controls without CRS. Clinical data were gathered through a systematic interview. Computed tomography scan, skin prick test, spirometry, and immunological parameters (leukocyte differential count, immunoglobulin classes, and immunoglobulin [Ig] G subclasses) in serum specimens were obtained. Statistical analysis was performed using SPSS v.23. The prevalence of chronic lower respiratory diseases was greater in the CRSwNP group (P < .001), but atopic disease had no significant difference. A significantly higher eosinophil (P < .001) and basophil relative count (P = .022) and a lower relative neutrophil count (P = .013) were found among CRSwNP group. Patients with CRSwNP had higher IgG1 (P = .022), but lower IgG2 (P = .014) and IgG3 (P = .018) serum levels compared to controls; IgG4, total IgG, IgA, IgM, and IgE serum levels did not differ between groups, as well as the prevalence of immunoglobulin classes or IgG subclasses deficiency. The variation observed in peripheral relative leukocyte count and the systemic IgG1 subclass shift are similar to what is known to happen in nasal polyp tissue. A unique systemic immune profile seems to be present in patients with CRSwNP.
Assuntos
Imunidade Humoral/imunologia , Isotipos de Imunoglobulinas/sangue , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/sangue , Estudos Prospectivos , Rinite/sangue , Sinusite/sangue , Testes CutâneosRESUMO
We examined the appearance of serum anti-phage antibodies in 25 patients with chronic sinusitis treated with phage therapy (PT). Approximately 30% of patients with weak antibody responses responded positively to PT, which was similar to the results of treatment achieved in a group of patients with high antibody production. In addition, there was no correlation between antibody level and the outcome of PT. These data, derived from a homogenous group of patients, confirm our earlier findings suggesting that the prognostic significance of serum anti-phage antibodies for the outcome of PT should be determined by relevant clinical trials.
Assuntos
Anticorpos Antivirais/sangue , Bacteriófagos/imunologia , Terapia por Fagos , Doença Crônica , Humanos , Testes de Neutralização , Rinite/sangue , Rinite/terapia , Sinusite/sangue , Sinusite/terapia , Resultado do TratamentoAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Antiasmáticos/uso terapêutico , Asma/sangue , Asma/diagnóstico por imagem , Asma/imunologia , Doença Crônica , Resistência a Medicamentos , Eosinofilia/sangue , Eosinofilia/diagnóstico por imagem , Eosinofilia/imunologia , Eosinófilos/imunologia , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/imunologia , Rinite/sangue , Rinite/diagnóstico por imagem , Rinite/imunologia , Sinusite/sangue , Sinusite/diagnóstico por imagem , Sinusite/imunologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: Urine leukotriene E4 (uLTE4) is a biomarker of leukotriene synthesis and is elevated in patients with aspirin-exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin-tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP. METHODS: A retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund-Mackay CT score, spirometry and lab values) were collected. RESULTS: Among the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P < .001), aspirin sensitivity (P < .001), worse Lund-Mackay CT scores (P = .002) and other objective markers of disease severity including serum IgE (P = .05), presenting blood eosinophil level (P < .001), and the highest recorded eosinophil level (P < .001). In subgroup analysis, associations of uLTE4 to disease markers had stronger correlations in the aspirin sensitive CRSwNP group (R range 0.31-0.52) than the aspirin tolerant CRSwNP group (R range -0.30-0.24). uLTE4 levels were not associated with subjective symptom scores (SNOT22 and ACT scores). CONCLUSION: Elevated uLTE4 biomarker levels are associated with worsened objective markers of disease severity in CRSwNP patients but not patient-reported symptom measures. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:961-966, 2021.
Assuntos
Leucotrieno E4/urina , Pólipos Nasais/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Doença Crônica , Eosinófilos , Feminino , Humanos , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/sangue , Pólipos Nasais/imunologia , Pólipos Nasais/urina , Seios Paranasais/diagnóstico por imagem , Estudos Retrospectivos , Rinite/sangue , Rinite/imunologia , Rinite/urina , Índice de Gravidade de Doença , Teste de Desfecho Sinonasal , Sinusite/sangue , Sinusite/imunologia , Sinusite/urina , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES/HYPOTHESIS: Chronic rhinosinusitis (CRS) is a heterogenic disease with different inflammatory patterns depending on the presence (CRSwNP) or absence (CRSsNP) of polyps and geographical location. A shift toward type 2 endotype has been seen in Asia. We aim to investigate whether there has been type 2 shift in Belgium and to further endotype CRS based on clinical markers. STUDY DESIGN: Prospective descriptive study. METHODS: Four hundred and thirty eight patients with CRS undergoing sinus surgery at Ghent University Hospital between 2007 and 2018 were included and stratified based on phenotype, comorbidities, inflammatory markers in tissue, and two different time points of surgery. Tissue samples from surgery were analyzed for type 2 markers. In a subgroup of CRSwNP blood eosinophils (EBC) was available. RESULTS: There was an increase in type 2 inflammatory markers in the latter group versus the earlier, in non-asthmatic, non-allergic CRS patients regardless of phenotype. The proportion of IL-5+ patients was elevated in the latter group in CRSwNP. Inflammatory markers and comorbidities differ between IL-5+ CRSsNP and CRSwNP subjects, no difference was seen in IL-5- CRS. EBC can together with information on comorbidities help identify type 2 CRSwNP in a clinical setting. CONCLUSION: There is a shift toward type 2 inflammation within the CRS population over recent 8 years also in Belgium. This shift implies that we expect to see more cases of severe and difficult to treat CRS in the future. Polyp formation is not directly linked to the presence or concentrations of type 2 inflammatory markers. Clinical parameters and EBC > 300 cells/µL can be used to identify type 2 CRSwNP. LEVEL OF EVIDENCE: 3. Laryngoscope, 131:E1408-E1414, 2021.
Assuntos
Eosinófilos/imunologia , Interleucina-5/sangue , Pólipos Nasais/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica , Biomarcadores/sangue , Doença Crônica , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Inflamação/cirurgia , Interleucina-5/imunologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Mucosa Nasal/patologia , Mucosa Nasal/cirurgia , Pólipos Nasais/sangue , Pólipos Nasais/imunologia , Pólipos Nasais/cirurgia , Estudos Prospectivos , Rinite/sangue , Rinite/imunologia , Rinite/cirurgia , Índice de Gravidade de Doença , Sinusite/sangue , Sinusite/imunologia , Sinusite/cirurgia , Adulto JovemRESUMO
BACKGROUND: Chronic rhinosinusitis may be associated with nasal polyposis. Recurrence of disease is often observed and may be due to an intolerance of acetylsalicylic acid. Sex hormones are known to modulate allergic reactions and inflammation. Whether they may be involved in the development and progression of nasal polyposis has not been investigated yet. AIM: Examine the relationship between levels of sex hormones and nasal polyposis. METHODS: Hormonal levels (estradiol, testosterone and progesterone) in patients with nasal polyposis (n = 26) with or without acetylsalicylic acid-intolerance were determined and compared to hormonal levels in patients with septal deviation (n = 35). Cone-beam computed tomography scans were analysed by using scores as defined by Lund and Mackay and by Kennedy. RESULTS: Our results show a 5 times greater odds (p = 0.01) for developing nasal polyposis in the presence of lowered estradiol plasma levels than in the presence of normal / elevated levels. When analyzing females and males separately, a 6 times greater odds for females to develop nasal polyposis in the presence of lowered estradiol plasma levels was calculated (p = 0.02). Thus, females are more likely to develop nasal polyposis when they have lowered estradiol levels than males. In addition, female patients showed an increased risk for developing ASA intolerance (p = 0.01). CONCLUSION: Variation of sex hormones may be involved in nasal polyposis. Further studies including more patients to validate the presented results are required. SIGNIFICANCE: Retrospective clinical investigation suggesting a correlation between varying sex hormones and nasal polyposis.
Assuntos
Aspirina/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Estradiol/sangue , Pólipos Nasais/imunologia , Progesterona/sangue , Testosterona/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Tomografia Computadorizada de Feixe Cônico , Hipersensibilidade a Drogas/sangue , Hipersensibilidade a Drogas/imunologia , Estradiol/imunologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/diagnóstico por imagem , Pólipos Nasais/sangue , Pólipos Nasais/diagnóstico , Progesterona/imunologia , Recidiva , Estudos Retrospectivos , Rinite/sangue , Rinite/induzido quimicamente , Rinite/epidemiologia , Rinite/imunologia , Sinusite/sangue , Sinusite/induzido quimicamente , Sinusite/epidemiologia , Sinusite/imunologia , Testosterona/imunologia , Adulto JovemRESUMO
INTRODUCTION: Studies have shown that calprotectin has a strong pro-inflammatory effect. Elevated calprotectin levels in the serum can be used as a strong clinical marker indicating the presence of inflammation. OBJECTIVE: To investigate serum calprotectin levels in patients with chronic rhinosinusitis (CRS) and to determine the applicability of calprotectin as a potential molecular pro-inflammatory biomarker for CRS. METHODS: The study consisted of three groups: chronic rhinosinusitis with polyps (CRSwNP group), chronic rhinosinusitis without polyps (CRSwoNP), and healthy control. CRS patients with polyps were further divided into two groups depending on the presence/absence of Samter's triad. The Nose Obstruction Symptom Evaluation (NOSE) scale score and serum calprotectin value were evaluated in all participants. RESULTS: The mean serum calprotectin value was 79.5±11.8 ng/ml for the CRSwNP group, 71.3±16 ng/ml for the CRSwoNP group, and 61.9±11.6 ng/ml for the control group (p<0.001). The Samter's triad group had a significantly higher calprotectin value than the non-Samter's triad group (p=0.03). There was a significant correlation between the NOSE scores and calprotectin levels (rho=0.734, p<0.001). CONCLUSION: Serum calprotectin values were correlated with the severity of symptoms in patients with CRS; thus, it seems to be a valuable pro-inflammatory biomarker for the diagnosis of the disease and determining its severity. Further studies with larger series are needed to evaluate the preoperative and postoperative serum calprotectin values ââin patients undergoing surgery.
Assuntos
Asma Induzida por Aspirina/sangue , Asma Induzida por Aspirina/complicações , Complexo Antígeno L1 Leucocitário/sangue , Pólipos Nasais/sangue , Pólipos Nasais/complicações , Rinite/sangue , Rinite/complicações , Índice de Gravidade de Doença , Sinusite/sangue , Sinusite/complicações , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Type 2 inflammation and eosinophilic infiltration are prominent pathologic features of chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of the present study was to determine the roles of Tregs in controlling type 2 inflammation and inhibiting eosinophilic infiltration in CRSwNP. A total of 134 nasal polyps, 67 ostiomeatal complex from chronic rhinosinusitis (CRS) and 62 normal nasal tissues from controls were collected to study the enumeration and function of Tregs cells and the expressions of cytokine profiles via immunofluorescence staining, flow cytometry, qRT-PCR, ELISA, and/or H&E staining. The effects of Tregs on type2 and type3 inflammations were determined in an eosinophilic chronic sinusitis (ECRS) mice model. It was confirmed that the CRSwNP displayed the features of Th2 and Th17 cells-mediated inflammation, accompanying by an increased level of eosinophilic infiltration and the eosinophil cationic protein (ECP), with a decreased frequency of Treg cells. Furthermore, the percentages of CD4+CD25+CD127lowTreg and CD4+CD25+Foxp3+Treg were only decreased in the polyps of CRSwNP but not in the paired peripheral blood. The CRSwNP possessed the decreased Nrp1+Tregs, Helios+Treg, and low TGF-ß and interleukin (IL)-10 expressions in Tregs. The ECRS mice showed similar inflammatory characteristics to CRSwNP patients. The adoptive transfer of CD4+CD25+Foxp3+ Treg cells significantly decreased the inflammatory cytokines, eosinophilic chemotactic factors in the mucosa of the ECRS mice without alteration of the immune balance in the peripheral blood and spleen. In conclusion, CRSwNP showed high type 2 and type3 inflammation and defective Tregs. The induced regulatory T cell (iTreg) may correct the imbalance between immune tolerance and effect via limiting the eosinophil recruitment of mucosa in CRSwNP.