Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology.

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.

Preoperative laboratory measurements as a predictor for nasal steroid irrigations after sinus surgery for chronic rhinosinusitis with nasal polyps.

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.

Eosinophils are the dominant type2 marker for the current indication of biological treatment in severe uncontrolled chronic rhinosinusitis with nasal polyps.

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.

Elevated MIF identified by multiple cytokine analyses facilitates macrophage M2 polarization contributing to postoperative recurrence in chronic rhinosinusitis with nasal polyps.

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.

Burnt sugarcane harvesting is associated with rhinitis symptoms and inflammatory markers / Colheita de cana-de-açúcar queimada está associada a sintomas de rinite e marcadores inflamatórios

Abstract Introduction: Burnt sugarcane harvesting requires intense physical exertion in an environment of high temperature and exposure to particulate matter. Objective: To evaluate the effects of burnt sugarcane harvesting on rhinitis symptoms and inflammatory markers in sugarcane workers. Methods: A total of 32 male sugarcane workers were evaluated with questionnaire for rhinitis symptoms, and for inflammatory markers on peripheral blood and nasal lavage, in the non-harvesting, and 3 and 6 months into the sugarcane harvesting period. Weather data and particulate matter fine concentrations were measured in the same day. Results: The particulate matter concentrations in sugarcane harvesting were 27 (23-33 µg/m3), 112 (96-122 µg/m3), and 63 (17-263 µg/m3); 24 h temperatures were 32.6 (25.4-37.4 ºC), 32.3 (26.7-36.7 ºC) and 29.7 (24.1-34.0 ºC) and relative humidities were 45.4 (35.0-59.7%), 47.9 (39.1-63.0%), and 59.9 (34.7-63.2%) in the non-harvesting period, three and 6 months of the harvesting period. The age was 37.4 ± 10.9 years. The prevalence of rhinitis symptoms was significantly higher at 3 months of the harvesting period (53.4%), compared to non-harvesting period (26.7%; p = 0.039) and at 6 months into the harvesting period (20%; p = 0.006). Concentrations of interleukin 6 (IL-6) in nasal lavage increased after 3 months of the harvesting period compared to the non-harvesting period (p = 0.012). The presence of rhinitis symptoms, after 3 months of the harvesting period, was directly associated with blood eosinophils and inversely associated with neutrophils. Conclusions: After 3 months of work in burnt sugarcane harvesting the prevalence of rhinitis symptoms and IL-6 in nasal lavage increased. Furthermore, eosinophil counts were directly associated with the rhinitis symptoms in the period of higher concentration of particulate matter.

Resumo Introdução: A colheita de cana-de-açúcar queimada requer esforço físico intenso em um ambiente com altas temperaturas e exposição a material particulado. Objetivo: Avaliar os efeitos da colheita de cana-de-açúcar queimada nos sintomas de rinite e marcadores inflamatórios de cortadores de cana-de-açúcar. Método: Foram avaliados 32 cortadores de cana-de-açúcar do sexo masculino por meio de um questionário para sintomas de rinite, e marcadores inflamatórios em sangue periférico e lavado nasal, no período de entressafra, e em 3 e 6 meses após o início da colheita da cana-de-açúcar. Os dados climáticos e as concentrações de material particulado fino foram medidos no mesmo dia. Resultados: O material particulado fino na entressafra e em 3 e 6 meses de safra foi 27 (23-33 µg/m3), 112 (96-122 µg/m3) e 63 (17-263 µg/m3), respectivamente; a temperatura de 24 horas foi 32,6 (25,4º-37,4ºC), 32,3 (26,7º-36,7ºC) e 29,7 (24,1º-340ºC) e a umidade relativa do ar foi 45,4 (35,0%-59,7%), 47,9 (39,1%-63,0%), e 59,9 (34,7%-63,2%), na entressafra, 3 e 6 meses após o início da colheita. A idade foi de 37,4 ± 10,9 anos. A prevalência de sintomas de rinite foi significativamente maior em 3 meses da S (53,4%), comparado com a entressafra (26,7%; p = 0,039) e 6 meses da safra (20%; p = 0,006). As concentrações de interleucina 6 (IL-6) no lavado nasal aumentaram após 3 meses do início da colheita comparado com a entressafra (p = 0,012). A presença de sintomas de rinite, após 3 meses do início da colheita, foi diretamente associada com eosinófilos e inversamente associada com neutrófilos. Conclusões: Após 3 meses do início da colheita da cana-de-açúcar queimada, houve aumento na prevalência de sintomas de rinite e IL-6 em LN. Além disso, as contagens de eosinófilos foram diretamente associadas aos sintomas de rinite no período de maior concentração de material particulado.

Total IgE level in respiratory allergy: study of patients at high risk for helminthic infection

OBJETIVO: Eosinofilia e elevação de IgE sérica são expressões de atopia, contudo há fatores intervenientes como, por exemplo, as parasitoses intestinais. Esta pesquisa verifica a relação entre IgE sérica total, eosinófilos e IgE específica anti-áscaris em indivíduos portadores de asma e/ou rinite alérgica. MÉTODOS: Estudo do tipo transversal em adolescentes portadores de asma e/ou rinite alérgica que foram examinados quanto ao nível sérico de IgE total, de IgE anti-áscaris e de contagem dos eosinófilos sangüíneos. RESULTADOS: Foram analisados 101 pacientes com idade entre 12 e 21 anos. A mediana da IgE foi 660 UI/mL (P25-75 243,5-1500), e a dos eosinófilos foi 510 células/mm³ (P25-75 284-811). A IgE anti-áscaris foi positiva em 73 por cento (74/101) da amostra, mas houve apenas 33,7 por cento (34/101) de positividade ao parasitológico de fezes. Os coeficientes de correlação encontrados foram: 0,34 (p = 0,001) entre IgE total e eosinófilos, 0,52 (p < 0,001) entre IgE total e IgE anti-áscaris e 0,26 (p = 0,01) entre eosinófilos e IgE anti-áscaris. O modelo de regressão linear múltipla final encontrou que IgE anti-áscaris foi fator contribuinte para IgE sérica total com coeficiente de determinação (r2 ajustado) de 0,25 (F = 12,35; p < 0,001), e esse efeito foi independente de contagem de eosinófilos séricos e de parasitose intestinal por helmintos. CONCLUSÃO: Em pacientes com alergia respiratória e IgE sérica total bastante elevada, oriundos de áreas com alto risco de infecção por helmintos, a pesquisa de IgE anti-áscaris como possível fator explicativo pode ser de maior ajuda que a realização do parasitológico de fezes.

OBJECTIVE: Eosinophilia and increased serum IgE levels are indicators of atopy; however, other factors can also play a key role, such as intestinal parasitic infections. This study assesses the relationship between total serum IgE, eosinophil count, and anti-Ascaris IgE in individuals with asthma and/or allergic rhinitis. METHODS: A cross-sectional study was carried out in adolescents with asthma and/or allergic rhinitis. The patients had their total serum IgE, anti-Ascaris IgE and eosinophil count measured. RESULTS: A total of 101 patients aged 12 to 21 years were assessed. Median IgE level was 660 IU/mL (P25-75 243.5-1500), and the eosinophil count corresponded to 510 cells/mm³ (P25-75 284-811). Anti-Ascaris IgE was positive in 73 percent (74/101) of the individuals, but parasitological stool examination yielded positive results in only 33.7 percent (34/101). The correlation coefficients were the following: 0.34 (p = 0.001) between total IgE level and eosinophil count, 0.52 (p < 0.001) between total IgE level and anti-Ascaris IgE, and 0.26 (p = 0.01) between eosinophil count and anti-Ascaris IgE. The final multiple linear regression model pointed out that anti-Ascaris IgE contributed to a total serum IgE level with a coefficient of determination (adjusted R²) of 0.25 (F = 12.35; p < 0.001). This effect occurred regardless of eosinophil count and of the presence of intestinal helminthic infection. CONCLUSION: In patients with respiratory allergy and increased total serum IgE levels living in areas where there is a high risk for helminthic infections, the quantification of anti-Ascaris IgE can be more useful and more insightful than the parasitological stool examination.

IgE sérica total em atópicos e näo-atópicos na cidade de Porto Alegre / Total serum IgE level in atopic and non-atopic individuals in Porto Alegre, RS

OBJETIVO: Determinar em nossa cidade o nível sérico de IgE em indivíduos sadios, não- atópicos e em pacientes atópicos com manifestações respiratórias. MÉTODOS: Foram estudados 92 pacientes atópicos e 86 indivíduos sadios de ambos os sexos, classificados em grupos de acordo com faixa etária e sexo. A presença de atopia foi determinada através da história, exame físico e reatividade a testes cutâneos de puntura com alérgenos inalantes. A IgE sérica foi avaliada utilizando-se o sistema Pharmacia Immuno-Cap. RESULTADOS: Observou-se que o nível de IgE no soro é mais elevado no sexo masculino. Os valores médios de IgE total nos pacientes atópicos (401 UI/mL) são significativamente maiores que àqueles observados entre indivíduos não-atópicos (54,4 UI/mL). Através desse levantamento foi possível determinar os valores normais para as faixas etárias estudadas entre indivíduos sadios de Porto Alegre. CONCLUSÕES: Nosso estudo permitiu observar que o nível de IgE entre pacientes atópicos e indivíduos não-atópicos apresenta distribuição similar àquela verificada em outros países.