RESUMEN
BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been associated with increased risks of respiratory diseases, but the biological mechanisms are not yet fully elucidated. OBJECTIVES: Our aim was to evaluate the respiratory responses and explore potential biological mechanisms of TRAP exposure in a randomized crossover trial. METHODS: We conducted a randomized crossover trial in 56 healthy adults. Each participant was exposed to high- and low-TRAP exposure sessions by walking in a park and down a road with high traffic volume for 4 h in random order. Respiratory symptoms and lung function, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), the ratio of FEV1 to FVC, and maximal mid-expiratory flow (MMEF), were measured before and after each exposure session. Markers of 8-isoprostane, tumor necrosis factor-α (TNF-α), and ezrin in exhaled breath condensate (EBC), and surfactant proteins D (SP-D) in serum were also measured. We used linear mixed-effects models to estimate the associations, adjusted for age, sex, body mass index, meteorological condition, and batch (only for biomarkers). Liquid chromatography-mass spectrometry was used to profile the EBC metabolome. Untargeted metabolome-wide association study (MWAS) analysis and pathway enrichment analysis using mummichog were performed to identify critical metabolomic features and pathways associated with TRAP exposure. RESULTS: Participants had two to three times higher exposure to traffic-related air pollutants except for fine particulate matter while walking along the road compared with in the park. Compared with the low-TRAP exposure at the park, high-TRAP exposure at the road was associated with a higher score of respiratory symptoms [2.615 (95% CI: 0.605, 4.626), p=1.2×10-2] and relatively lower lung function indicators [-0.075L (95% CI: -0.138, -0.012), p=2.1×10-2] for FEV1 and -0.190L/s (95% CI: -0.351, -0.029; p=2.4×10-2) for MMEF]. Exposure to TRAP was significantly associated with changes in some, but not all, biomarkers, particularly with a 0.494-ng/mL (95% CI: 0.297, 0.691; p=9.5×10-6) increase for serum SP-D and a 0.123-ng/mL (95% CI: -0.208, -0.037; p=7.2×10-3) decrease for EBC ezrin. Untargeted MWAS analysis revealed that elevated TRAP exposure was significantly associated with perturbations in 23 and 32 metabolic pathways under positive- and negative-ion modes, respectively. These pathways were most related to inflammatory response, oxidative stress, and energy use metabolism. CONCLUSIONS: This study suggests that TRAP exposure might lead to lung function impairment and respiratory symptoms. Possible underlying mechanisms include lung epithelial injury, inflammation, oxidative stress, and energy metabolism disorders. https://doi.org/10.1289/EHP11139.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Adulto , Humanos , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Exposición a Riesgos Ambientales/análisis , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Material Particulado/toxicidad , Material Particulado/análisis , Emisiones de Vehículos/toxicidad , Emisiones de Vehículos/análisis , Biomarcadores/análisis , Metaboloma , PulmónRESUMEN
Purpose: Pulmonary surfactant proteins A (SP-A) and D (SP-D) are lectins, involved in host defense and regulation of pulmonary inflammatory response. However, studies on the assessment of COPD progress are limited. Patients and Methods: Pulmonary surfactant proteins were obtained from the COPD mouse model induced by cigarette and lipopolysaccharide, and the specimens of peripheral blood and bronchoalveolar lavage (BALF) in COPD populations. H&E staining and RT-PCR were performed to demonstrate the successfully established of the mouse model. The expression of SP-A and SP-D in mice was detected by Western Blot and immunohistochemistry, while the proteins in human samples were measured by ELISA. Pulmonary function test, inflammatory factors (CRP, WBC, NLR, PCT, EOS, PLT), dyspnea index score (mMRC and CAT), length of hospital stay, incidence of complications and ventilator use were collected to assess airway remodeling and progression of COPD. Results: COPD model mice with emphysema and airway wall thickening were more prone to have decreased SP-A, SP-D and increased TNF-α, TGF-ß, and NF-kb in lung tissue. In humans, SP-A and SP-D decreased in BALF, but increased in serum. The serum SP-A and SP-D were negatively correlated with FVC, FEV1, FEV1/FVC, and positively correlated with CRP, WBC, NLR, mMRC and CAT scores (P < 0.05, respectively). The lower the SP-A and SP-D in BALF, the worse the lung function and the increased probability of complications and ventilator use. Moreover, the same trend emerged in COPD patients grouped according to GOLD severity grade (Gold 1-2 group vs Gold 3-4 group). The worse the patient's condition, the more pronounced the change. Conclusion: This study suggests that SP-A and SP-D may be related to the progression and prognostic evaluation of COPD in terms of airway remodeling, inflammatory response and clinical symptoms, and emphasizes the necessity of future studies of surfactant protein markers in COPD.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Surfactantes Pulmonares , Remodelación de las Vías Aéreas (Respiratorias) , Animales , Biomarcadores , Ratones , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Proteína A Asociada a Surfactante Pulmonar/uso terapéutico , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/uso terapéutico , Surfactantes Pulmonares/uso terapéuticoRESUMEN
BACKGROUND: Surfactant proteins (SP) A and D belong to collectin family proteins, which play important roles in innate immune response in the lung. We previously demonstrated that cigarette smoke (CS) increases the acrolein modification of SP-A, thereby impairing the innate immune abilities of this protein. In this study, we focused on the effects of CS and its component, acrolein, on the innate immunity role of another collectin, SP-D. METHODS: To determine whether aldehyde directly affects SP-D, we examined the lungs of mice exposed to CS for 1 week and detected aldehyde-modified SP-D using an aldehyde reactive probe. The structural changes in CS extract (CSE) or acrolein-exposed recombinant human (h)SP-D were determined by western blot, liquid chromatography-electrospray ionization tandem mass spectrometry, and blue native-polyacrylamide gel electrophoresis analyses. Innate immune functions of SP-D were determined by bacteria growth and macrophage phagocytosis. RESULTS: Aldehyde-modified SP-D as well as SP-A was detected in the lungs of mice exposed to CS for 1 week. Exposure of hSP-D to CSE or acrolein induced an increased higher-molecular -weight of hSP-D and acrolein induced modification of five lysine residues in hSP-D. These modifications led to disruption of the multimer structure of SP-D and attenuated its ability to inhibit bacterial growth and activate macrophage phagocytosis. CONCLUSION: CS induced acrolein modification in SP-D, which in turn induced structural and functional defects in SP-D. GENERAL SIGNIFICANCE: These results suggest that CS-induced structural and functional defects in SP-D contribute to the dysfunction of innate immune responses in the lung following CS exposure.
Asunto(s)
Acroleína/efectos adversos , Inmunidad Innata , Pulmón/inmunología , Proteína D Asociada a Surfactante Pulmonar/inmunología , Humo/efectos adversos , Fumar Tabaco/efectos adversos , Acroleína/análisis , Animales , Femenino , Humanos , Inmunidad Innata/efectos de los fármacos , Pulmón/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Fagocitosis/efectos de los fármacos , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteínas Recombinantes/análisis , Proteínas Recombinantes/inmunología , Humo/análisis , Nicotiana/química , Fumar Tabaco/inmunologíaRESUMEN
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
BACKGROUND: Acute lung injury (ALI) is a frequent complication after severe trauma. Lung-protective ventilation strategies and damage control resuscitation have been proposed for the prevention of ALI; however, there are no clinical or laboratory parameters to predict who is at risk of developing ALI after trauma. In the present study, we explored pulmonary inflammatory markers as a potential predictor of ALI using a porcine model of hemorrhagic shock. MATERIALS AND METHODS: Female swine were randomized to mechanical ventilation with low tidal volume (VT) (6 mL/kg) or high VT (12 mL/kg). After equilibration, animals underwent pressure-controlled hemorrhage (mean arterial pressure [MAP] 35 ± 5 mmHg) for 1 h, followed by resuscitation with fresh whole blood or Hextend. They were maintained at MAP of 50 ± 5 mmHg for 3 h in the postresuscitation phase. Bronchoalveolar lavage fluids were collected hourly and analyzed for inflammatory markers. Lung samples were taken, and porcine neutrophil antibody staining was used to evaluate the presence of neutrophils. ELISA evaluated serum porcine surfactant protein D levels. Sham animals were used as negative controls. RESULTS: Pigs that underwent hemorrhagic shock had higher heart rates, lower cardiac output, lower MAPs, and worse acidosis compared with sham at the early time points (P < 0.05 each). There were no significant differences in central venous pressure or pulmonary capillary wedge pressure between groups. Pulmonary neutrophil infiltration, as defined by neutrophil antibody staining on lung samples, was greater in the shock groups regardless of resuscitation fluid (P < 0.05 each). Bronchoalveolar lavage fluid neutrophil levels were not different between groups. There were no differences in levels of porcine surfactant protein D between groups at any time points, and the levels did not change over time in each respective group. CONCLUSIONS: Our study demonstrates the reproducibility of a porcine model of hemorrhagic shock that is consistent with physiologic changes in humans in hemorrhagic shock. Pulmonary neutrophil infiltration may serve as an early marker for ALI; however, the practicality of this finding has yet to be determined.
Asunto(s)
Lesión Pulmonar Aguda/diagnóstico , Neutrófilos/inmunología , Choque Hemorrágico/complicaciones , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/fisiopatología , Lesión Pulmonar Aguda/prevención & control , Animales , Transfusión Sanguínea , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Gasto Cardíaco/inmunología , Modelos Animales de Enfermedad , Femenino , Frecuencia Cardíaca/inmunología , Humanos , Pulmón/citología , Pulmón/inmunología , Pulmón/patología , Infiltración Neutrófila , Valor Predictivo de las Pruebas , Pronóstico , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/inmunología , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Reproducibilidad de los Resultados , Respiración Artificial/instrumentación , Respiración Artificial/métodos , Resucitación/métodos , Choque Hemorrágico/inmunología , Choque Hemorrágico/terapia , Sus scrofa , Factores de TiempoRESUMEN
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.
Asunto(s)
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
The article reveals the modern aspects of IPF pathogenesis in with an emphasis on the main proposed prognostic biomarkers. IPF remains the leader among diseases with unknown etiology, the diagnosis and management of which are not very successful, despite the obvious progress in molecular medicine. There is presented analysis of the significance of IPF potential biomarkers and their concentrations in the blood and bronchoalveolar lavage fluids (BAL): endothelin-1, CC-chemokine ligand 18, interleukin-1, surfactant protein SP-D in the review. The role of their changing levels in the blood and BAL for assessing the course of the IPF and its prognosis, as well as the prevailing importance of the polymorphism of the genes encoding them, is shown. Obviously, the progressive accumulation of fibroblast-myofibroblast cells in the lungs IPF patients worsens the prognosis of disease, forms its own environment with a set of cytokines, growth factors, collagen, fibronectin in the extracellular matrix of fibrous lungs. The insufficient amount of studies in the face of the rarity of the disease leaves a lot of controversial issues for solution in the future. Obviously, to assess the prognosis of IPF mortality, it is necessary to include a very large number of patients, to extend the observation period, which increases their cost and reduces the opportunities and desire of pharmaceutical companies to participate in these studies.
Asunto(s)
Biomarcadores/sangre , Líquido del Lavado Bronquioalveolar/química , Fibrosis Pulmonar Idiopática/diagnóstico , Pulmón/metabolismo , Biomarcadores/análisis , Quimiocinas CC , Endotelina-1 , Humanos , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/mortalidad , Interleucina-1 , Pulmón/fisiopatología , Pronóstico , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/sangre , Surfactantes Pulmonares/análisis , Surfactantes Pulmonares/sangreRESUMEN
OBJECTIVE: Asphyxia of newborns is a severe and frequent challenge of the peri- and postnatal period. The purpose of this study was to study early morphological, immunological and structural alterations in lung tissue after asphyxia and hemorrhage (AH). METHODS: 44 neonatal piglets (age 32 hrs) underwent asphyxia and hemorrhage (AH) and were treated according to the international liaison committee of resuscitation (ILCOR) guidelines. For this study, 15 piglets (blood transfusion (RBC) n = 9; NaCl n = 6, mean age 31 hrs) were randomly picked. 4 hours after ROSC (return of spontaneous circulation), lung tissue and blood samples were collected. RESULTS: An elevation of myeloperoxidase (MPO) activity was observed 4 hrs after AH accompanied by an increase of surfactant D after RBC treatment. After AH tight junction proteins Claudin 18 and junctional adhesion molecule 1 (JAM1) were down-regulated, whereas Occludin was increased. Furthermore, after AH and RBC treatment dephosphorylated active form of Connexin 43 was increased. CONCLUSIONS: AH in neonatal pigs is associated with early lung injury, inflammation and alterations of tight junctions (Claudin, Occludin, JAM-1) and gap junctions (Connexin 43) in lung tissue, which contributes to the development of lung edema and impaired function.
Asunto(s)
Asfixia Neonatal/fisiopatología , Lesión Pulmonar/fisiopatología , Pulmón/fisiopatología , Animales , Animales Recién Nacidos/metabolismo , Asfixia/fisiopatología , Asfixia Neonatal/metabolismo , Moléculas de Adhesión Celular/metabolismo , Claudinas/metabolismo , Conexina 43/metabolismo , Modelos Animales de Enfermedad , Uniones Comunicantes , Lesión Pulmonar/metabolismo , Ocludina/metabolismo , Peroxidasa/análisis , Proteína D Asociada a Surfactante Pulmonar/análisis , Choque Hemorrágico/inmunología , Choque Hemorrágico/metabolismo , Porcinos , Uniones Estrechas/metabolismoRESUMEN
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.
Asunto(s)
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
BACKGROUND: The purpose of this study is to investigate whether airborne exposure to endotoxins, hydrogen sulphide (H2S), and inhalable particles negatively impacts the respiratory system and inflammatory blood proteins in sewage plant and sewer net system workers and, further, to determine dose-response associations between exposure and health outcomes. METHODS: In total, 148 waste water workers (WWWs) from urban and rural sewage plants and the sewer net system participated. One hundred and twenty-one workers were exposed to sewage, 46 from sewage plants and 75 from the sewer net system. Twenty-seven workers were characterized as little or not exposed and served as an internal reference group. Personal inhalable samples were analysed for endotoxins (Limulus assay), particle dust (gravimetrically) and Salmonella and Yersinia spp. (polymerase chain reaction method, PCR). Levels of H2S were measured using personal electro chemical sensors. Intercellular adhesion molecule 1 (ICAM-1), interleukin 8 (IL-8), surfactant protein D (SP-D), club cell protein 16 (CC16), and macrophage inflammatory protein (MIP) were determined by enzyme-linked immunosorbent assay and C-reactive protein (CRP) by an HS-MicroCRP assay in blood samples. RESULTS: Workers in sewage plants were exposed to significantly higher levels of endotoxins compared to workers in the sewer net system [median 55 EU m-3 (4-262 EU m-3) and median 27 EU m-3 (1-304 EU m-3), respectively]. The estimated H2S index showed higher values when working in the sewer net system [median 3.1 (0.5-78.1)] compared to workers at the sewage plants [median 1.3 (0.5-9.3)], and the most excessive exposure was collecting sewage from cesspools (273 p.p.m.). No viable airborne Salmonella and Yersinia spp. were detected. The exposed workers had significantly higher CRP compared to the referents [1.2 µg ml-1 (0.1-19.0 µg ml-1) and 0.8 µg ml-1 (0.1-5.0 µg ml-1), respectively] and lower forced expiratory volume in 1 s (FEV1)% [92.6%, standard deviation (SD) 14.6 and 102.0%, SD 10.1, respectively], with numbers given as mean and SD. The serum concentration of CRP was significantly and negatively associated with FEV1% (ß = -7.7, R2 = 0.05) and forced vital capacity % (ß = -8.5, R2 = 0.08), and the serum concentration of ICAM-1 with the estimated exposure to H2S (ß = -19.9, R2 = 0.07). CONCLUSION: Despite moderate levels of endotoxin and H2S exposure, the results indicate an impact of these agents on lung function and the adhesion molecule ICAM-1, and a low-grade systemic inflammation was indicated in increased levels of CRP.
Asunto(s)
Endotoxinas/efectos adversos , Sulfuro de Hidrógeno/efectos adversos , Enfermedades Profesionales/etiología , Exposición Profesional/análisis , Trastornos Respiratorios/inducido químicamente , Aguas del Alcantarillado , Aguas Residuales , Adulto , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Polvo/análisis , Endotoxinas/análisis , Femenino , Humanos , Sulfuro de Hidrógeno/análisis , Molécula 1 de Adhesión Intercelular/análisis , Interleucina-8/análisis , Masculino , Persona de Mediana Edad , Proteína D Asociada a Surfactante Pulmonar/análisis , Sistema Respiratorio/metabolismoRESUMEN
Chronic obstructive pulmonary disease (COPD) is a progressive disease underlain by airway inflammation. Despite trials with new generations of anti-inflammatory drugs to alleviate the disease burden, the effective curative treatment remains elusive. In this context, the aim of this study was to assess the influence of simvastatin, a leading member of the family of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known to display anti-inflammatory and immunomodulatory activity, on symptoms and lung function, as well as the proportion of inflammatory cells, cytokines, proteolytic enzymes, and surfactant protein D (SP-D) content in bronchoalveolar lavage fluid (BALF) in COPD patients. There were 50 patients with moderate-to-severe airway obstructions included into the study, subdivided into simvastatin-treated (Zocor - MSD; 40 mg daily) and control simvastatin-untreated groups, other treatment being equal. Pulmonary functions tests and bronchofiberoscopy with BALF procedure were performed before and after 3-month-long treatment in both groups. The major finding was that simvastatin treatment caused a distinct increase in the airway content of SP-D. Further effects, albeit smaller in magnitude, consisted of reductions in the proportion of airway neutrophils and in MMP-9 content, all with a benefit of improved score in the disease activity assessment test. There were no appreciable changes noted in lung function or dyspnea perception, which could be ascribed to simvastatin treatment. We conclude that statin's anti-inflammatory and surfactant homeostasis preserving properties may offer promise as an adjunctive treatment in COPD patients. The SP-D content in BALF has a potential to become a marker of COPD inflammatory activity and treatment monitoring.
Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Proteína D Asociada a Surfactante Pulmonar/análisis , Simvastatina/uso terapéutico , Antiinflamatorios/administración & dosificación , Biomarcadores/metabolismo , Humanos , Pulmón , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Biomarcadores/sangre , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/genética , Autoanticuerpos/análisis , Autoanticuerpos/sangre , Biomarcadores/análisis , Líquido del Lavado Bronquioalveolar/química , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/sangre , Quimiocina CXCL13/análisis , Quimiocina CXCL13/sangre , Quimiocinas CC/análisis , Quimiocinas CC/sangre , Progresión de la Enfermedad , Proteínas HSP70 de Choque Térmico/inmunología , Humanos , Japón , Metaloproteinasas de la Matriz/análisis , Metaloproteinasas de la Matriz/sangre , Mucina-1/análisis , Mucina-1/sangre , Valor Predictivo de las Pruebas , Pronóstico , 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 , Esputo/química , alfa-Defensinas/análisis , alfa-Defensinas/sangreRESUMEN
Surfactant proteins in different glandular structures of the oral cavity display antimicrobial activity for protection of invading microorganisms. Moreover, they are involved in lowering liquid tension in fluids and facilitate secretion flows. Numerous investigations for studying the occurrence of surfactant proteins in glandular tissues were performed using different methods. In the oral cavity, minor salivary glands secrete saliva continuously for the maintenance of a healthy oral environment. For the first time, we could show that infantile labial glands show expression of the surfactant proteins (SP) SP-A, SP-B, SP-C, and SP-D in acinar cells and the duct system in different intensities. The stratified squamous epithelium of the oral mucosa revealed positive staining for SPs in various cell layers.
Asunto(s)
Proteína A Asociada a Surfactante Pulmonar/análisis , Proteína B Asociada a Surfactante Pulmonar/análisis , Proteína C Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/análisis , Glándulas Salivales Menores/ultraestructura , Preescolar , Femenino , Humanos , Inmunohistoquímica/métodos , Lactante , Masculino , Mucosa Bucal/química , Mucosa Bucal/ultraestructura , Glándulas Salivales Menores/químicaRESUMEN
BACKGROUND: Neuromuscular blockade (NMB) is a therapy for acute respiratory distress syndrome (ARDS). However, the mechanism by which NMB may improve outcome for ARDS patients remains unclear. We sought to determine whether NMB attenuates biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients, and whether the association is dependent on tidal volume size and the initial degree of hypoxemia. METHODS: We performed a secondary analysis of patients enrolled in the ARDS network low tidal volume ventilation (ARMA) study. Our primary predictor variable was the number of days receiving NMB between study enrollment and day 3. Our primary outcome variables were the change in concentration of biomarkers of epithelial injury (serum surfactant protein-D (SP-D)), endothelial injury (von Willebrand factor (VWF)), and systemic inflammation (interleukin (IL)-8). Multivariable regression analysis was used to compare the change in biomarker concentration controlling for multiple covariates. Patients were stratified by treatment arm (12 versus 6 cm3/kg) and by an initial arterial oxygen tension (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio of 120. RESULTS: A total of 446 (49%) patients had complete SP-D, VWF, and IL-8 measurements on study enrollment and day 3. After adjusting for baseline differences, each day of NMB was associated with a decrease in SP-D (-23.7 ng/ml/day, p = 0.029), VWF (-33.5% of control/day, p = 0.015), and IL-8 (-362.6 pg/ml/day, p = 0.030) in patients with an initial P/F less than or equal to 120 and receiving low tidal volume ventilation. However, patients with a P/F ratio of greater than 120 or receiving high tidal volume ventilation had either no change or an increase in SP-D, WVF, or IL-8 concentrations. CONCLUSION: NBM is associated with decreased biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients receiving low tidal volume ventilation and those with a P/F ratio less than or equal to 120.
Asunto(s)
Bloqueo Neuromuscular/efectos adversos , Síndrome de Dificultad Respiratoria/fisiopatología , Adulto , Anciano , Análisis de Varianza , Biomarcadores/análisis , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Interleucina-8/análisis , Interleucina-8/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Bloqueo Neuromuscular/métodos , Estudios Prospectivos , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/sangre , Síndrome de Dificultad Respiratoria/sangre , Volumen de Ventilación Pulmonar/fisiología , Factor de von Willebrand/análisisRESUMEN
Surfactant protein-D (SP-D) is a collectin, which plays an important role in airway protection and inflammation. The molecule has both pro- and anti-inflammatory capacities depending on its molecular size. Its involvement in joint diseases is largely unknown and the aim of this investigation was to study SP-D occurrence and distribution in the synovial membrane of patients with long-standing rheumatoid arthritis (RA) and osteoarthritis (OA). Six RA patients and six OA patients, who underwent total hip arthroplasty, were included in the study. Synovial tissue biopsies were obtained during surgery and subsequently prepared for immunohistochemistry. In this first, small-scale comparative study on the occurrence of SP-D in the synovial membrane of RA and OA, we report that SP-D was only present in the microvascular endothelium in subsynovial and pannus tissue and that the immunostaining was much stronger than in OA. This distribution pattern suggests that SP-D modulates RA inflammatory activities.
Asunto(s)
Artritis Reumatoide/metabolismo , Osteoartritis/metabolismo , Proteína D Asociada a Surfactante Pulmonar/análisis , Membrana Sinovial/química , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína D Asociada a Surfactante Pulmonar/fisiologíaRESUMEN
Trauma is a major factor that contributes to the risk for acute respiratory distress syndrome (ARDS). Biomarkers that predict the risk, diagnosis, treatment response and prognosis of ARDS after trauma have been widely investigated. In addition to their applications in clinical diagnosis and treatment, these biomarkers provide important insights into our understanding of the pathogenesis of ARDS. This review begins with a brief introduction regarding the incidence and pathogenesis of trauma-associated ARDS. Then, we focus on reviewing the clinical trials that have been designed to investigate the value of biomarkers in ARDS after trauma. Biomarkers with a confirmed value in ARDS have been organized on the basis of key pathogenic processes that are central to ARDS and are described in detail. Among these, angiopoietin 2 (Ang-2), L-selectin, Clara cell protein 16 (CC16), soluable receptor for advanced glycation end products (sRAGE), Surfactant protein D (SP-D), histones, mtDNAs and some biomarker panels had a certain association with the diagnosis and prognosis of trauma-related ARDS. Further investigations are needed regarding the design of trials, the best sampling approaches and the optimal combinations of the biomarker panels.
Asunto(s)
Biomarcadores/análisis , Síndrome de Dificultad Respiratoria/diagnóstico , Heridas y Lesiones/complicaciones , Angiopoyetina 2/análisis , Biomarcadores/sangre , ADN Mitocondrial/análisis , ADN Mitocondrial/sangre , Histonas/análisis , Histonas/sangre , Humanos , Selectina L/análisis , Selectina L/sangre , Pronóstico , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/sangre , Receptor para Productos Finales de Glicación Avanzada/análisis , Receptor para Productos Finales de Glicación Avanzada/sangre , Síndrome de Dificultad Respiratoria/etiología , Uteroglobina/análisis , Uteroglobina/sangreRESUMEN
OBJECTIVE: To observe the levels of pulmonary surfactant proteins A and D (SP-A, SP-D) in bronchoalveolar lavage fluid (BALF) of children with pneumonia, and to explore their relationships with clinical characteristics. METHODS: Thirty-five children with pneumonia were enrolled in this study. Differential cell counts were obtained by Countstar counting board. The levels of SP-A and SP-D in BALF were detected using ELISA. RESULTS: In children with pneumonia, SP-D levels were significantly higher than SP-A levels (P<0.001). SP-D levels were negatively correlated with the neutrophil percentage in BALF (r(s)=-0.5255, P<0.01). SP-D levels in BALF in children with increased blood C-reactive protein levels (>8â mg/L) were significantly lower than in those with a normal level of C-reactive protein (P<0.05). Compared with those in children without wheezing, SP-D levels in children with wheezing were significantly lower (P<0.01). There was no correlation between SP-A levels and clinical characteristics. CONCLUSIONS: SP-D levels in BALF are significantly higher than SP-A levels, and have a certain correlation with clinical characteristics in children with pneumonia. As a protective factor, SP-D plays a more important role than SP-A in regulating the immune and inflammatory responses.
Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Neumonía/metabolismo , Proteína A Asociada a Surfactante Pulmonar/análisis , Proteína D Asociada a Surfactante Pulmonar/análisis , Proteína C-Reactiva/análisis , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , MasculinoRESUMEN
OBJECTIVE: A controlled human exposure study was conducted to investigate the impact of inhalational exposures to wood smoke PM2.5 on measured concentrations of airway and systemic inflammatory biomarkers. METHODS: Mimicking wildland firefighter activities, 10 participants were exposed to three doses of wood smoke PM2.5 (filtered-air, 250âµg/m, and 500âµg/m) while exercising on a treadmill. Exhaled breath condensate (EBC) and blood plasma samples were obtained pre-, immediately post-, and 1-hour postexposure. 8-isoprostane, pH, and myeloperoxidase were measured in EBC, while H2O2, surfactant protein D, and pentraxin-3 (PTX3) were measured in both EBC and plasma. RESULTS: Only pH, 8-isoprostane, and PTX3 displayed significant changes when comparing pre- and postexposures. CONCLUSIONS: Markers of inflammation and oxidative stress, including PTX3, pH, and 8-isoprostane in EBC and/or plasma, are sensitive to wood smoke inhalation, with further investigations warranted.
Asunto(s)
Bomberos , Inflamación/sangre , Exposición por Inhalación/efectos adversos , Estrés Oxidativo/fisiología , Material Particulado/toxicidad , Humo/efectos adversos , Biomarcadores/sangre , Pruebas Respiratorias , Proteína C-Reactiva/análisis , Dinoprost/análogos & derivados , Dinoprost/análisis , Incendios , Humanos , Peróxido de Hidrógeno/análisis , Concentración de Iones de Hidrógeno , Masculino , Peroxidasa/análisis , Proteína D Asociada a Surfactante Pulmonar/análisis , Componente Amiloide P Sérico/análisis , MaderaRESUMEN
OBJECTIVES: In a previous study on smelter workers we, found significant relationship between exposure to dust and accelerated annual decline in forced expiratory volume in 1â s (FEV1). In this cross-sectional study at the end of a follow-up, we aimed to investigate the possible association between annual decline in FEV1 and markers of airways, and systemic inflammation in smelter workers. METHODS: Employees (n=76 (27 current smokers)) who had been part of a longitudinal study (9-13â years) that included spirometry (>6 measurements) and respiratory questionnaires, performed induced sputum, exhaled NO and had blood drawn. Participants with annual decline in FEV1≥45â mL were compared with participants with annual decline <45â mL; also 26 non-exposed controls were included. RESULTS: Compared with non-exposed controls, smelter workers demonstrated a significantly increased percentage of neutrophils (mean (SD)) (57% (17) vs 31% (15)) and matrix metalloproteinases 8 (MMP-8) levels in sputum, and MMP-9, surfactant protein D (SpD) and transforming growth factor ß (TGFb) levels in blood. A significant association in FEV1≥45â mL was found for blood neutrophils when controlling for smoking habits (OR=1.7 (95% CI 1.0 to 2.8), p=0.045). Airway and blood protein markers were not associated with annual decline in FEV1. CONCLUSIONS: All workers displayed airway and systemic inflammation characterised by increased levels of neutrophils and MMP-8 in sputum, and MMP-9, SpD and TGFß in blood compared with non-exposed controls. Blood neutrophils in particular were significantly elevated in those workers with the most rapid decline in lung function. A similar observation was not seen with airway neutrophils. In the present study, we were able to identify systemic but not airway inflammatory markers that can predict increased decline in FEV1 in smelter workers.
Asunto(s)
Volumen Espiratorio Forzado , Metales/efectos adversos , Neutrófilos/efectos de los fármacos , Exposición Profesional/efectos adversos , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Industrias , Modelos Lineales , Masculino , Metaloproteinasas de la Matriz Secretadas/análisis , Persona de Mediana Edad , Óxido Nítrico/análisis , Noruega/epidemiología , Proteína D Asociada a Surfactante Pulmonar/análisis , Fumar/epidemiología , Espirometría , Esputo/química , Esputo/inmunología , Encuestas y Cuestionarios , Factor de Crecimiento Transformador beta/análisisRESUMEN
Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar proteinosis (PAP), a process in which accumulated surfactants are washed out of the lung with 0.5-2.0 l of saline aliquots for 10-30 wash cycles. The method has been established empirically. In contrast, the kinetics of protein transfer into the lavage fluid has not been fully evaluated either theoretically or practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We made accurate timetables for each stage of WLL, namely, instilling, retaining, draining, and preparing. Subsequently, we measured the volumes of both instilled saline and drained lavage fluid, as well as the concentrations of proteins in the drained lavage fluid. We also proposed a mathematical model of protein transfer into the lavage fluid in which time is a single variable as the protein moves in response to the simple diffusion. The measured concentrations of IgG, transferrin, albumin, and ß2-microglobulin closely matched the corresponding theoretical values calculated through differential equations. Coefficients for transfer of ß2-microglobulin from the blood to the lavage fluid were two orders of magnitude higher than those of IgG, transferrin, and albumin. Simulations using the mathematical model showed that the cumulative amount of eliminated protein was not affected by the duration of each cycle but dependent mostly on the total time of lavage and partially on the volume instilled. Although physicians have paid little attention to the transfer of substances from the lung to lavage fluid, WLL seems to be a procedure that follows a diffusion-based mathematical model.