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BACKGROUND: Asthma is heterogeneous disease with different phenotypes, endotypes and severities. Definition of these subgroups requires the identification of biomarkers in biological samples, and serum proteomics is a useful and minimally invasive method for this purpose. Therefore, the aim of this study was to detect serum proteins whose abundance is distinctively associated with different asthma phenotypes (allergic vs nonallergic) or severities. METHODS: For each group of donors (32 healthy controls, 43 allergic rhinitis patients and 192 asthmatics with different phenotypes and severities), we generated two pools of sera that were analysed by a shotgun MS approach based on combinatorial peptide ligand libraries and iTRAQ-LC-MS/MS. RESULTS: MS analyses identified 18 proteins with a differential abundance. Functional/network study of these proteins identified key processes for asthma pathogenesis, such as complement activation, extracellular matrix organization, platelet activation and degranulation, or post-translational protein phosphorylation. Furthermore, our results highlighted an enrichment of the "Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)" route in allergic asthma and the lectin pathway of complement activation in nonallergic asthma. Thus, several proteins (eg IGFALS, HSPG2, FCN2 or MASP1) displayed a differential abundance between the different groups of donors. Particularly, our results revealed IGFALS as a useful biomarker for moderate-severe allergic asthma. CONCLUSION: Our data suggest a set of serum biomarkers, especially IGFALS, capable of differentiating allergic from nonallergic asthma. These proteins reveal different pathophysiological mechanisms and may be useful in the future for diagnosis, prognosis or targeted therapy purposes.
Assuntos
Asma , Proteômica , Asma/diagnóstico , Biomarcadores , Cromatografia Líquida , Humanos , Espectrometria de Massas em TandemRESUMO
Discriminating between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains difficult. Thus, novel and efficient biomarkers are required for the diagnosis of pleural effusion (PE). The aim of this study was to validate calprotectin as a diagnostic biomarker of PE in clinical settings. A total of 425 patients were recruited, and the pleural fluid samples collected had BPE in 223 cases (53.7%) or MPE in 137 patients (33%). The samples were all analysed following the same previously validated clinical laboratory protocols and methodology. Calprotectin levels ranged from 772.48 to 3,163.8 ng/mL (median: 1,939 ng/mL) in MPE, and 3,216-24,000 ng/mL in BPE (median: 9,209 ng/mL; p < 0.01), with an area under the curve of 0.848 [95% CI: 0.810-0.886]. For a cut-off value of ≤ 6,233.2 ng/mL, we found 96% sensitivity and 60% specificity, with a negative and positive predictive value, and negative and positive likelihood ratios of 96%, 57%, 0.06, and 2.4, respectively. Multivariate analysis showed that low calprotectin levels was a better discriminator of PE than any other variable [OR 28.76 (p < 0.0001)]. Our results confirm that calprotectin is a new and useful diagnostic biomarker in patients with PE of uncertain aetiology which has potential applications in clinical practice because it may be a good complement to cytological methods.
Assuntos
Complexo Antígeno L1 Leucocitário/análise , Derrame Pleural Maligno/diagnóstico , Derrame Pleural/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , Pleura/patologia , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espanha/epidemiologiaRESUMO
The relationship between obesity and asthma exacerbations is still under debate. The aim of our work is to analyse the relationship between obesity and hospital re-admissions in asthmatics. A review was retrospectively performed on all hospital admissions of adult patients due to asthma exacerbation occurring in our hospital for 11 years. All those cases with asthma as the first diagnosis in the discharge report were included, or those with asthma as the second diagnosis provided when the first diagnosis was respiratory infection or respiratory failure. Only the first hospital admission of each patient was included in this study. The Odds Ratios of a higher incidence of early/late readmissions due to asthma exacerbation were calculated using a binary logistic regression, using the body mass index (BMI) as independent variable, adjusted for all the variables included in the study. The study included 809 patients with a mean age of 55.6 years, and 65.2% were female. The majority (71.4%) were obese or overweight. No significant relationship was observed in the univariate or multivariate analyses between overweight or obesity and the early or late hospital readmissions due to asthma. Therefore, obesity does not seem to be a determining factor in the risk of asthma exacerbations.
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INTRODUCTION: Diagnosis of pleural infection (PI) may be challenging. The purpose of this paper is to develop and validate a clinical prediction model for the diagnosis of PI based on pleural fluid (PF) biomarkers. METHODS: A prospective study was conducted on pleural effusion. Logistic regression was used to estimate the likelihood of having PI. Two models were built using PF biomarkers. The power of discrimination (area under the curve) and calibration of the two models were evaluated. RESULTS: The sample was composed of 706 pleural effusion (248 malignant; 28 tuberculous; 177 infectious; 48 miscellaneous exudates; and 212 transudates). Areas under the curve for Model 1 (leukocytes, percentage of neutrophils, and C-reactive protein) and Model 2 (the same markers plus interleukin-6 [IL-6]) were 0.896 and 0.909, respectively (not significant differences). However, both models showed higher capacity of discrimination than their biomarkers when used separately (P < 0.001 for all). Rates of correct classification for Models 1 and 2 were 88.2% (623/706: 160/177 [90.4%] with infectious pleural effusion [IPE] and 463/529 [87.5%] with non-IPE) and 89.2% (630/706: 153/177 [86.4%] of IPE and 477/529 [90.2%] of non-IPE), respectively. CONCLUSIONS: The two predictive models developed for IPE showed a good diagnostic performance, superior to that of any of the markers when used separately. Although IL-6 contributes a slight greater capacity of discrimination to the model that includes it, its routine determination does not seem justified.
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Introduction The aim of analysing the usefulness of the blood eosinophil count (BEC) as a prognostic marker in exacerbations of patients with Chronic Obstructive Pulmonary Disease (COPD), evaluating its relationship with hospital mortality, the length of stay and the early and late re-admissions. Materials and Methods We have carried out a retrospective study including all patients who required hospital admission from 1 January 2008 to 31 December 2009, with a diagnosis on hospital discharge of COPD exacerbation. These patients were classified using three cut-off points of BEC: less than 200 vs ≥ 200/µL, less than 300 vs ≥ 300/µL and less than 400 vs ≥ 400/µL. Results There were a total of 1626 hospital admissions during the study period with the diagnosis of exacerbation of COPD. In this study we have included 358 patients. The probability of any late re-admission increased with a BEC ≥ 300/µL (odds ratio: 1.684) and for those with a BEC ≥ 400/µL (odds ratio: 2.068). The BEC does not appear to be related to hospital mortality or the probability of early re-admission after an exacerbation of COPD. Conclusions In our study an elevated BEC is associated with a higher incidence of late hospital readmissions in COPD exacerbations.
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CD26 displays variable levels between effector (TH17 â« TH1 > TH2 > Treg) and naïve/memory (memory > naïve) CD4+ T lymphocytes. Besides, IL-6/IL-6R is associated with TH17-differentiation and asthma severity. Allergic/atopic asthma (AA) is dominated by TH2 responses, while TH17 immunity might either modulate the TH2-dependent inflammation in AA or be an important mechanism boosting non-allergic asthma (NAA). Therefore, in this work we have compared the expression of CD26 and CD126 (IL-6Rα) in lymphocytes from different groups of donors: allergic (AA) and non-allergic (NAA) asthma, rhinitis, and healthy subjects. For this purpose, flow cytometry, haematological/biochemical, and in vitro proliferation assays were performed. Our results show a strong CD26-CD126 correlation and an over-representation of CD26- subsets with a highly-differentiated effector phenotype in AA (CD4+CD26-/low T cells) and NAA (CD4-CD26- γδ-T cells). In addition, we found that circulating levels of CD26 (sCD26) were reduced in both AA and NAA, while loss of CD126 expression on different leukocytes correlated with higher disease severity. Finally, selective inhibition of CD26-mRNA translation led to enhanced T cell proliferation in vitro. These findings support that CD26 down-modulation could play a role in facilitating the expansion of highly-differentiated effector T cell subsets in asthma.
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Asma/imunologia , Dipeptidil Peptidase 4/metabolismo , Receptores de Interleucina-6/metabolismo , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia , Adolescente , Adulto , Idoso , Asma/patologia , Estudos de Casos e Controles , Dipeptidil Peptidase 4/sangue , Dipeptidil Peptidase 4/genética , Feminino , Citometria de Fluxo , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-6/genética , Índice de Gravidade de Doença , Adulto JovemRESUMO
INTRODUCTION: The presence of eosinophils in asthma inflammation is a relevant factor in the pathophysiology of the disease, however the relationship between the blood eosinophil count (BEC) with asthma severity and prognosis is still under debate. The aim of this work is to analyze the relationship between the BEC levels and hospital readmissions in patients with asthma. MATERIAL AND METHODS: A review was retrospectively carried out on all admissions of patients over 18â¯years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. The personal characteristics and the asthma personal history of each patient were recorded. The BEC was determined from the first blood sample taken from the patient after their arrival at the hospital. Hospital early, late and frequent readmissions were analyzed using 4 cut-off points; less than 150 eosinophils/µL vs ≥150/µL, less than 200 vs 200 /µL, less than 300 vs ≥300/µL, and less than 400 vs ≥400/µL. RESULTS: We have included 1316 patients, 70% of whom are women, as well as a mean age of 60â¯years, and a mean FEV1 of 73.5% of the reference value. The mean eosinophil blood count was 201.7â¯cells/µL. A BEC ≥300 cells/µL showed a reduction of risk of late readmission of 42%, a BEC ≥400â¯cells/µL showed a reduction in late readmission risk of 41% and decrease in frequent late readmission of 63%. CONCLUSIONS: Our study appears to support that an elevated BEC is associated with a lower incidence of asthma hospital readmissions.
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Asma/sangue , Asma/epidemiologia , Eosinófilos/citologia , Readmissão do Paciente/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Espanha/epidemiologiaRESUMO
The general aim of this study is to create a cohort of asthma patients with varying grades of severity in order to gain greater insight into the mechanisms underlying the genesis and course of this disease. The specific objectives focus on various studies, including imaging, lung function, inflammation, and bronchial hyperresponsiveness, to determine the relevant events that characterize the asthma population, the long-term parameters that can determine changes in the severity of patients, and the treatments that influence disease progression. The study will also seek to identify the causes of exacerbations and how this affects the course of the disease. Patients will be contacted via the outpatient clinics of the 8 participating institutions under the auspices of the Spanish Respiratory Diseases Networking System (CIBER). In the inclusion visit, a standardized clinical history will be obtained, a clinical examination, including blood pressure, body mass index, complete respiratory function tests, and FENO will be performed, and the Asthma Control Test (ACT), Morisky-Green test, Asthma Quality of Life Questionnaire (Mini AQLQ), the Sino-Nasal Outcome Test 22 (SNOT-22), and the Hospital Anxiety and Depression scale (HADS) will be administered. A specific electronic database has been designed for data collection. Exhaled breath condensate, urine and blood samples will also be collected. Non-specific bronchial hyperresponsiveness testing with methacholine will be performed and an induced sputum sample will be collected at the beginning of the study and every 24 months. A skin prick test for airborne allergens and a chest CT will be performed at the beginning of the study and repeated every 5 years.
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INTRODUCTION: In the absence of firm recommendations, we analyzed whether unilateral thoracic puncture is sufficient for bilateral pleural effusion (PE), or if the procedure needs to be performed in both sides. MATERIALS AND METHODS: Prospective study of patients seen consecutively for bilateral PE during a period of 3 years and 9 months. All patients underwent simultaneous bilateral thoracocentesis. The standard protocol variables collected in our hospital served as study parameters. Size of PE, presence of chest pain or fever, or accompanying lung abnormalities, different attenuation values on chest computed tomography, presence of loculated pleural fluid, and radiological resolution in a single side were also evaluated. RESULTS: A total of 36 patients (19 men; mean age 68.5 ± 16.5 years) were included. The etiology of the effusion was different in each side in only 2 patients (5.6%). In 6/32 cases (18.8%), the biological analysis of the pleural fluid (in terms of transudate/exudate) from both sides did not correspond with the etiological diagnosis of the effusion. Correlation between biochemical parameters analyzed in the fluid from both sides (Pearson's correlation coefficient) ranged between 0.74 (LDH) and 0.998 (NT-proBNP). As different diagnoses in each side were found in only 2 patients, the circumstances in which bilateral diagnostic thoracocentesis would be necessary could not be determined. CONCLUSIONS: Simultaneous bilateral thoracocentesis does not appear to be recommendable. Larger series are needed to establish which factors might suggest the need for simultaneous puncture of both PE.
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Derrame Pleural/cirurgia , Toracentese/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/patologia , Estudos ProspectivosRESUMO
Pleural infections have high morbidity and mortality, and their incidence in all age groups is growing worldwide. Not all infectious effusions are parapneumonic and, in such cases, the organisms found in the pleural space are not the same as those observed in lung parenchyma infections. The diagnostic difficulty lies in knowing whether an infectious effusion will evolve into a complicated effusion/empyema, as the diagnostic methods used for this purpose provide poor results. The mainstays of treatment are to establish an early diagnosis and to commence an antibiotic regimen and chest drain as soon as possible. This should preferably be carried out with fine tubes, due to certain morphological, bacteriological and biochemical characteristics of the pleural fluid. Fluid analysis, particularly pH, is the most reliable method for assessing evolution. In a subgroup of patients, fibrinolytics may help to improve recovery, and their combination with DNase has been found to obtain better results. If medical treatment fails and surgery is required, video-assisted thoracoscopic surgery (VATS) is, at least, comparable to decortication by thoracotomy, so should only undertaken if previous techniques have failed. Further clinical trials are needed to analyze factors that could affect the results obtained, in order to define new evidence-based diagnostic and therapeutic strategies that provide more effective, standardized management of this disease.
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Derrame Pleural/diagnóstico , Derrame Pleural/terapia , Algoritmos , Humanos , Derrame Pleural/microbiologiaRESUMO
The determination of pleural fluid triglycerides (PF-TRIG) is useful in the diagnosis of chylothorax, but its diagnostic value for other causes of pleural effusions is unknown. The aim of this study was to evaluate the usefulness of PF-TRIG in the diagnosis of other pleural effusions and investigate the origin of their increase in these fluids. We studied 390 pleural effusions (75 tuberculous, 107 neoplastic, 39 parapneumonic, 30 miscellaneous, 42 idiopathic, and 97 transudates). The correlation was analyzed with the PF-TRIG values as the dependent variable and serum triglycerides (S-TRIG) and the pleural fluid/serum protein ratio (PF/S PROT ratio) as independent variables. The PF-TRIG was significantly higher in exudates. The sensitivity of PF-TRIG for identifying exudates was 84.3%, specificity 61.9%. The correlation between PF-TRIG and S-TRIG was significant in the exudates and in the total pleural effusions. There was a significant correlation between PF-TRIG and S-TRIG and capillary permeability, which worsened when looking at the transudates and exudates separately. No correlations were found between the PF-TRIG and the number of red cells and white cells in any of the groups. Except for diagnosing a chylothorax, the determination of triglycerides in pleural fluid does not appear to be justified. The cause of the increase in PF-TRIG in exudates could not be established because the correlations obtained were insufficient to be able to predict PF-TRIG values from their serum values and the measurement of capillary permeability.
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Quilotórax/diagnóstico , Exsudatos e Transudatos/química , Derrame Pleural/diagnóstico , Triglicerídeos/análise , Adolescente , Adulto , Idoso , Biomarcadores/análise , Permeabilidade Capilar , Quilotórax/etiologia , Quilotórax/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Derrame Pleural/metabolismo , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Tennessee , Triglicerídeos/sangue , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND: Tuberculous pleural effusions (TPE) are common. The diagnosis is often problematic. As the determination of ADA is often unavailable in some countries, the aim of this study was to evaluate the diagnostic usefulness of other data from pleural fluid analysis, in young patients from populations with high prevalence of tuberculosis (TB). METHODS: We analysed 218 patients with pleural effusion (165 tuberculous, 21 infectious, 11 neoplastic, 16 miscellaneous, 3 idiopathic). We performed two regression models; one included pleural fluid ADA values (model 1), and the other without ADA (model 2). RESULTS: Model 1 selected two variables (ADA >35U/L) and lymphocytes (>31.5%) and correctly classified 216/218 effusions (1 false negative, 1 false positive). Model 2 (without ADA) selected three variables: lymphocytes (>31.5%), fever and cough, and correctly classified 207/218 effusions (8 false negatives, 3 false positives). The sensitivity of models 1 and 2 was 99.4% and 95.2%, specificity 98.1% and 94.3% and accuracy 99% and 95%. CONCLUSIONS: In geographic areas with high prevalence of TB and a low prevalence of HIV, in young patients (Assuntos
Adenosina Desaminase/análise
, Exsudatos e Transudatos/química
, Derrame Pleural/etiologia
, Tuberculose Pleural/complicações
, Adulto
, Biomarcadores/análise
, Feminino
, Humanos
, Incidência
, Masculino
, Derrame Pleural/epidemiologia
, Derrame Pleural/metabolismo
, Prevalência
, Estudos Prospectivos
, Sensibilidade e Especificidade
, Espanha/epidemiologia
, Tuberculose Pleural/diagnóstico
, Tuberculose Pleural/epidemiologia
, Tuberculose Pleural/metabolismo
, Adulto Jovem