RESUMEN
Given the various clinical manifestations that characterize Coronavirus Disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant proteins A (SP-A) and D (SP-D) are collectins that play a crucial role in ensuring proper alveolar function and an alteration of their serum levels was reported in several pulmonary diseases characterized by Acute Respiratory Distress Syndrome (ARDS) and pulmonary fibrosis. Considering that such clinical manifestations can also occur during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. In this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n = 51) at admission (T0) and after seven days (T1) and compared with healthy donors (n = 11). SP-D increased in COVID-19 patients compared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. In light of these results, SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia, and the early detection of SP-D serum levels could be crucial for preventive clinical management.
Asunto(s)
Biomarcadores , COVID-19 , Proteína A Asociada a Surfactante Pulmonar , Proteína D Asociada a Surfactante Pulmonar , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/sangre , COVID-19/diagnóstico , Masculino , Femenino , Proteína D Asociada a Surfactante Pulmonar/sangre , Biomarcadores/sangre , Persona de Mediana Edad , Proteína A Asociada a Surfactante Pulmonar/sangre , SARS-CoV-2/aislamiento & purificación , Anciano , Adulto , PronósticoRESUMEN
In forensic cases, detailed identification of pneumonia is important. Our objective was to statistically determine the applicability of three interstitial lung disease (ILD) markers for forensic diagnosis using serum collected from dead bodies with various postmortem intervals (PMIs). We retrospectively analyzed the levels of postmortem serum Krebs von den Lungen-6 (KL-6) and pulmonary surfactant-associated proteins A and D (SP-A and SP-D) using 221 samples obtained during forensic autopsy at our facility from 2019 to 2023. We evaluated the diagnostic efficacy of ILD markers for various pneumonias against the pathological diagnosis, and examined the assessment of the severity of ILD. When comparing the ILD group with bacterial pneumonia (BP) versus the control group, there was a significant increase in KL-6 in the ILD group. When comparing the severe ILD (SILD) group with the mild ILD (MILD) group, there was a significant increase in KL-6 and SP-D in the SILD group. The optimal cutoff values for differentiating SILD were 607.0 U/mL for KL-6, 55.5 ng/mL for SP-A, and 160.0 ng/mL for SP-D, and the sensitivity/specificity (%) of KL-6, SP-A, and SP-D for SILD were 84.1/95.2, 55.6/85.7, and 66.7/74.6, respectively. This is the first study to examine KL-6 in postmortem serum in forensic medicine. By analyzing dead bodies with various PMIs, our results confirmed statistically that postmortem serum KL-6 specifically detects ILD, postmortem serum SP-A has high sensitivity to lung injury, and postmortem serum SP-D is potentially useful in assessing the severity of ILD.
Asunto(s)
Biomarcadores , Enfermedades Pulmonares Intersticiales , Mucina-1 , Proteína A Asociada a Surfactante Pulmonar , Proteína D Asociada a Surfactante Pulmonar , Humanos , Mucina-1/sangre , Enfermedades Pulmonares Intersticiales/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Biomarcadores/sangre , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Proteína A Asociada a Surfactante Pulmonar/sangre , Anciano , Adulto , Sensibilidad y Especificidad , Anciano de 80 o más Años , Neumonía/sangre , Patologia Forense , Neumonía Bacteriana/sangre , Neumonía Bacteriana/diagnósticoRESUMEN
BACKGROUND: The correlation between COVID-19 and RT has not been determined to date and remains a clinical question. The aim of this study was to evaluate coronavirus disease 2019 (COVID-19) pneumonia before, during, and after radiation therapy (RT) regarding the radiation doses, radiation pneumonitis, and surfactant protein levels. METHODS: We evaluated patients diagnosed with COVID-19 before, during, or after RT for the lung between August 2020 and April 2022. In patients with breast cancer, the RT dose to the ipsilateral lung was determined. In all other patients, bilateral lung RT doses were determined. Patients diagnosed with COVID-19 after RT were evaluated to determine whether radiation pneumonitis had worsened compared with before RT. The serum levels of the surfactant proteins SP-A and SP-D were measured before, during, and after RT. RESULTS: The patients included in the study comprised three men (27.3%) and eight women (72.7%). The primary cancer sites were the breast (n = 7; 63.7%), lung (n = 2; 18.1%), esophagus (n = 1; 9.1%), and tongue (9.1%). COVID-19 was diagnosed before RT in four patients, during RT in two patients, and after RT in five patients. Six (54.5%) patients developed COVID-19 pneumonia. Radiation pneumonitis grade ≥2 was not identified in any patient, and radiation pneumonitis did not worsen after RT in any patient. No rapid increases or decreases in SP-A and SP-D levels occurred after the diagnosis of COVID-19 in all patients regardless of RT timing. CONCLUSIONS: COVID-19 did not appear to result in lung toxicity and surfactant protein levels did not change dramatically.
Asunto(s)
COVID-19 , Pulmón , Proteína A Asociada a Surfactante Pulmonar , Proteína D Asociada a Surfactante Pulmonar , Neumonitis por Radiación , Femenino , Humanos , Masculino , COVID-19/sangre , COVID-19/epidemiología , Pulmón/efectos de la radiación , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Proteína D Asociada a Surfactante Pulmonar/sangre , Neumonitis por Radiación/epidemiología , Proteína A Asociada a Surfactante Pulmonar/sangre , Neoplasias de la Mama/radioterapiaRESUMEN
BACKGROUND: Nintedanib is effective for treating idiopathic pulmonary fibrosis (IPF), but some patients may exhibit a suboptimal response and develop on-treatment acute exacerbation (AE-IPF), hepatic injury, or mortality. It remains unclear which patients are at risk for these adverse outcomes. METHODS: We analysed the demographic and clinical data, baseline plasma levels of Krebs von den Lungen-6 (KL-6) and surfactant protein A (SPA), and longitudinal clinical courses of a real-world cohort of IPF patients who received nintedanib ≥ 14 days between March 2017 and December 2020. Cox proportional-hazards regression, subdistribution hazards regression, and sensitivity analyses were performed to investigate the association between baseline predictors and AE-IPF, mortality, and nintedanib-related hepatic injury. The relationship between baseline predictors and pulmonary function decline was determined. RESULTS: Fifty-seven patients were included, of whom 24 (42%) developed hepatic injury, 20 (35%) had AE-IPF, and 16 (28%) died on-treatment. A baseline plasma KL-6 level ≥ 2.5 ng/mL, and diffusion capacity for carbon monoxide (DLCO) < 55% predicted, were associated with increased risk of hepatic injury (adjusted hazard ratio [aHR] was 3.46; 95% CI 1.13-10.60; p = 0.029 for KL-6, and 6.05; 95% CI 1.89-19.32; p = 0.002 for DLCO). Both factors also predicted severe and recurrent hepatic injury. Patients with baseline KL-6 ≥ 2.5 ng/mL also had a higher risk of AE-IPF (aHR 4.52; 95% CI 1.63-12.55; p = 0.004). For on-treatment mortality, baseline KL-6 ≥ 3.5 ng/mL and SPA ≥ 600 pg/mL were significant predictors (aHR 5.39; 95% CI 1.16-24.97; p = 0.031 for KL-6, and aHR 12.28; 95% CI 2.06-73.05; p = 0.006 for SPA). Results from subdistribution hazard regression and sensitivity analyses supported these findings. Patients with elevated baseline plasma KL-6 levels also exhibited a trend towards faster pulmonary function decline. CONCLUSIONS: For patients with IPF who are receiving nintedanib, we have identified baseline predictors, in particular plasma KL-6 levels, for the risk of adverse outcomes. Patients with these predictors may require close monitoring for unfavourable responses during treatment. Our findings also support the prognostic role of molecular markers like KL-6 and may contribute to future formulation of more individualized therapeutic strategies for IPF.
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Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Indoles/uso terapéutico , Mucina-1/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Fibrosis Pulmonar Idiopática/sangre , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
Coronavirus disease 2019 (COVID-19) is globally rampant, and to curb the growing burden of this disease, in-depth knowledge about its pathophysiology is needed. This was an observational study conducted at a single center to investigate serum cytokine and chemokine levels of COVID-19 patients, based on disease severity. We included 72 consecutive COVID-19 patients admitted to our hospital from March 21 to August 31, 2020. Patients were divided into Mild-Moderate I (mild) and Moderate II-Severe (severe) groups based on the COVID-19 severity classification developed by the Ministry of Health, Labor and Welfare (MHLW) of Japan. We compared the patient characteristics as well as the serum cytokine and chemokine levels on the day of admission between the two groups. Our findings indicated that the severe group had significantly higher levels of serum fibrinogen, d-dimer, lactate dehydrogenase, C-reactive protein, ferritin, Krebs von den Lungen-6, surfactant protein (SP)-D, and SP-A than the mild group. Strikingly, the levels of interleukin (IL)-28A/interferon (IFN)-λ2 were significantly lower in the severe group than in the mild group. We believe that reduced levels of type III interferons (IFN-λs) and alterations in the levels of other cytokines and chemokines may impact the severity of the disease.
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COVID-19/sangre , Quimiocinas/sangre , Interferones/sangre , SARS-CoV-2/inmunología , Adulto , Anciano , Proteína C-Reactiva/análisis , COVID-19/patología , Regulación hacia Abajo , Femenino , Ferritinas/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Humanos , Interferones/biosíntesis , Interleucinas/sangre , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Mucina-1/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Índice de Severidad de la Enfermedad , Interferón lambdaAsunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Indio/toxicidad , L-Lactato Deshidrogenasa/sangre , Enfermedades Pulmonares/sangre , Enfermedades Profesionales/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Adulto , Contaminantes Ocupacionales del Aire/análisis , Biomarcadores/sangre , Biomarcadores/orina , Monitoreo del Ambiente , Femenino , Humanos , Indio/análisis , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/orina , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/orina , Exposición Profesional/efectos adversos , Exposición Profesional/análisisRESUMEN
ABSTRACT: Interstitial pneumonia with autoimmune features (IPAF) is a special subtype of interstitial lung disease that has received worldwide attention. Krebs von den Lungen-6 (KL-6) and surfactant protein-A (SP-A) can be used as an important biomarker of interstitial lung disease, but its exact relationship with IPAF is poorly understood.A total of 65 IPAF patients were included in the study and were followed up for 52âweeks. The KL-6 and SP-A were evaluated by chemiluminescence enzyme immunoassay. The above indicators were tested at 2 time points, baseline (the first admission of patients) and 52âweeks. We also collected the indicators of antinuclear antibodies and rheumatoid factor. Based on high-resolution computed tomography evaluations, patients were divided into: aggravation, stable, and improvement group. At same time, 30 age-matched normal people as normal control were recruited, the same information was collected. Correlations among the groups were compared and analyzed.The KL-6 and SP-A level in IPAF patients were significantly higher than normal controls (fold increaseâ=â11.35 and 1.39, both Pâ<â.001) and differed significantly at baseline and 52âweeks in IPAF (difference ratioâ=â37.7% and 21.3%, Pâ<â.05, both). There were significant differences at baseline and 52âweeks (r values of aggravation, improvement, and stable groups for KL-6 were 0.705, 0.770, and 0.344, Pâ=â.001, .001, and .163, and for SP-A the r value were 0.672, 0.375, and 0.316, Pâ=â.001, .126, and .152). In aggravation group, KL-6 and SP-A were correlated with CT scores (both Pâ<â.05). Diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC), % predicted showed a progressive downward trend, with a significant difference at baseline and 52âweeks in IPAF patients (difference ratioâ=â23.8% and 20.6%, both Pâ<â.05). There was a significant correlation between KL-6 and FVC % predicted and DLCO (both Pâ<â.05), SP-A showed negatively correlated with DLCO, but not significantly correlated with FVC % predicted (Pâ<â.05 and .47).This study demonstrated that KL-6 and SP-A can reflect disease progression, and both 2 play a key role at reflection of lung epithelial cell injury and fibrosis degree in IPAF.
Asunto(s)
Enfermedades Pulmonares Intersticiales/sangre , Mucina-1/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Adulto , Anticuerpos Antinucleares/sangre , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Humanos , Pulmón/inmunología , Pulmón/patología , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Factor Reumatoide/sangreRESUMEN
BACKGROUND: Some patients with interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. This study aimed to evaluate whether serial changes in the serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression. METHODS: Sixty-four patients with IPAF and 41 patients with non-fibrotic lung disease (non-FLD) were examined. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (n = 9), an improvement group (n = 13), and a stable group (n = 14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut-off value, and area under the curve (AUC) value for each of the indices were determined using receiver operating characteristic (ROC) curve analysis. The expression differences in these biomarkers and their correlation with disease severity were analyzed. RESULTS: Compared with non-FLD patients, serum SP-A and KL-6 levels in IPAF patients were increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and negatively correlated with DLCO (SP-A: rS = - 0.323, p = 0.018; KL-6: rS = - 0.348, p = 0.0011). In patients with progressive disease, the posttreatment serum SP-A and KL-6 levels were increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In patients showing improvement, the levels were decreased significantly [SP-A (p = 0.007) and KL-6 (p = 0.002)]. Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001). CONCLUSIONS: Serum SP-A and KL-6 offer high sensitivity and specificity for the diagnosis of IPAF. The decrease in serum SP-A and/or KL-6 levels in patients with IPAF is related to the improvement in pulmonary function. SP-A and KL-6 may be important biomarkers for predicting disease progression in patients with IPAF.
Asunto(s)
Neumonías Intersticiales Idiopáticas/sangre , Neumonías Intersticiales Idiopáticas/diagnóstico , Mucina-1/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Curva ROC , Pruebas de Función Respiratoria , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
About 15% of pregnant women undergo missed abortion (MA), wherein women do not experience cramping and vaginal bleeding. Dysregulation of the immune molecules and steroid hormones contribute to early pregnancy loss. Collectins- surfactant protein A (SP-A), surfactant protein D (SP-D), and mannose-binding lectin (MBL) are a group of innate immune molecules regulated by the steroid hormones. Reduced levels of SP-A and SP-D during the early gestation exhibited a significant association with the severe early onset preeclampsia. In order to determine the serum profile of collectins throughout the normal pregnancy and explore their predictive potential during the 8-12 weeks of gestation for MA, we examined a prospective cohort of pregnant women (n = 221). The serum levels of SP-A and SP-D were significantly downregulated in the normal pregnant women in all the three trimesters (n = 30) compared with the non-pregnant women (n = 20) and were not significantly different across the three trimesters. Fourteen of the women from the cohort underwent MA during the 14-20 weeks of gestation and exhibited a significant downregulation in the serum levels of SP-D during 8-12 weeks of gestation. A significant inhibition of the HTR-8/SVneo cell proliferation and migration in the presence of a recombinant fragment of human SP-D suggested the relevance of SP-D in placental development. We report here that the serum levels of SP-A, SP-D, and MBL are consistently maintained during pregnancy in the Indian cohort. Dysregulated serum levels of SP-D and P4/E2 ratio during the early first trimester may predict occurrence of MA.
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Aborto Retenido/sangre , Lectina de Unión a Manosa/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Adulto , Proteínas de Arabidopsis/fisiología , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Embarazo , Estudios Prospectivos , Proteína D Asociada a Surfactante Pulmonar/farmacología , Factores de Transcripción/fisiología , Trofoblastos/efectos de los fármacosRESUMEN
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is the leading cause of morbidity and mortality across the globe. Currently, there is a dearth of biomarkers which can accurately diagnose and evaluate the prognosis of the disease. Systemic Surfactant Protein- A (SP-A) levels are generally higher in smokers compared to non-smokers as well as elevated in COPD patients as compared to controls. The objective of the study was to estimate and compare plasma surfactant protein-A levels in male and female COPD patients and healthy subjects and to evaluate the role of SP-A as a possible bio-marker for COPD patients. METHODS: A Comparative study, conducted at the department of Physiology & Cell Biology, University of Health Sciences, Lahore between August 2013 and April 2015. A total of 84 subjects of both sexes between 30-80 years of age were included in this study. Subjects were taken from local community and were divided into four groups (A- D). COPD was diagnosed on the basis of relevant history and spirometry showing post bronchodilator FEV1/FVC <0.70. RESULTS: Plasma SP-A levels were not different between controls and COPD patients and between male and female COPD patients. However, SP-A levels were directly correlated with cotinine levels (r= 0.503, p=0.001). Female patients were usually more symptomatic than males and developed COPD at an earlier age compared with male patients. CONCLUSION: Plasma SP-A levels were not significantly different between groups. Plasma cotinine levels (an indication of the tobacco use) were positively correlated with plasma SP-A levels in study subjects. Female patients developed COPD at an early age compared to male counterparts with similar tobacco exposure.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Factores Sexuales , Espirometría , TensoactivosRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fibrosing lung disease with poor prognosis. Pirfenidone and nintedanib are anti-fibrotic drugs used for patients with IPF. These drugs reduce the rate of decline in forced vital capacity (FVC). Serum surfactant protein (SP)-A, SP-D, and Krebs von den Lungen-6 (KL-6) are monitoring and prognostic biomarkers in patients with IPF; however, their relationship with the therapeutic outcomes of anti-fibrotic drugs has not been investigated. We aim to clarify whether serum SP-A, SP-D, and KL-6 reflect therapeutic outcomes of pirfenidone and nintedanib administration in patients with IPF. METHODS: We retrospectively investigated patients with IPF who were initiated on pirfenidone or nintedanib administration between January 2014 and June 2018 at our hospital. Changes in clinical parameters and serum SP-A, SP-D, and KL-6 levels were evaluated. Patients with ≥10% decline in FVC or ≥ 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as progression group, while the other patients were classified as stable group. RESULTS: Forty-nine patients were included (pirfenidone, 23; nintedanib, 26). Stable group comprised 32 patients, while progression group comprised 17 patients. In the stable group, changes in SP-A and KL-6 from baseline to 3 and 6 months significantly decreased compared with the progression group (SP-A: 3 months - 6.0% vs 16.7%, 6 months - 10.2% vs 20.2%, KL-6: 3 months - 9.2% vs 6.7%, 6 months - 15.0% vs 12.1%, p < 0.05). Changes in SP-A and SP-D levels showed significant negative correlations with the change in %FVC (r = - 0.46 and r = - 0.39, p < 0.01, respectively) and %DLco (r = - 0.67 and r = - 0.54, p < 0.01, respectively). Similar results were also seen in subgroup analysis for both pirfenidone and nintedanib groups. On logistic regression analysis, decrease in SP-A from baseline to 3 months and 6 months was found to predict the outcomes at 6 months (odds ratios: 0.89 and 0.88, respectively). CONCLUSIONS: Changes in serum SP-A reflected the outcomes of anti-fibrotic drug therapy. Serum SP-A has a potential as a biomarker of therapeutic outcomes of anti-fibrotic drugs.
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Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Mucina-1/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Anciano , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/sangre , Indoles/uso terapéutico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Piridonas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Capacidad VitalRESUMEN
To evaluate the effect of coal-burning arsenic (As) exposure on lung function and the potential underlying mechanisms, a total of 217 As-exposed subjects and 75 reference subjects were recruited into this study. Hair arsenic (H-As), pulmonary function tests, and serum inflammatory markers CC16, SP-A, MMP-9, and TIMP-1 were evaluated. Residents from As-exposed areas showed higher H-As concentrations (median 0.25 µg/g) than subjects from the reference area (median 0.14 µg/g). Large reductions in lung function parameters were noted in the As-exposed group. A significant negative correlation was observed between H-As concentrations and lung function. Specifically, monotonic negative dose-response relationships were observed between H-As and FEV1(%), FEV1/FVC (%) and FEF75 (%) (all P < 0.05), while the associations between H-As and FVC (%), FEF25 (%), and FEF50 (%) were nonlinear (P for nonlinearity = 0.03, 0.001, 0.01, respectively). In addition, there was a direct positive relationship between H-As and the inflammatory response. Alterations in inflammatory biomarkers (CC16, SP-A, MMP-9, and MMP-9/TIMP-1) were significantly associated with As-induced lung function impairment. Thus, this population-based study revealed that As exposure has significant toxic effects on lung function and increased inflammation may occur during this toxic process. We provide scientific evidence for an As-induced alteration in inflammatory biomarkers and pulmonary damage in an As-exposed population. The results of this study can inform risk assessment and risk control processes in relation to human As exposure in coal-burning arsenicosis areas.
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Intoxicación por Arsénico/fisiopatología , Arsénico/análisis , Carbón Mineral , Contaminantes Ambientales/análisis , Pulmón/fisiopatología , Adulto , Intoxicación por Arsénico/sangre , Intoxicación por Arsénico/epidemiología , Intoxicación por Arsénico/metabolismo , Monitoreo Biológico , China/epidemiología , Femenino , Cabello/química , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Proteína A Asociada a Surfactante Pulmonar/sangre , Pruebas de Función Respiratoria , Inhibidor Tisular de Metaloproteinasa-1/sangre , Uteroglobina/sangreRESUMEN
PROBLEM: Preeclampsia (PE), a multifactorial disorder characterized by impaired placental development, elevated inflammatory response and dysregulated placental steroidogenesis. PE may be preventable if predicted early on. METHOD OF STUDY: The study evaluated the potential of immunomodulatory collectins, surfactant protein A (SP-A), surfactant protein D (SP-D), and mannose binding lectin (MBL), to predict PE before the disease onset, in a prospective study cohort of healthy pregnant women (n = 922). In addition, a cross-sectional study was conducted to determine the serum and placental profile of collectins in PE women after the disease onset (early-onset PE [EOPE], n = 33; late-onset PE [LOPE], n = 24); and controls [n = 75]. The serum profiles of estradiol (E2) and progesterone (P4) were evaluated to determine their correlation with collectins. RESULTS: In the prospective cohort, significantly decreased serum levels of SP-A, SP-D, P4/E2 ratio were observed in women who subsequently developed severe EOPE. Interestingly, after the disease onset, there was a significant increase in serum and placental levels of collectins in women with severe EOPE, whereas women with LOPE had significantly decreased levels of collectins. Serum P4/E2 ratio was significantly altered in severe EOPE and positively correlated with serum levels of SP-A and SP-D. CONCLUSION: Collectins are differentially expressed in the serum during progression of PE. Decreased serum levels of SP-A, SP-D, P4/E2 ratio and increased E2 during 10-20 weeks of gestation are novel plausible risk factors for early prediction of EOPE in Indian women.
Asunto(s)
Estradiol/sangre , Preeclampsia/sangre , Progesterona/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Adulto , Colectinas/análisis , Colectinas/sangre , Estudios Transversales , Diagnóstico Precoz , Estradiol/análisis , Femenino , Regulación de la Expresión Génica , Humanos , Placenta/química , Embarazo , Proteínas Gestacionales/biosíntesis , Proteínas Gestacionales/genética , Primer Trimestre del Embarazo/sangre , Progesterona/análisis , Estudios Prospectivos , Proteína A Asociada a Surfactante Pulmonar/análisis , Proteína A Asociada a Surfactante Pulmonar/biosíntesis , Proteína A Asociada a Surfactante Pulmonar/genética , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/biosíntesis , Proteína D Asociada a Surfactante Pulmonar/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto JovenRESUMEN
Acute kidney injury (AKI) is associated with widespread effects on distant organs, including the lungs. Surfactant protein (SP)-A and SP-D are members of the C-type lectin family, which plays a critical role in host defense and regulation of inflammation in a variety of infections. Serum levels of SP-A and SP-D are markers to reflect lung injury in acute respiratory distress syndrome, idiopathic pulmonary fibrosis, and sarcoidosis. We investigated the change of lung-specific markers, including SP-A and SP-D in an AKI mice model. We studied C57BL/6J mice 4 and 24 hours after an episode of ischemic AKI (23 min of renal pedicle clamping and then reperfusion); numerous derangements were present, including SP-A, SP-D, and lung tight-junction protein. Neutrophil infiltration and apoptosis in the lungs increased in ischemic AKI. Receptor for advanced glycation end products (RAGE) in the lungs, a marker of pneumocyte I, was not changed. Lung tight-junction proteins, particularly claudin-4, claudin-18, and anti-junctional adhesion molecule 1 (JAMA-1), were reduced in 24 hours after AKI. Serum SP-A and SP-D significantly increased in ischemic AKI. SP-A and SP-D in the lungs did not increase in ischemic AKI. The immunohistochemistry showed that the expression of SP-A and SP-D was intact in ischemic AKI. SP-A and SP-D in the kidneys were significantly higher in AKI than in the sham. These patterns of SP-A and SP-D in the kidneys were similar to those of serum. AKI induces apoptosis and inflammation in the lungs. Serum SP-A and SP-D increased in ischemic AKI, but these could have originated from the kidneys. So serum SP-A and SP-D could not reflect lung injury in AKI. Further study is needed to reveal how a change in lung tight-junction protein could influence the prognosis in patients with AKI.
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Lesión Renal Aguda/patología , Proteína A Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/análisis , Daño por Reperfusión/patología , Lesión Renal Aguda/sangre , Animales , Apoptosis , Riñón/patología , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , Proteína A Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Daño por Reperfusión/sangreRESUMEN
BACKGROUND: The objective of this study was to evaluate the diagnostic value of serological markers Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), SP-D, chemokine ligand 2 (CCL2), and chemokine 13 (CXCL13) in idiopathic interstitial pneumonia (IIP). METHODS: Patients with IIP aged 18-80 years from the First Affiliated Hospital of Guangzhou Medical University were enrolled in this retrospective case-control study. Data on the general patient characteristics, laboratory test results, chest high-resolution CT, and pulmonary function test results were collected. The diagnosis of idiopathic pulmonary fibrosis (IPF) was based on the international practice guidelines for the diagnosis and treatment of IPF, a collaborative effort published by the American Thoracic Society (ATS)/European Respiratory Association (ERS), Japanese Respiratory Society, and Latin American Thoracic Society. The diagnostic criteria of non-IPF (N-IPF) followed the consensus classification of the IIPs, which was jointly issued by the ATS and ERS in 2002. The diagnosis of interstitial pneumonia with autoimmune features (IPAF) was based on the official research statement on IPAF, which was jointly issued by the ATS and ERS in 2015. Serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were measured. The differences in the expression of these biomarkers and their correlation with the severity of the disease were analyzed. The sensitivity, specificity, cutoff value, and area under the curve (AUC) value for each of the indices were determined using the receiver operating characteristic (ROC) curve analysis. FINDINGS: Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, -SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. The detection of these markers was found to have better diagnostic efficacy in patients with IIP than in those with pneumonia. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93-0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the diffusing capacity of the lungs for carbon monoxide (DLCO; r = -0.36, -0.37, -0.36, -0.30, respectively; all p < 0.05). Although their expression levels along with that of SP-D were elevated in patients with IPF, N-IPF, and IPAF, it was difficult to distinguish between these 3 conditions by detecting the 5 serum biomarkers together. Our findings indicate that the serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enriched the study on serum markers for IIPs. Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93-0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the DLCO (r = -0.36, -0.37, -0.36, -0.30, respectively; all p < 0.05). Our findings indicate that the serum levels of KL-6, -SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enrich the study on serum markers in IIPs. INTERPRETATION: Although the combined detection of KL-6, CCL3, and CXCL13 significantly improves the diagnosis of IIP, detection of all the 5 markers together is unable to distinguish between IPF, N-IPF, and IPAF.
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Quimiocina CCL2/sangre , Neumonías Intersticiales Idiopáticas/sangre , Neumonías Intersticiales Idiopáticas/diagnóstico , Mucina-1/sangre , Proteína A Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Adolescente , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Estudios de Casos y Controles , Quimiocina CXCL13/sangre , China , Humanos , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Curva ROC , Valores de Referencia , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenAsunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Biomarcadores/sangre , Enfermedades Pulmonares Intersticiales/enzimología , Anciano , Antagonistas de Receptores de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Estudios Transversales , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Masculino , Metaloproteinasa 7 de la Matriz/sangre , Persona de Mediana Edad , Estudios Prospectivos , Proteína A Asociada a Surfactante Pulmonar/sangre , Tomografía Computarizada por Rayos XRESUMEN
SSc is a rare disease of unknown origin associated with multiple organ involvement. One of the major complications that drives the mortality of SSc patients is interstitial lung disease. The course of SSc-interstitial lung disease progression has a wide spectrum. Since the treatment is based on aggressive immunosuppression it should not be given to stable or non-progressing disease. The correct identification of disease with high risk of progression remains a challenge for early therapeutic intervention, and biomarkers remain urgently needed. In fact, eight categories of biomarkers have been identified and classified according to the different biological pathways involved. The purpose of this article is to describe the main biomarkers thought to be of interest with clinical value in the diagnosis and prognosis of SSc-interstitial lung disease.
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Biomarcadores/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , Proteínas de Fase Aguda/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/sangre , Citocinas/sangre , Progresión de la Enfermedad , Humanos , Metaloproteinasas de la Matriz/sangre , Mucina-1/sangre , Pronóstico , Proteína A Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/sangreRESUMEN
Rice accumulates arsenic, an established lung toxicant. Little is known about the association of rice consumption with arsenic-related health effects, particularly interstitial lung disease. Between 2000 and 2002, 6,814 white, black, Hispanic, and Chinese adults from 6 US cities were enrolled in the Multi-Ethnic Study of Atherosclerosis. We included 2,250 participants who had spirometry data, 2,557 with full-lung computed tomography (CT) scans, and 5,710 with cardiac CT scans. Rice consumption and 310 participants with urinary arsenic were assessed at baseline. Spirometry and full-lung CT-derived measures of total lung capacity and high attenuation area (HAA), and interstitial lung abnormalities were measured at examination 5. Cardiac CT-derived HAA was measured at 1-3 visits. Twelve percent of participants reported eating at least 1 serving of rice daily. Comparing data between that group with those who ate less than 1 serving weekly, the mean difference for forced vital capacity was -102 (95% confidence interval (CI): -198, -7) mL, and for forced expiratory volume in 1 second was -90 (95% CI: -170, -11) mL after adjustment for demographics, anthropometrics, dietary factors, and smoking. The cross-sectional adjusted percent difference for total lung capacity was -1.33% (95% CI: -4.29, 1.72) and for cardiac-based HAA was 3.66% (95% CI: 1.22, 6.15). Sensitivity analyses for urinary arsenic were consistent with rice findings. Daily rice consumption was associated with reduced lung function and greater cardiac-based HAA.
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Enfermedades Pulmonares Intersticiales/etiología , Oryza/efectos adversos , Anciano , Anciano de 80 o más Años , Arsénico/orina , Aterosclerosis/etnología , Biomarcadores/sangre , Biomarcadores/orina , Dieta , Femenino , Volumen Espiratorio Forzado , Humanos , Estudios Longitudinales , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Oryza/química , Proteína A Asociada a Surfactante Pulmonar/sangre , Pruebas de Función Respiratoria , Estados Unidos , Capacidad VitalRESUMEN
Background: Antifibrotic agents have been approved for the treatment of idiopathic pulmonary fibrosis (IPF). However, the efficacy of these drugs in the treatment of familial IPF (FIPF) has not been previously reported. Case presentation: We report the case of a 77-year-old man with FIPF, successfully treated with pirfenidone. His uncle died due to IPF, and his niece was diagnosed with the disease. He had worsening dyspnea two months prior to admission to our hospital. Upon admission, he had desaturation when exercising and broad interstitial pneumonia. Administration of pirfenidone improved his dyspnea, desaturation, and the reticular shadow on his chest radiograph. Increased fibrotic marker levels KL-6 and SP-D were also normalized in six months; treatment had no effect on his serum periostin level. Pirfenidone has been effective for over two years. Conclusion: Antifibrotic agents such as pirfenidone may be useful for the management of FIPF, as well as cases of sporadic IPF.
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Moléculas de Adhesión Celular/análisis , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Piridonas/farmacología , Anciano , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Moléculas de Adhesión Celular/sangre , Tos/etiología , Progresión de la Enfermedad , Disnea/etiología , Humanos , Masculino , Mucina-1/análisis , Mucina-1/sangre , Proteína A Asociada a Surfactante Pulmonar/análisis , Proteína A Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/sangre , Piridonas/uso terapéuticoRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible condition with poor prognosis that is characterized by a variable clinical course in each patient, which renders it a complex disease with unknown causes. Despite the proven efficacy of novel antifibrotic therapies, including pirfenidone and nintedanib, the diagnosis and follow-up of IPF remain challenging. Hence, the identification of molecular biomarkers for early detection of IPF and to predict biologically determined individual clinical courses, has recently piqued the interest of researchers. Previous studies have demonstrated the diagnostic and prognostic efficacy of blood proteins such as KL-6, Surfactant protein (SP)-A, and SP-D, in patients with IPF. Due to their use in clinical practice in Japan, for approximately twenty years, a significant amount of data about these biomarkers has been accumulated. This paper reviews the recent literature on molecular biomarkers for IPF that have been developed in Japan as well as other potential molecular biomarkers.