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The prevalence of chronic obstructive pulmonary disease (COPD) has increased more rapidly in women than in men during the past two decades. Clinical presentation, comorbidities and prognosis may differ between genders and may influence management decisions. The influence of gender on COPD expression has not been clearly explained to date. Thus, the aim of this study was to evaluate significant differences between women and men suffering from COPD, regarding clinical presentation, pulmonary function test results, comorbidities, and prognosis. We prospectively recruited 470 patients with stable COPD with a history of smoking (152 women, 318 men, mean age 65.5 ± 8.8 vs. 66.6 ± 9.4 years, respectively). Comorbidities and exacerbations were recorded. Spirometry, body plethysmography, carbon monoxide diffusing capacity and 6-min walk tests were performed. The BODE prognostic score was also calculated. We found that women smoked less in comparison to men (30.4 vs. 41.9 pack-years, p < 0.05), showed more exacerbations (2.5 vs. 1.7, p = 0.01), higher forced expiratory volume in 1 s (FEV1%predicted), and increased residual volume/total lung capacity (RV/%TLC), but they had the same intensity of dyspnea. Women showed fewer comorbidities, on average, per patient (5.4 vs. 6.4, p = 0.002), but had a higher prevalence of at least seven comorbidities per patient (48.7% of women vs. 33.0% of men, p < 0.05). Women also had a significantly worse prognosis (4.6 vs. 3.1 BODE score, p < 0.05) that correlated with the number of comorbidities (r = 0.33, p < 0.01). In conclusion, this study strongly supports the existence of different gender phenotypes in COPD, especially regarding exacerbations, comorbidities, and prognosis. The gender difference may indicate a need for a targeted assessment and management of COPD in women and men.
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Comorbilidad , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Factores Sexuales , Anciano , Femenino , Volumen Espiratorio Forzado , Humanos , Pulmón , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Fumar , EspirometríaRESUMEN
Chronic exposure to detrimental environmental factors may induce immunogenic cell death of structural airway cells in chronic obstructive pulmonary disease (COPD). Damage-associated molecular patterns (DAMPs) is a family of heterogeneous molecules released from injured or dead cells, which activate innate and adaptive immune responses on binding to the pattern recognition receptors on cells. This study seeks to define the content of DAMPs in the bronchoalveolar lavage fluid (BALF) and serum of COPD patients, and the possible association of these molecules with clinical disease features. Thirty COPD in advanced disease stages were enrolled into the study. Pulmonary function tests, arterial blood gas content, 6-minute walk test, and BODE index were assessed. The content of DAMPs was estimated using the commercial sandwich-ELISA kits. We found differential alterations in the content of various DAMP molecules. In the main, BALF DAMPs positively associated with age, forced expiratory volume in one second (FEV1), and residual volume (RV); and inversely with PaO2, residual volume/total lung capacity (RV/TLC) ratio, and the disease severity staging. In serum, DAMPS positively associated with the intensity of smoking and inversely with age, PaO2, and TLC. In conclusion, DAMPs are present in both BALF and serum of COPD patients, which points to enhanced both local in the lung environment as well as systemic pro-inflammatory vein in this disease. These molecules appear involved with the lung damage and clinical variables featuring COPD. However, since the involvement of various DAMPs in COPD is variable, the exact role they play is by far unsettled and is open to further exploration.
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Alarminas/análisis , Líquido del Lavado Bronquioalveolar/química , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Volumen Espiratorio Forzado , Humanos , Pulmón/fisiopatología , Pruebas de Función Respiratoria , Suero/químicaRESUMEN
Obstructive sleep apnea (OSA) is a condition of breathing pathology occurring during sleep, characterized by repeated episodes of upper airway obstruction. The aim of the study was to determine the occurrence of airway obstruction in smoking males with OSA in whom lung function tests had not been performed before. One hundred and four current smokers selected from 1241 patients were enrolled for the research. The subjects included in the study smoked minimum 20 cigarettes a day for at least 10 years. The diagnosis of OSA was confirmed by polysomnography (PSG) in the Sleep Laboratory and subjects were assigned to one of three groups, depending on the severity of OSA. The control group consisted of 30 age-matched male smokers in whom OSA was not confirmed in PSG. Patients from the study and control group scored ≥ 11points in the Epworth Sleepiness Scale. Spirometry, impulse oscillometry, and body plethysmography were used to assess pulmonary function. Airflow limitation in subjects of the control group and OSA patients was confirmed. There were no significant differences in the incidence of bronchial obstruction between the control and study groups, and among the patients of various OSA severity. We conclude that the severity of OSA in smokers does not associate with the presence of airway obstruction. However, the increased peripheral respiratory resistance found in oscillometry did relate to a longer smoking time in OSA patients.
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Obstrucción de las Vías Aéreas/diagnóstico , Apnea Obstructiva del Sueño/diagnóstico , Fumadores , Estudios de Casos y Controles , Humanos , Masculino , Pletismografía , Polisomnografía , EspirometríaRESUMEN
Macrophages in malignant pleural effusions (MPEs) demonstrate a promalignant phenotype. They release mediators, which are a source of inflammation within the pleura. We established in vitro model proving that pleural macrophages isolated from effusions affect cancer cells in their pro- or anti-apoptotic activity via humoral mediators. Additionally, we measured concentrations of selected transcription factors in cancer cells. Pleural macrophages can affect the apoptosis of cancer cells via intercellular mediators which trigger different signal transductors in cancer cells. The observed effect is connected to the composition of exudate which may vary depending on its origin, either malignant or nonmalignant.
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Apoptosis , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Macrófagos/patología , Neoplasias/patología , Derrame Pleural/patología , Transducción de Señal , Factores de Transcripción/metabolismo , Humanos , Espacio Intracelular/metabolismo , Macrófagos/metabolismo , Neoplasias/metabolismo , Derrame Pleural/metabolismo , Células Tumorales CultivadasRESUMEN
PURPOSE: As life expectancy in cystic fibrosis (CF) increases, questions regarding its potential impact on cardiovascular health arise. Soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin (sP-selectin) are proposed as biomarkers of cardiovascular disease. We aimed to: compare their concentrations in clinically stable CF patients and healthy subjects (HS) and verify whether they independently correlate with CF characteristics. METHODS: Serum sVCAM-1 and sP-selectin levels were measured using ELISA. CF was characterized using: forced expiratory volume in 1 s, exocrine pancreatic and CF-related liver disease status, Pseudomonas aeruginosa colonization, serum high-sensitivity C-reactive protein, and body mass index (BMI). CFTR genotypes were classified as severe (classes I and II) or other. RESULTS: 108 CF patients and 51 healthy subjects volunteered for the study. In the CF group BMI was lower (median [IQR]: 20.5 kg/m2 [18.4-22.2] vs. 21.6 kg/m2 [19.9-23.4], p = 0.02) and hsCRP levels were higher (3.6 mg/L [1.1-7.1] vs. 0.5 mg/dL [0.3-1.0], p < 10-10). While sVCAM-1 concentrations were greater in CF patients (1018 ng/mL [851-1279] vs. 861 ng/mL [806-979], p < 10-4), sP-selectin levels did not differ (155 ng/mL [129-188] vs. 156 ng/mL [144-177], p = 0.48). None of the multivariable regression models was valid for the prediction of sVCAM-1 and sP-selectin in CF. CONCLUSIONS: We found higher sVCAM-1 concentrations in CF patients than in healthy subjects, which were not explained by CF characteristics. Further research is required to check whether sVCAM-1 is a marker of microangiopathy in CF.
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Fibrosis Quística/sangre , Selectina-P/sangre , Molécula 1 de Adhesión Celular Vascular/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Transversales , Fibrosis Quística/diagnóstico , Fibrosis Quística/microbiología , Fibrosis Quística/fisiopatología , Ensayo de Inmunoadsorción Enzimática , Insuficiencia Pancreática Exocrina/sangre , Insuficiencia Pancreática Exocrina/diagnóstico , Femenino , Volumen Espiratorio Forzado , Humanos , Modelos Lineales , Pulmón/microbiología , Pulmón/fisiopatología , Masculino , Análisis Multivariante , Polonia , Valor Predictivo de las Pruebas , Pronóstico , Infecciones por Pseudomonas/sangre , Infecciones por Pseudomonas/diagnóstico , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Regulación hacia Arriba , Adulto JovenRESUMEN
The aim of this study was to elucidate body composition, anthropometric indices, and hydration status in obstructive sleep apnea (OSA) patients, taking into account different disease stages, gender, and the possibility of the presence of cachexia. There were 98 OSA patients and 23 control subjects enrolled into the study. All study participants underwent polysomnography examination. Body mass index (BMI), fat mass index (FMI), fat free mass, muscle mass, body cell mass, total body water, and extracellular and intracellular water were evaluated. The neck, abdominal, and waist circumference was measured. We found that overweight and obesity were present in 96% of patients. Cachexia was present in one OSA individual with comorbidities. Apnea-hypopnea index correlated with the neck and waist circumference, and with BMI in OSA patients. All muscle indices and water contents above outlined were significantly higher in severe OSA compared with control subjects. BMI, FMI, neck circumference, and extracellular water were greater in a subset of severe OSA compared with a moderate OSA stage. The female OSA patients had a higher FMI than that present in males at a comparable BMI. We conclude that the most body composition indices differed significantly between severe OSA patients and control subjects. A higher FMI in females at a comparable BMI could be due to a discordance between BMI and FMI. Cachexia occurs rarely in OSA and seems to coexist with comorbidities.
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Composición Corporal , Caquexia/complicaciones , Obesidad/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Índice de Masa Corporal , Femenino , Humanos , Masculino , Polisomnografía , Factores de RiesgoRESUMEN
Granulomatosis with polyangiitis (GPA) is a rare disease of unknown aetiology, characterized by necrotizing inflammation of small and medium-sized vessels and formation of granulomas. The disease typically involves the upper and lower respiratory tracts and the kidneys, but it can occur in many other locations, often giving a surprising clinical picture. The majority of patients have autoantibodies against cytoplasm of neutrophils (ANCA), of which a pathogenetic role is postulated. The disease affects mostly middle-aged and elderly people, with a predominance of Caucasians. Before the era of immunosuppressive therapy GPA was associated with high early mortality. Nowadays, we have a treatment that gives remission in the majority of patients. The decision about the method of treatment should be made depending on the clinical form of the disease (local or generalized, refractory). Standard remission induction therapy in the generalized disease is cyclophosphamide in combination with steroids. This therapy, however effective, is associated with a number of side effects. In addition, some patients are resistant to standard therapy, and half of them experience relapses. Therefore, there is need for further research for alternative treatment and maintenance therapy. Currently, hopes are raised by biological agents. Among them, the best studied so far is rituximab, which found a place in the current recommendations of EULAR as an alternative drug for patients with refractory disease. The article discusses the clinical picture of GPA, diagnosis and currently recommended treatment.
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Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Recurrencia , Inducción de Remisión , RituximabRESUMEN
In recent years, questionnaires were published in English to assess the quality of life of patients with PCD (Primary Ciliary Diskinesia) for adults, adolescents aged 13-17 years, and children aged 6-12 years and their caregivers. This study aimed to prepare Polish versions of the questionnaires and validate them in specific age groups with the participation of Polish patients with PCD. The individual questionnaires were translated and discussed with the involvement of the creator of the original questionnaire in English. Patients completed the questionnaires according to their affiliation with one of the groups. Validation was based on internal consistency analysis (Cronbach's alpha coefficient and split-half reliability) and test-retest reliability (intraclass correlation coefficient-ICC). The internal consistency of all questionnaires was from moderate to very good (Cronbach's alpha 0.67-0.91, split-half reliability 0.53-0.95). The consistency of the measurements showed excellent repeatability (ICC 0.67-0.91). The surveyed Polish PCD patients rated their quality of life quite well (63-77%). QOL questionnaires for patients with PCD can be used routinely during each medical check-up as a simple tool to provide the doctor with an indication of the effectiveness of treatment and the impact of the disease on the patient's quality of life.
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Calidad de Vida , Humanos , Calidad de Vida/psicología , Encuestas y Cuestionarios/normas , Polonia , Adolescente , Niño , Masculino , Femenino , Reproducibilidad de los Resultados , Adulto , Trastornos de la Motilidad CiliarRESUMEN
Avian predation is one of the most probable factors maintaining polymorphism of shell coloration in Cepaea nemoralis. This assumption is justified by the fact that birds frequently forage on snails and their prey choice varies with morph coloration. However, in all preceding studies, the conspicuousness of morphs was determined only by using human vision which is significantly different from birds' visual perception. In this study, we assessed how birds perceive colors of four Cepaea nemoralis morphs using physiological models of avian color vision. We calculated combined chromatic and achromatic contrast between shells and three habitat background types as a measure of shell conspicuousness. The degree of background color matching in Cepaea nemoralis depended on both shell morph and habitat type. On average, banded morphs were more conspicuous than unbanded morphs. Morphs were the most cryptic against dry vegetation and the most conspicuous on bare ground. We also found a significant interaction between habitat type and color morph. The relative conspicuousness of shell morphs depended on habitat and was the most variable against green vegetation. Our study provides the first insight into how potential avian predators view Cepaea nemoralis morphs. The results are discussed in light of multiple hypotheses explaining selective predation on Cepaea nemoralis morphs.
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Aves/fisiología , Cadena Alimentaria , Pigmentación/fisiología , Caracoles/fisiología , Percepción Visual/fisiología , Animales , EcosistemaRESUMEN
Nintedanib is a disease-modifying agent licensed for the treatment of IPF. Data on Polish experience with nintedanib in IPF are lacking. The present study aimed to describe the safety and efficacy profiles of nintedanib in a large real-world cohort of Polish patients with IPF. This was a multicenter, retrospective, observational study of IPF patients treated with nintedanib between March 2018 and October 2021. Data collection included baseline clinical characteristics, results of pulmonary function tests (PFTs), and a six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), and treatment persistence were also retrieved. A total of 501 patients (70% male) with a median age of 70.9 years (IQR 65-75.7) were included in this study. Patients were followed on treatment for a median of 15 months (7-25.5). The majority of patients (66.7%) were treated with the full recommended dose of nintedanib and 33.3% of patients were treated with a reduced dose of a drug. Intermittent dose reductions or drug interruptions were needed in 20% of patients. Over up to 3 years of follow-up, pulmonary function remained largely stable with the minority experiencing disease progression. The most frequent ADRs included diarrhea (45.3%), decreased appetite (29.9%), abdominal discomfort (29.5%), weight loss (32.1%), nausea (20.8%), fatigue (19.2%), increased liver aminotransferases (15.4%), and vomiting (8.2%). A total of 203 patients (40.5%) discontinued nintedanib treatment due to diverse reasons including ADRs (10.2%), death (11.6%), disease progression (4.6%), patient's request (6.6%), and neoplastic disease (2.2%). This real-world study of a large cohort of Polish patients with IPF demonstrates that nintedanib therapy is safe, and is associated with acceptable tolerance and disease stabilization. These data support the findings of previously conducted clinical trials and observational studies on the safety and efficacy profiles of nintedanib in IPF.
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BACKGROUND: Cystic fibrosis (CF) and CF-related liver disease can lead to disturbances in bile acid metabolism. AIM: This study determined serum bile acid concentrations in CF to define their usefulness in liver disease assessment. METHODS: Primary, secondary and conjugated bile acid levels were measured in three CF groups (25 patients each) exhibiting: liver cirrhosis, other liver disease, no liver disease, and in 25 healthy subjects (HS). RESULTS: Bile acid levels were higher in CF patients than in HS, except for glycodeoxycholic acid (GDCA). However, bile acid concentrations did not differ between patients with cirrhosis and other liver involvement. GDCA and deoxycholic acid (DCA) differentiated CF patients with non-cirrhotic liver disease from those without liver disease (GDCA-AUC: 0.924, 95%CI 0.822-1.000, p<0.001; DCA-AUC: 0.867, 95%CI: 0.731-1.000, p<0.001). Principal component analysis revealed that in CF liver disease was related to GDCA, GGTP activity, severe genotype and pancreatic insufficiency. CONCLUSIONS: A CF-specific bile acid profile was defined and shown to relate to liver disease. GDCA differentiates patients with non-cirrhotic liver involvement from those with no detectable liver disease. Hence, GDCA is a candidate for validation as a biomarker of non-cirrhotic progression of liver disease in CF.
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Ácidos y Sales Biliares/sangre , Fibrosis Quística/sangre , Ácido Glicodesoxicólico/sangre , Cirrosis Hepática/diagnóstico , Hepatopatías/diagnóstico , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Fibrosis Quística/complicaciones , Femenino , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Hepatopatías/sangre , Hepatopatías/etiología , Masculino , Adulto JovenRESUMEN
ABSTRACT: The role of regulatory T cells (Tregs), damage-associated molecular patterns (DAMPs), and myeloid-derived suppressor cells (MDSCs) in the mechanism of innate and adaptive immune responses in chronic obstructive pulmonary disease (COPD) is not well understood.Evaluating the presence of Tregs in the bronchoalveolar lavage fluid (BALF) and peripheral blood in patients with COPD, and assessment of the relationship between Tregs, MDSCs, and DAMPs as factors activating innate and adaptive immune responses. Description of the association between immune and clinical parameters in COPD.Thirty-one patients with COPD were enrolled. Clinical parameters (forced expiratory volume in one second [FEV1], forced vital capacity, total lung capacity [TLC], diffusion capacity of carbon monoxide, and B-BMI, O-obstruction, D-dyspnea, E-exercise [BODE]) were assessed. Tregs and MDSCs were investigated in the BALF and blood using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. The levels of defensin (DEF2), galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-9 (Gal-9), heat shock protein-27 (HSP27), and surfactant protein A were assessed via sandwich enzyme-linked immunosorbent assay.The percentage of Tregs was significantly higher in the blood than in the BALF, in contrast to the mean fluorescence intensity of forkhead box P3 (FoxP3). Significant associations were observed between Tregs and HSP27 (râ=â0.39), Gal-1 (râ=â0.55), Gal-9 (râ=â-0.46), and MDSCs (râ=â-0.50), and between FoxP3 and Gal-1 (râ=â-0.42), Gal-3 (râ=â-0.39), and MDSCs (râ=â-0.43). Tregs and clinical parameters, including FEV1%pred (râ=â0.39), residual volume (RV)%pred (râ=â-0.56), TLC%pred (râ=â-0.55), RV/TLC (râ=â-0.50), arterial oxygen saturation (râ=â-0.38), and arterial oxygen pressure (râ=â-0.39) were significantly correlated. FoxP3 was significantly interlinked with RV/TLC (râ=â-0.52), arterial oxygen pressure (râ=â0.42), and BODE index (râ=â-0.57).The interaction between innate and adaptive immune responses in patients with COPD was confirmed. The expression of Tregs in BALF may have prognostic value in patients with COPD. The conversion of immune responses to clinical parameters appears to be associated with disease severity.
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Células Supresoras de Origen Mieloide , Enfermedad Pulmonar Obstructiva Crónica , Líquido del Lavado Bronquioalveolar , Volumen Espiratorio Forzado/fisiología , Factores de Transcripción Forkhead/metabolismo , Proteínas de Choque Térmico HSP27 , Humanos , Pulmón , Células Supresoras de Origen Mieloide/metabolismo , Oxígeno/metabolismo , Linfocitos T Reguladores/metabolismoRESUMEN
Macrophages are among the infiltrate components of most malignant tumors. Tumor-associated macrophages (TAMs) may secrete a variety of humoral factors, which promote or inhibit tumor growth. In general, depending on their activation pathway, macrophages exhibit two different patterns of phenotype, M1 or M2. It is assumed that TAMs comprise pattern M2. In the malignant pleural effusion, macrophages are a frequent component of cytological evaluation. In this microenvironment, TAMs could be involved in the development of immunity. The phenotype of macrophages represented in malignant and non-malignant pleural effusions is unknown. In this study, macrophages were isolated from 38 pleural effusions (15 malignant and 23 non-malignant) and the expression of a variety of immune mediators and their receptors was assessed to determine the type of activation (M1 vs. M2). The expression of mRNA was analyzed for IL-1ß, IL-4, IL-6, IL-10, IL-11, IL-18, TNFα, TGFß1, IL1R1, IL1RAP, TLR2, TLR4, VLA4, CD62L, MMP2, MMP9, VEGFA, PDGFA, and PDGFB. In immunohistochemical evaluation, the expressions of CD68, mesothelin, MAC387, IL-1ß, IL-6, IL-10, IL-12, TNFα, and CD105 were assessed. The cytoplasmic expression of IFNγ, TNFα, IL-6, and IL-10 and the surface expression of CD11a, CD14, CD15, CD16, CD23, CD25, CD45, CD54, CD62L, CD69, VLA2, VLA3, VLA4, VLA6, TLR2, TLR4, and CCR7 were tested using flow cytometry. In supernatants from macrophages cultures, TNFα, IL-1ß, IL-6, IL-8, IL-10, IL-12, MCP1, and VEGF were investigated by cytometric beads array method (CBA flex sets) and TGFß1 by ELISA. Our results indicate that macrophages from malignant and non-malignant pleural effusions differ from each other and suggest that macrophages isolated from non-malignant effusions show a pattern comparable to M1 while those isolated from malignant effusions express similarity to M2 phenotype, but they have not shown a classical M2 pattern.
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Perfilación de la Expresión Génica , Macrófagos/metabolismo , Derrame Pleural Maligno/genética , Derrame Pleural/genética , Antígenos CD/genética , Antígenos CD/inmunología , Antígenos CD/metabolismo , Citocinas/genética , Citocinas/inmunología , Citocinas/metabolismo , Citometría de Flujo , Humanos , Inmunohistoquímica , Inmunofenotipificación , Macrófagos/clasificación , Macrófagos/inmunología , Derrame Pleural/inmunología , Derrame Pleural/metabolismo , Derrame Pleural Maligno/inmunología , Derrame Pleural Maligno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of ß-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).
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Ciclodextrinas/química , Fibrosis Quística/dietoterapia , Liposomas/química , Triglicéridos/química , Vitaminas/administración & dosificación , Adolescente , Adulto , Calcifediol/sangre , Colecalciferol/administración & dosificación , Colecalciferol/sangre , Suplementos Dietéticos , Insuficiencia Pancreática Exocrina/dietoterapia , Femenino , Humanos , Masculino , Resultado del Tratamiento , Vitamina A/administración & dosificación , Vitamina A/sangre , Vitamina D/administración & dosificación , Vitamina D/sangre , Vitamina E/administración & dosificación , Vitamina E/sangre , Vitamina K 2/administración & dosificación , Vitamina K 2/análogos & derivados , Vitaminas/sangre , Vitaminas/química , Adulto Joven , beta Caroteno/administración & dosificaciónRESUMEN
Myeloid-derived suppressor cells (MDSCs) are present in the human lung microenvironment, and they may be involved in the local inflammatory process in chronic obstructive pulmonary disease (COPD). Chronic inflammation in COPD may induce immunogenic cell death of structural airway cells, causing the release of damage-associated molecular patterns (DAMPs). DAMPs may activate the innate and adaptive immune system. The relationship between MDSCs and DAMPs in COPD is poorly described in the available literature. Objectives. (1) Assessment of MDSC percentage and DAMP concentration in bronchoalveolar lavage fluid (BALF) and peripheral blood. (2) Analysis of the relationship between MDSC percentage and chosen DAMPs. Patients and Methods. 30 COPD patients were included. Using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry, MDSCs were assessed in BALF and peripheral blood. The concentration of DAMPs was estimated using sandwich ELISA. Using the Bradford method, the total protein concentrations were evaluated. Results. The percentage of MDSCs among MC in BALF correlated well with the concentration of defensin and heat shock protein 27. Assessing the percentage of MDSCs among all leukocytes in BALF, we revealed a significant correlation with the concentration of defensin, hyaluronic acid, and surfactant protein A. No dependencies occurred between DAMPs and MDSCs in peripheral blood. Conclusion. MDSCs and DAMPs occur in the COPD patient lung microenvironment. Significant correlations between them found in BALF may indicate their influence on the local inflammatory process in COPD. These relationships allow better understanding of the inflammatory process in COPD.
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Líquido del Lavado Bronquioalveolar/inmunología , Pulmón/metabolismo , Células Supresoras de Origen Mieloide/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Anciano , Líquido del Lavado Bronquioalveolar/química , Defensinas/metabolismo , Femenino , Proteínas de Choque Térmico/metabolismo , Humanos , Ácido Hialurónico/metabolismo , Inflamación/fisiopatología , Pulmón/patología , Masculino , Persona de Mediana Edad , Chaperonas Moleculares/metabolismo , Células Supresoras de Origen Mieloide/química , Células Supresoras de Origen Mieloide/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Proteína A Asociada a Surfactante Pulmonar/metabolismoRESUMEN
BACKGROUND: The interest in cystic fibrosis (CF) dyslipidaemia as a potential risk factor for cardiovascular disease is increasing with patients' survival. This study aimed to investigate CF dyslipidaemia, its clinical correlates and links to oxidized low-density lipoprotein (oxLDL), adiponectin, and apolipoprotein E (APOE). METHODS: This cross-sectional study assessed clinical characteristics of CF, as well as the serum lipid profile, oxLDL, adiponectin, and APOE. RESULTS: In total, 108 CF subjects were enrolled in this study, with a median age of 22â¯years, BMI of 20.5â¯kg/m2, FEV1% of 61%, of which 81% were pancreatic insufficient (PI). Healthy subjects (HS; nâ¯=â¯51) were in similar age. Hypocholesterolaemia occurred in 31% of CF subjects and in no HS. Hypertriglyceridaemia concerned 21% of patients (HS: 8%, pâ¯=â¯.04), and low HDL-C 45% (HS: 6%, pâ¯<â¯.0001). At least one of these three CF dyslipidaemia disturbances was present in 62% of CF subjects, but there were no significant differences in oxLDL, oxLDL/LDL-C ratio, adiponectin, and APOE between CF and HS groups. PI was independently associated with low total cholesterol, LDL-C, and non-high density lipoprotein cholesterol, with age and sex also modifying lipid levels. In CF (n =â¯42), triglycerides did not correlate with serum tumour necrosis factor α (TNF-α). CONCLUSIONS: CF dyslipidaemia is highly prevalent and heterogenous. The lipid profile weakly associates with the clinical characteristics of CF as well as oxLDL, adiponectin, and APOE. Further research is needed, especially regarding HDL function in CF, the causes of hypertriglyceridaemia, and the value of essential fatty acid supplementation for CF dyslipidaemia.
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Fibrosis Quística/complicaciones , Dislipidemias/etiología , Adiponectina/sangre , Adulto , Apolipoproteínas E/sangre , Correlación de Datos , Estudios Transversales , Fibrosis Quística/sangre , Dislipidemias/sangre , Femenino , Humanos , Lipoproteínas LDL/sangre , Masculino , Adulto JovenRESUMEN
INTRODUCTION: Bronchial artery embolisation (BAE) is one of the methods used in massive and recurring haemoptysis. The aim of the study is to determine the effectiveness and complications of bronchial artery embolisation in recurring haemoptysis. MATERIAL AND METHODS: The analysis included 47 embolisation procedures performed on 30 patients treated between 2011 and 2017 in the Department of Respiratory Medicine, Allergology and Pulmonary Oncology due to haemoptysis. The patient's age ranged between 18 and 71 years, while mean age at the time of BAE was 33.5 years. Patients with tuberculosis constituted 73.33% (n = 22) of the sample and underwent 31 embolisation procedures in total. The remaining part of the sample (n = 8) collectively underwent 16 BAEs. The analysis was conducted by verifying the medical documentation, as well as carrying face-to-face and phone conversations. RESULTS: Immediate control due to the inhibition of bleeding was obtained in 95.75% of cases. Recurrence within 3 days of BAE was reported in 5 patients (10.63%), and 4 re-embolisation procedures were conducted. In 10 patients (33.33%), recurrence was observed during the first year post-BAE, while it was reported in 17 cases during the whole observation period (56.66% of patients). The subjects who underwent re-embolisation demonstrated recurrence-free periods lasting from 2 days to 63 months. In patients with recurrence but no re-embolisation, the shortest and longest haemoptysis-free time was 2 and 35 months, respectively. 11 patients (36.66%) required several embolisation procedures during the whole observation period. CONCLUSIONS: BAE is a highly successful procedure in treating haemoptysis. The risk of complications is low.
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Arterias Bronquiales/fisiopatología , Embolización Terapéutica/métodos , Hemoptisis/terapia , Adulto , Anciano , Femenino , Hemoptisis/etiología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
Damage-associated molecular pattern (DAMP) molecules can initiate an immune response through Toll-like receptors (TLRs). DAMPs are released from cells as a response to the extracellular danger and can be by-products of tissue damage. In cancer microenvironment necrotic cells release debris which has potency to become DAMPs. Non-small cell lung cancer (NSCLC) is often accompanied by pleural effusion (PE), which contains a variety of DAMPs. Surfactant protein A (SP-A) and heat shock protein 70 (Hsp70) are important DAMPs in the respiratory tract. The aim of this study was to determine a correlation between SP-A or Hsp70 and development of PE in the course of NSCLC. Moreover, we aimed to determine relationships between DAMPs and certain humoral factors associated with formation and persistence of PE as well as pleural-residing macrophages. In 34 PE samples, we estimated concentration of SP-A, Hsp70, IL-6, IL-18, G-CSF, M-CSF, SCF, SDF1α, VEGF as well as the fraction of macrophages and their pattern of polarization. We have found correlations between the concentration of the SP-A and Hsp70 and the percentage of PE-derived macrophages, also between concentrations of SP-A and Hsp70, and cytokines which participate in inflammation and processes involved in remodeling of extracellular matrix (ECM). Our data indicate an important role of SP-A during the development of PE associated with NSCLC. We suggest that measurement of concentration level of SP-A can be helpful in the course of diagnosis of malignant PE associated with NSCLC.
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Biomarcadores/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Proteínas HSP70 de Choque Térmico/metabolismo , Neoplasias Pulmonares/inmunología , Macrófagos/fisiología , Derrame Pleural/inmunología , Proteína A Asociada a Surfactante Pulmonar/metabolismo , Diferenciación Celular , Células Cultivadas , Citocinas/metabolismo , Femenino , Humanos , Masculino , Balance Th1 - Th2 , Receptores Toll-Like/metabolismo , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND AND AIMS: Although indirect methods of assessment of the exocrine pancreatic function have become the standard of care in the monitoring of pancreatic status, it still remains a current clinical challenge. Our aim was to compare the width of the pancreatic duct in pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) patients using secretin-enhanced magnetic resonance cholangiopancreatography (SE-MRCP). METHODS: Thirty-seven CF patients were enrolled for this cross-sectional study, including 21 PI and 16 PS, all of whom underwent SE-MRCP. Measurement of the diameter of the pancreatic duct was performed in the head, body, and the tail of the pancreas at the baseline and after 1, 2, 3, 5, and 10 minutes after secretin administration. RESULTS: The diameter of the pancreatic duct in the head of the pancreas after 5 and 10 minutes of secretin injection was greater in PI than in PS patients (median = 2.0 mm [interquartile range: 1.6-3.0] vs. 2.0 mm [1.0-2.0] and 2.0 mm [1.4-2.0] vs 1.0 mm [1.0-2.0], p=0.047 and p=0.040, respectively). Areas under ROC curves for discriminating between PI and PS patients were 0.693 (95% CI 0.521-0.866) and 0.698 (95% CI 0.528-0.868), respectively. No other differences in the width of the duct were identified at the baseline or during SE-MRCP. CONCLUSIONS: The measurement of the diameter of the pancreatic duct during secretin stimulation does not allow for differentiating between PS and PI status in CF patients.
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Pancreatocolangiografía por Resonancia Magnética/métodos , Fibrosis Quística/diagnóstico por imagen , Insuficiencia Pancreática Exocrina/diagnóstico por imagen , Conductos Pancreáticos/diagnóstico por imagen , Secretina/administración & dosificación , Adolescente , Adulto , Estudios Transversales , Diagnóstico Diferencial , Femenino , Humanos , Infusiones Intravenosas , Masculino , Valor Predictivo de las Pruebas , Adulto JovenRESUMEN
INTRODUCTION Myeloidderived suppressor cells (MDSCs) have the potent ability to suppress Tcell function, and are important in the regulation of chronic inflammation and carcinogenesis. MDSCs may influence local and systemic inflammation and carcinogenesis in COPD; however, their presence in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) or their relationship with clinical parameters in COPD has not been studied yet. OBJECTIVES The aim of the study was to assess MDSCs in BALF and PB and to analyze the relationship between MDSCs and clinical parameters in COPD. PATIENTS AND METHODS The study included 64 patients with stable COPD. The clinical parameters of the patients were studied, and MDSCs were assessed using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. RESULTS The percentage of MDSCs in BALF was lower than that in PB (0.63 ±0.90 vs 3.94 ±0.38). In BALF, MDSCs (% of mononuclear cells) correlated with forced expiratory volume in 1 second (rs = -0.30, P = 0.0185), residual volume/total lung capacity (rs = 0.32, P = 0.0148), PaO2 (rs = -0.45, P = 0.0002), arterial oxygen saturation (SaO2; rs = -0.41, P = 0.0008), and diffusion capacity of carbon dioxide (rs = -0.32, P = 0.0211). There was a significant negative correlation between MDSCs (% of all leukocytes) and arterial oxygen pressure (rs = -0.42, P = 0.0006) and SaO2 (rs = -0.37, P = 0.0027). No correlations were found in PB. CONCLUSIONS MDSCs are present in human lung microenvironment and may be involved in local inflammation in COPD. Future studies should focus on a detailed assessment of MDSCs in local and systemic inflammation in COPD.