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
INTRODUCTION: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry. METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3). RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low. CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.
Asunto(s)
Biomarcadores , Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales , Sistema de Registros , Humanos , Masculino , Femenino , Persona de Mediana Edad , Capacidad Vital , Anciano , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/diagnóstico , Fibrosis Pulmonar/fisiopatología , Fibrosis Pulmonar/diagnóstico , Proteína D Asociada a Surfactante Pulmonar/sangre , Pulmón/fisiopatología , Valor Predictivo de las Pruebas , Proteína 1 Similar a Quitinasa-3/sangre , Quimiocinas CC , Osteopontina , Receptor para Productos Finales de Glicación Avanzada/sangre , Fibrosis Pulmonar Idiopática/fisiopatología , Fibrosis Pulmonar Idiopática/diagnósticoRESUMEN
BACKGROUND: Radiation-induced lung disease is a potentially fatal, dose-limiting toxicity commonly seen after radiotherapy of thoracic malignancies, including breast cancer. AIM: To evaluate and compare the early lung toxicity induced by 3D-CRT and IMRT radiotherapy treatment modalities in breast cancer female patients using biochemical, dosimetry and clinical data. SUBJECTS AND METHODS: this study included 15 normal healthy controls, 15 breast cancer patients treated with IMRT, and 15 breast cancer patients treated with 3D-CRT. One blood sample was obtained from the control group and 3 blood samples were withdrawn from cases before RT, after RT and after 3 months of RT. RESULT: IMRT delivered higher radiation dose to the breast tumor and lower doses to the lung as an organ at risk. There was a non-significant increase in the serum levels of IL-6 before IMRT and 3D-CRT compared with its levels in the control group. There were significant increases in serum levels of IL-6 after RT (IMRT and 3DCRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of IL-6 after 3 months of RT (IMRT and 3D-CRT) compared with its serum levels immediately after RT. There was a non-significant increase in the serum levels of SP-D before RT (IMRT and 3D-CRT) compared with its levels in the control group. There were significant-increases in serum levels of SP-D after RT (IMRT and 3D-CRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of SP-D after 3 months of radiotherapy (IMRT and 3D-CRT) compared with its serum levels immediately after RT. CONCLUSION: serum of levels IL-6 and SP-D can be used to diagnose the occurrence of early lung toxicity due to radiotherapy and the rate of recovery from radiation pneumonitis is apparent in case of IMRT than 3D-CRT.
Asunto(s)
Neoplasias de la Mama , Interleucina-6 , Proteína D Asociada a Surfactante Pulmonar , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada , Humanos , Femenino , Interleucina-6/sangre , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/sangre , Persona de Mediana Edad , Proteína D Asociada a Surfactante Pulmonar/sangre , Estudios de Casos y Controles , Radioterapia Conformacional/efectos adversos , Estudios de Seguimiento , Adulto , Traumatismos por Radiación/sangre , Traumatismos por Radiación/etiología , Pronóstico , Neumonitis por Radiación/etiología , Neumonitis por Radiación/sangre , Planificación de la Radioterapia Asistida por Computador/métodos , Pulmón/efectos de la radiación , Anciano , RadiometríaRESUMEN
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: Obstructive sleep apnea (OSA) has been identified as a possible contributor to interstitial lung disease. While positive airway pressure (PAP) is effective therapy for OSA, it causes large increases in lung volumes during the night that are potentially deleterious, analogous to ventilator-induced lung injury, although this has not been previously studied. The goal of this study was to assess the impact of PAP therapy on four biomarkers of alveolar epithelial and endothelial injury and extracellular matrix remodeling in patients with OSA. METHODS: In 82 patients with moderate to severe OSA who were adherent to PAP therapy, surfactant protein D, osteopontin, angiopoietin-2, and matrix metalloprotease-7 were measured by ELISA in serum samples collected before and 3- to 6-months after initiation of PAP therapy. RESULTS: An increase in angiopoietin-2 level of 0.28 ng/mL following PAP therapy was observed (p = 0.007). This finding was replicated in an independent sample of OSA patients. No significant change was detected in surfactant protein D, osteopontin, or matrix metalloprotease-7. CONCLUSIONS: This finding raises concern for a possible adverse impact of PAP therapy on vascular endothelium.
Asunto(s)
Angiopoyetina 2 , Presión de las Vías Aéreas Positiva Contínua , Apnea Obstructiva del Sueño , Angiopoyetina 2/administración & dosificación , Humanos , Metaloproteasas/sangre , Osteopontina/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/terapiaRESUMEN
BACKGROUND: Surfactant protein D (SP-D) is a critical component of the innate immune system intrinsically linked to energy metabolism. However, the relationship of SP-D gene polymorphisms and gestational diabetes mellitus (GDM) remains unclear. In this study, we analyzed SP-D gene polymorphisms in GDM patients and nondiabetic controls and then determined the association of SP-D gene polymorphisms with GDM. METHODS: We examined a common genetic polymorphism located in the SP-D coding region (rs721917, Met31Thr) in GDM patients (n = 147) and healthy pregnant controls (n = 97) by using a cleaved amplification polymorphism sequence-tagged sites (PCR-RFLP) technique. The level of SP-D protein in the serum of GDM patients and nondiabetic controls was determined by ELISA. The gene and allele frequencies of SP-D and their association with GDM as well as SP-D protein levels were analyzed and expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: We found that there was a significant association of the SP-D polymorphism (rs721917) with GDM. The SP-D (T/T) genotype was found in 11.6% and 21.6% of GDM patients and matched healthy controls, respectively (odds ratio, 0.473; 95% confidence interval, 0.235-0.952; P = 0.033), indicating that women with the (T/T) genotype had a lower prevalence of GDM (OR = 0.473). Women with the T/C genotype showed an increased risk of GDM (odds ratio, 2.440; 95% confidence interval, 1.162-5.123; P = 0.017). We did not observe corrections between glucose homeostasis markers and SP-D genotypes in women with GDM. Furthermore, serum SP-D levels were higher in GDM patients than in matched healthy controls. CONCLUSIONS: This study found the first evidence that an SP-D gene polymorphism (rs721917) was associated with GDM, which may provide the basis for further study on how SP-D plays a regulatory role in GDM.
Asunto(s)
Diabetes Gestacional/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteína D Asociada a Surfactante Pulmonar/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Diabetes Gestacional/sangre , Femenino , Humanos , Embarazo , Proteína D Asociada a Surfactante Pulmonar/sangre , Adulto JovenRESUMEN
COPD is the fourth leading cause of mortality, and is predicted to be the third leading cause of death worldwide by 2020. But few studies on Tibetan COPD of China. This study identifies distinctive miRNA signatures in Tibetan COPD patients from Tibetan healthy subjects that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. In this study, a total of 210 differentially expressed miRNAs were screened. Analysis of the functions of target genes of differentially expressed miRNAs via GO enrichment analysis revealed that they mainly influenced guanyl-nucleotide exchange factor activity, cell morphogenesis and the positive regulation of GTPase activity. KEGG pathway enrichment analysis showed that these target genes were mainly enriched in signaling by NGF, Axon guidance, developmental biology, ubiquitin mediated proteolysis, and PDGF signaling pathways. MiR-106-5p and miR-486-5p expression was validated in the complete cohort. Age, plasma miR-106-5p, miR-486-5p, SP-D protein levels, and SP-D mRNA level were also determined to be correlated with FEV1%Pred, and may as the risk factors of Tibetan COPD. The combination of plasma miR-106-5p, miR-486-5p and SP-D mRNA expression may be the best model to assist the diagnosis of Tibetan COPD.
Asunto(s)
MicroARN Circulante , MicroARNs , Enfermedad Pulmonar Obstructiva Crónica , Proteína D Asociada a Surfactante Pulmonar , MicroARN Circulante/sangre , Perfilación de la Expresión Génica , Humanos , MicroARNs/genética , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/genética , Proteína D Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/genética , ARN Mensajero , TibetRESUMEN
BACKGROUND: Surfactant Protein D (SP-D) is a pattern recognition molecule belonging to the family of collectins expressed in multiple human organ systems, including the lungs. Previous studies have shown that SP-D levels in bronchoalveolar lavage samples decrease and serum levels increase in patients suffering from asthma, possibly due to a combination of induced SP-D synthesis and decreased air-blood barrier integrity. The aims of this study were to investigate whether serum levels of SP-D and common variants in the SP-D gene were associated with asthma in adolescents and young adults. METHODS: Prospective observational study including 449 adolescents and young adults (age 11-27 years) previously diagnosed with asthma during a 2-year period from 2003 to 2005 (0-16 years). At follow-up from 2016 to 2017, 314 healthy controls with no history of asthma were recruited. Serum SP-D was analyzed on samples obtained at baseline as well as samples obtained at follow-up. SP-D genotyping was performed for rs721917, rs2243639, and rs3088308. RESULTS: No differences were found in mean levels of sSP-D and SFTPD genotype among subjects with current asthma, no current asthma, and controls. Serum SP-D and SFTPD genotype were not associated with any clinical parameters of asthma. Furthermore, baseline sSP-D was not associated with asthma at follow-up. CONCLUSION: Serum surfactant protein D and common SP-D gene variants were not associated with asthma in Danish adolescents and young adults with mild to moderate asthma. Serum surfactant protein D did not demonstrate any value as a clinical biomarker of asthma.
Asunto(s)
Asma , Proteína D Asociada a Surfactante Pulmonar , Adolescente , Adulto , Asma/genética , Niño , Dinamarca/epidemiología , Genotipo , Humanos , Pulmón , Proteína D Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/genética , Adulto JovenRESUMEN
To evaluate the effect of liraglutide, a glucagon-like peptide 1 receptor agonist, on pulmonary function and serum levels of surfactant protein D (SP-D) in type 2 diabetes. A double-blind, randomized, crossover, placebo-controlled clinical trial comprising 76 patients with a baseline forced expiratory volume in 1 s <90% of that predicted. Liraglutide was administered for 7 weeks (2 weeks of titration plus 5 weeks at 1.8 mg daily). This short duration was intentional to minimize weight loss as a potential confounding factor. Serum level of SP-D was used as a biomarker of alveolar-capillary barrier integrity. Liraglutide exerted a positive impact on forced vital capacity (FVC) in comparison with placebo (ΔFVC 5.2% of predicted [from 0.8 to 9.6]; P = 0.009). No differences in the other pulmonary variables were observed. Participants under liraglutide treatment also experienced a decrease in serum SP-D (P = 0.038). The absolute change in FVC correlated with final serum SP-D in participants receiving liraglutide (r = -0.313, P = 0.036). Stepwise multivariate regression analysis showed that final serum SP-D independently predicted changes in FVC. In conclusion, liraglutide increased FVC in patients with type 2 diabetes. This effect was associated with a significant decrease of circulating SP-D, thus pointing to a beneficial effect in the alveolar-capillary function.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Liraglutida/uso terapéutico , Pulmón/efectos de los fármacos , Anciano , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Estudios Cruzados , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Método Doble Ciego , Femenino , Control Glucémico , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Proteína D Asociada a Surfactante Pulmonar/sangre , España , Capacidad Vital/efectos de los fármacosRESUMEN
PURPOSE: The degree of silicosis exposure is closely related to the progress of silicosis. At present, we use animal and human studies to explore whether silicon can be an important exposure marker in the development of silicosis. METHODS: Rats were randomly divided into 2 groups: (1) controls; and (2) silicosis. Rats in the silicosis group were killed at 4, 8, 12, 16, 24 h, 3, 7, 14, 21, and 28 days. Hematoxylin-eosin (HE) and immunohistochemistry (IHC) were performed to observe the histomorphology of lung tissue. The expression levels of CC16 and SP-D were detected using ELISA kits. In addition, we conducted a population study. Workers who have been selected to work in an iron mine for more than 1 year as research objects. The population was divided into four groups: silicosis exposure group (workers exposed to silica dust for more than 1 year in an iron mine were selected); patients group (silicosis patients); observation group (evidence of disease not meeting formal diagnostic criteria) and control group. Both the levels of trace silicon in the urine and blood of rats and human subjects were measured with ICP-MS. RESULTS: Serum levels of silicon were immediately increased in rats exposed to silicon dust. Similarly, our population study revealed that the silicon level in the silica exposure group and the observing group (exposed but no obvious symptoms) were significantly increased over that of the control group (P < 0.05). In subjects with extended exposure to silica, the serum and urine silicon level in exposed workers appeared to rapidly increase, reaching its peak in 1-5 years, followed by a gradual decline thereafter. Workers exposed to dust for less than 10 years were divided into subgroups by 2-year limit. The levels of serum silicon, urine silicon, TGF-ß1, and TNF-α were significantly higher than that of control group. CONCLUSION: Changes of the serum levels of silicon occurred earlier than the expression of cytokines such as TNF-α, TGF-ß1, CC16, and SP-D. The level of silicon in workers rapidly increased after exposure to silica, and the change occurred before the expression of TGF-ß1 and TNF-α. As a whole, the findings suggest that determining the level of silicon in vivo might be an effective exposure marker in the diagnosis and pathogenesis of silicosis.
Asunto(s)
Exposición por Inhalación , Exposición Profesional , Silicio/sangre , Silicosis/sangre , Factor de Crecimiento Transformador beta1/sangre , Factor de Necrosis Tumoral alfa/sangre , Administración por Inhalación , Adulto , Anciano , Animales , Humanos , Hierro , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Masculino , Persona de Mediana Edad , Minería , Proteína D Asociada a Surfactante Pulmonar/sangre , Ratas Wistar , Silicio/orina , Dióxido de Silicio/administración & dosificación , Silicosis/diagnóstico , Silicosis/inmunología , Factor de Crecimiento Transformador beta1/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Uteroglobina/sangreAsunto(s)
Angiopoyetina 2/sangre , COVID-19/sangre , Productos Finales de Glicación Avanzada/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Síndrome de Dificultad Respiratoria/sangre , Adulto , Anciano , Biomarcadores/sangre , COVID-19/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Dificultad Respiratoria/etiología , Estudios Retrospectivos , Factores de TiempoRESUMEN
BLAST searches against databases for the bullfrog (Rana catesbeiana), using the collectin sequence previously identified in tadpoles, revealed the presence of at least 20 members of the collectin gene family. Phylogenetic analysis demonstrated that the bullfrog possesses expanded gene subfamilies encoding mannose-binding lectin (MBL) and pulmonary surfactant-associated protein D (PSAPD). Two collectins, of 20 kDa (PSAPD1) and 25 kDa (PSAPD6), were purified as a mixture from adult bullfrog plasma using affinity chromatography. These collectins were present as an oligomer of ~400 kDa in their native state, and showed Ca2+-dependent carbohydrate binding with different sugar preferences. Affinity-purified collectins showed weak E. coli agglutination and bactericidal activities, compared with those of plasma. Although both PSAPD1 and PSAPD6 genes were predominantly expressed in the liver, PSAPD1 transcripts were abundant in adults whereas PSAPD6 transcripts were abundant in tadpoles. The findings indicate that two gene subfamilies in the collectin family have diverged structurally, functionally and transcriptionally in the bullfrog. Rapid expansion of the collectin family in bullfrogs may reflect the onset of sub-functionalization of the prototype MBL gene towards tetrapod MBL and PSAPDs, and may be one means of natural adaptation in the innate immune system to various pathogens in both aquatic and terrestrial environments.
Asunto(s)
Carbohidratos/inmunología , Inmunidad Innata/inmunología , Lectina de Unión a Manosa/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Rana catesbeiana/metabolismo , Aglutinación/inmunología , Animales , Adhesión Bacteriana/inmunología , Metabolismo de los Hidratos de Carbono/inmunología , Colectinas/sangre , Colectinas/genética , Colectinas/metabolismo , Escherichia coli/inmunología , Inmunidad Innata/genética , Larva/inmunología , Lectina de Unión a Manosa/genética , Lectina de Unión a Manosa/metabolismo , Filogenia , Proteína D Asociada a Surfactante Pulmonar/genética , Proteína D Asociada a Surfactante Pulmonar/metabolismoRESUMEN
This work studies the relationship between lung inflammation caused by nanomaterials and surfactant protein D (SP-D) kinetics and investigates whether SP-D can be a biomarker of the pulmonary toxicity of nanomaterials. Nanomaterials of nickel oxide and cerium dioxide were classified as having high toxicity, nanomaterials of two types of titanium dioxides and zinc oxide were classified as having low toxicity, and rat biological samples obtained from 3 days to 6 months after intratracheal instillation of those nanomaterials and micron-particles of crystalline silica were used. There were different tendencies of increase between the high- and low-toxicity materials in the concentration of SP-D in bronchoalveolar-lavage fluid (BALF) and serum and in the expression of the SP-D gene in the lung tissue. An analysis of the receiver operating characteristics for the toxicity of the nanomaterials by SP-D in BALF and serum showed a high accuracy of discrimination from 1 week to 3 or 6 months after exposure. These data suggest that the differences in the expression of SP-D in BALF and serum depended on the level of lung inflammation caused by the nanomaterials and that SP-D can be biomarkers for evaluating the pulmonary toxicity of nanomaterials.
Asunto(s)
Pulmón/efectos de los fármacos , Nanoestructuras/toxicidad , Proteína D Asociada a Surfactante Pulmonar/sangre , Pruebas de Toxicidad/normas , Animales , Biomarcadores/sangre , Líquido del Lavado Bronquioalveolar/química , Pulmón/metabolismo , Masculino , Nanoestructuras/administración & dosificación , Ratas Endogámicas F344 , Pruebas de Toxicidad/métodosRESUMEN
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.
Asunto(s)
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 lambdaRESUMEN
Pulmonary surfactant protein D (SP-D) is an important component of the pulmonary innate immune system with the ability to dampen cigarette smoke-induced lung inflammation. However, cigarette smoking mediates translocation of SP-D from the lung to the blood, and serum SP-D (sSP-D) has therefore previously been suggested as marker for smoke-induced lung injury. In support of this notion, associations between high sSP-D and low lung function measurements have previously been demonstrated in smokers and in chronic obstructive lung disease (COPD). The present investigations employ a 12-yr longitudinal Danish twin study to test the hypothesis that baseline sSP-D variation has the capacity to identify smokers with normal baseline lung function who are at high risk of significant future smoke-induced lung function decline. We find that sSP-D is significantly increased in those with normal lung function at baseline who develop lung function decline during follow-up compared with those who stay lung healthy. Moreover, we demonstrate that it is the smoke-induced baseline sSP-D level, and not the constitutional level, which has capacity as biomarker, and which is linearly increased with the decline in lung function during follow-up. In conclusion, we here present first observation of increased sSP-D for identification of high-risk smokers.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Proteína D Asociada a Surfactante Pulmonar/sangre , Humo/efectos adversos , Biomarcadores/metabolismo , Líquido del Lavado Bronquioalveolar , Humanos , Pulmón/metabolismo , Pulmón/fisiopatología , Riesgo , Fumar/metabolismoRESUMEN
The differentiation between influenza and coronavirus disease 2019 (COVID-19) could constitute a diagnostic challenge during the ongoing winter owing to their clinical similitude. Thus, novel biomarkers are required to enable making this distinction. Here, we evaluated whether the surfactant protein D (SP-D), a collectin produced at the alveolar epithelium with known immune properties, was useful to differentiate pandemic influenza A(H1N1) from COVID-19 in critically ill patients. Our results revealed high serum SP-D levels in patients with severe pandemic influenza but not those with COVID-19. This finding was validated in a separate cohort of mechanically ventilated patients with COVID-19 who also showed low plasma SP-D levels. However, plasma SP-D levels did not distinguish seasonal influenza from COVID-19 in mild-to-moderate disease. Finally, we found that high serum SP-D levels were associated with death and renal failure among severe pandemic influenza cases. Thus, our studies have identified SP-D as a unique biomarker expressed during severe pandemic influenza but not COVID-19.
Asunto(s)
COVID-19/genética , Expresión Génica , Interacciones Huésped-Patógeno/genética , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/genética , Proteína D Asociada a Surfactante Pulmonar/genética , SARS-CoV-2 , Adulto , Anciano , Biomarcadores , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/virología , Coinfección , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Gripe Humana/diagnóstico , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Pronóstico , Proteína D Asociada a Surfactante Pulmonar/sangre , Índice de Severidad de la Enfermedad , Evaluación de Síntomas , Adulto JovenRESUMEN
Damage-associated molecular patterns (DAMPs) have drawn much attention as a member of disease-associated molecules in systemic sclerosis (SSc). In this study, we investigated the potential contribution of S100A12, a member of DAMPs, to the development of SSc by evaluating S100A12 expression in the lesional skin and the clinical correlation of serum S100A12 levels. S100A12 expression was markedly elevated in the epidermis of SSc-involved skin at protein levels and in the bulk skin at mRNA levels. The deficiency of transcription factor Fli1, a predisposing factor of SSc, enhanced S100A12 expression and Fli1 occupied the S100A12 promoter in normal human keratinocytes. Serum S100A12 levels were higher in SSc patients, especially in those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, the presence of interstitial lung disease significantly augmented serum levels of S100A12. Importantly, serum S100A12 levels correlated inversely with both per cent forced vital capacity and per cent diffusing capacity for carbon monoxide and positively with serum levels of KL-6 and surfactant protein-D. Collectively, these results indicate a possible contribution of S100A12 to skin sclerosis and interstitial lung disease associated with SSc, further supporting the critical roles of DAMPs in the pathogenesis of this disease.
Asunto(s)
Enfermedades Pulmonares Intersticiales/sangre , Proteína S100A12/sangre , Esclerodermia Sistémica/sangre , Estudios de Casos y Controles , Epidermis/metabolismo , Humanos , Queratinocitos , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/fisiopatología , Mucina-1/sangre , Proteína Proto-Oncogénica c-fli-1/genética , Proteína Proto-Oncogénica c-fli-1/metabolismo , Capacidad de Difusión Pulmonar , Proteína D Asociada a Surfactante Pulmonar/sangre , ARN Mensajero/metabolismo , Proteína S100A12/genética , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/genética , Esclerodermia Sistémica/metabolismo , Índice de Severidad de la Enfermedad , Capacidad VitalRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the antifibrotic drug pirfenidone. METHODS: We conducted a post-hoc analysis of the prospective, multicenter, randomized, placebo-controlled, phase 3 trial of pirfenidone in Japan (total, n = 267; pirfenidone, n = 163; placebo, n = 104). Logistic regression analysis was performed to extract parameters that predicted disease progression, defined by a ≥ 10% relative decline in vital capacity (VC) from baseline and/or death, at week 52. For assessment of serum surfactant protein (SP)-D, SP-A and Krebs von den Lungen (KL)-6, all patients were dichotomized by the median concentration of each biomarker at baseline to the high and low biomarker subgroups. Associations of these concentrations were examined with changes in VC at each time point from baseline up to week 52, along with progression-free survival (PFS). Additionally, the effect of pirfenidone treatment on serial longitudinal concentrations of these biomarkers were evaluated. RESULTS: In the multivariate logistic regression analysis, body mass index (BMI), %VC and SP-D in the pirfenidone group, and BMI and %VC in the placebo group were indicated as predictors of disease progression. Pirfenidone treatment reduced the decline in VC with statistical significance in the low SP-D and low SP-A subgroups over most of the treatment period, and also prolonged PFS in the low SP-D and low KL-6 subgroups. Furthermore, SP-D levels over time course were reduced in the pirfenidone group from as early as week 8 until the 52-week treatment period compared with the placebo group. CONCLUSIONS: Serum SP-D was the most consistent biomarker for the efficacy of pirfenidone in the cohort trial of IPF. Serial measurements of SP-D might have a potential for application as a pharmacodynamic biomarker. Trial registration The clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13, 2005 (registration No. JapicCTI-050121; http://Clinicaltrials.jp ).
Asunto(s)
Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Pulmón/efectos de los fármacos , Proteína D Asociada a Surfactante Pulmonar/sangre , Piridonas/uso terapéutico , Anciano , Biomarcadores/sangre , Índice de Masa Corporal , Método Doble Ciego , Femenino , Humanos , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/fisiopatología , Pulmón/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Piridonas/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Capacidad VitalRESUMEN
PURPOSE: SARS-CoV-2 (COVID-19) has infected more than 7 million people worldwide in the short time since it emerged in Wuhan, China in December 2019. The aim of this study was to investigate the relationship between serum interleukin 6 (IL-6) and surfactant protein D (SP-D) levels and the clinical course and prognosis of COVID-19. MATERIALS AND METHODS: The study included a total of 108 individuals: 88 patients who were diagnosed with COVID-19 by real-time PCR of nasopharyngeal swab samples and admitted to the Atatürk University Pulmonary Diseases and the Erzurum City Hospital Infectious Diseases department between March 24 and April 15, and 20 asymptomatic healthcare workers who had negative real-time PCR results during routine COVID-19 screening in our hospital. RESULTS: Patients who developed macrophage activation syndrome had significantly higher IL-6 and SP-D levels at the time of admission and on day 5 of treatment compared to the other patients (IL-6: p = 0.001 for both; SP-D: p = 0.02, p = 0.04). Patients who developed acute respiratory distress syndrome had significantly higher IL-6 and SP-D levels at both time points compared to those who did not (p = 0.001 for all). Both parameters at the time of admission were also significantly higher among nonsurvivors compared to survivors (IL-6: p = 0.001, SP-D: p = 0.03). CONCLUSION: In addition to IL-6, which has an important role in predicting course and planning treatment in COVID-19, SP-D may be a novel pneumoprotein that can be used in the clinical course, follow-up, and possibly in future treatments.