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BACKGROUND: Persistent respiratory symptoms and lung abnormalities post-COVID-19 are public health problems. This study evaluated biomarkers to stratify high-risk patients to the development or persistence of post-COVID-19 interstitial lung disease. METHODS: One hundred eighteen patients discharged with residual lung abnormalities compatible with interstitial lung disease (COVID-ILD patients) after a severe COVID-19 were followed for 1 year (post-COVID-ILD patients). Physical examination, pulmonary function tests, and chest high-resolution computed tomography (HRCT) were performed. Soluble forms (s) of PD-L1, PD-L2, TIM-3, and GAL-9 were evaluated in serum and cell culture supernatant, as well as T-cells subsets and the transmembrane expression of PD-L1 and PD-L2 on the cell surface. RESULTS: Eighty percent of the post-COVID-ILD patients normalized their lung function at 1-year follow-up, 8% presented COVID-independent ILD, and 12% still showed functional and HRCT alterations. PD-L2 levels were heterogeneous during acute COVID-19 (aCOVID); patients who increased (at least 30%) their sPD-L2 levels at 1 year post-COVID-19 and exhibited altered CD4/CD8 ratio showed persistence of chest tomographic and functional alterations. By contrast, patients who decreased sPD-L2 displayed a complete lung recovery. sPD-L1, sTIM-3, and sGAL-9 increased significantly during aCOVID and decreased in all patients after 1-year follow-up. CONCLUSION: Increased sPD-L2 and an altered CD4/CD8 ratio after 12 months of aCOVID are associated with the persistence of lung lesions, suggesting that they may contribute to lung damage post-COVID-19.
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Relación CD4-CD8 , COVID-19 , Pulmón , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/sangre , COVID-19/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pulmón/inmunología , Pulmón/patología , Pulmón/diagnóstico por imagen , SARS-CoV-2/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/sangre , Biomarcadores/sangre , Antígeno B7-H1/sangre , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X , Estudios de Seguimiento , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , AdultoRESUMEN
BACKGROUND: Heart failure (HF) is growing in importance as a significant cause of disease and mortality. When It is suspected, it can be ruled out if BNP values are below 100 pg/mL. Diagnostic certainty can be obtained if echocardiogram shows reduced ejection fraction, diastolic dysfunction or right-sided heart disease. Physiological changes at high altitude are known to affect BNP values. This study pretends to evaluate BNP values when used for HF diagnosis in Huancayo, Perú, a high altitude population located at 3,250 m above sea level. METHODS: This is a cross-sectional, diagnostic test type study. A total of 83 medical charts of patients with suspected HF, admitted to the Emergency Room and Internal Medicine Service of Ramiro Prialé Prialé National Hospital, were reviewed. Data processing was performed with SPSS program for Windows version 21.0. Pearson's Chi Square test was used for categorical variables analysis and ANOVA for continuos variables. P values under 0.05 were considered significant. RESULTS AND CONCLUSIONS: Medium age was 74 years. Patient's characteristics that were associated with confirmed HF and high BNP levels were the following: presence of fatigue, night cough, elevated heart rate, shortness of breath, history of lung fibrosis and decreased oxygen arterial saturation (p < 0.05) Pulmonary hypertension, mitral and tricuspid regurgitation, and cor pulmonale were also associated with higher BNP levels. Most subjects had BNP values >100 pg/mL, with low specificity for HF diagnosis (11.5 %). Individuals without heart failure had mean BNP values above 300 pg/mL; while individuals with cor pulmonale had a mean of 975 pg/mL. BNP values were high in patients with or without HF. A cut-off point of ≥130pg/mL is proposed to increase specificity. The predictive capacity of BNP for HF identification at this high altitude population is low because of a high number of false positive results.
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Altitud , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Péptido Natriurético Encefálico/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Ecocardiografía Doppler , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/diagnóstico , Hipoxia/complicaciones , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Masculino , Persona de Mediana Edad , Perú , Capacidad VitalRESUMEN
OBJECTIVE: To describe the clinical and serological patients characteristics with Microscopic Polyangiitis (MPA) and Interstitial lung disease (ILD). METHODS: Of all the patients with AAV diagnosed between 2007-2017 at the Hospital Clinico Universidad de Chile, those with MPA and ILD were selected and studied retrospectively. RESULTS: All patients were Hispanic; median age at diagnosis 65 years (32-84). 59% were female. All were positive for p-ANCA, 16 patients for MPO. Most common manifestations were constitutional symptoms, weight loss and fever. CT-Scans patterns were Usual Interstitial Pneumonia (UIP) in 10 patients, Nonspecific Interstitial Pneumonia (NSIP) in 6 and fibrosis not UIP or NSIP pattern in 1. In 6 cases, ILD was diagnosed 0.5-14 years before MPA and concomitantly in 11. CONCLUSIONS: Although infrequent, Microscopic Polyangiitis should be suspected in patients with ILD particularly if extra-pulmonary manifestations that rise the possibility of a systemic illness are present, regardless of the time elapsed between the latter and the diagnosis of this type of lung involvement. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 37-42).
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Anticuerpos Anticitoplasma de Neutrófilos/sangre , Enfermedades Pulmonares Intersticiales/sangre , Poliangitis Microscópica/sangre , Peroxidasa/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Chile , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/inmunología , Masculino , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/inmunología , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Pruebas Serológicas , Tomografía Computarizada por Rayos XRESUMEN
Interstitial lung abnormalities (ILA) represent aging-associated bilateral interstitial abnormalities in nondependent areas of the lung. However, the aging mechanisms associated with ILA remain uncertain. α-Klotho is an anti-aging molecule that decreases progressively with age, and abnormally low circulating levels of this protein have been revealed in several chronic-degenerative diseases. In this study, we evaluated α-Klotho serum concentrations in individuals with ILA, and examined whether its levels were associated with pulmonary function decline. α-Klotho was measured by ELISA in 50 respiratory asymptomatic adults with ILA and 150 healthy individuals over 60 years. Compared with controls, ILA subjects were predominantly older males, and showed lower lung diffusing capacity (DLCO), higher desaturation after exercise, and higher concentrations of serum matrix metalloprotease-7 (6.24 ± 4.1 versus 4.3 ± 1.7 ng/ml; p = 0.002). No differences were found in serum concentrations of α-Klotho. However, lower levels of this protein in ILA significantly correlated with lower values of forced vital capacity (Rho = 0.39; p = 0.005), forced expiratory volume in one second (Rho = 0.39; p = 0.005), and DLCO (Rho = 0.29, p = 0.04). These findings suggest that decreased concentrations of α-Klotho may be a predictive biomarker of accelerated decline of lung function in individuals with ILA.
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Glucuronidasa/sangre , Enfermedades Pulmonares Intersticiales/sangre , Anciano , Biomarcadores/sangre , Femenino , Humanos , Proteínas Klotho , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Metaloproteinasa 7 de la Matriz/sangre , Persona de Mediana EdadRESUMEN
The objectives of the present study were to compare the survival function of antisynthetase syndrome (ASS) Jo1-positive patients with ASS non-Jo1 patients, all with interstitial lung disease (ILD), and to evaluate other factors such as the extension of pulmonary disease and the time between the onset of symptoms and diagnosis and its association to survival in a cohort of ASS patients. Patients with ASS, all with ILD, were included. At the baseline, pulmonary function tests were realized and a high-resolution chest tomography was obtained; lung inflammation and fibrosis were measured with the Goh score and the Kazerooni index. The following autoantibodies were measured: Jo1, Ej, Oj, PL7, and PL12. Patients had to be positive for one of them in order to be included in the study. The survival function was estimated and compared with the log rank test, and the hazard ratio (HR) was estimated using Cox regression procedure. Forty-three patients were included, of which six patients died (14 %). Patients who died were different in comparison with survivors as regards the frequency of anti-Jo1 positivity: Survivors had anti-Jo1 autoantibodies more frequently (86 %) than patients who died (50 %). The univariate Cox regression analysis identified four variables associated with survival: Jo1 status, arthritis, extent of ground glass, and consolidation (inflammation) in high-resolution computed tomography (HRCT) and baseline forced vital capacity. The serological status of patients (Jo1-positive vs non-Jo1), the extent of lung inflammation in the HRCT scan, a low forced vital capacity, and arthritis are associated with survival in ASS patients.
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Autoanticuerpos/sangre , Enfermedades Pulmonares Intersticiales/sangre , Miositis/mortalidad , Capacidad Vital/fisiología , Adulto , Artritis/diagnóstico por imagen , Estudios de Cohortes , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Análisis de Regresión , Tasa de Supervivencia , Centros de Atención Terciaria , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2) are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD). METHODS: In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT) were compared with 42 RA without lung involvement (RA only). Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. RESULTS: Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P < 0.001). In the logistic regression analysis after adjustment for age, disease duration (DD), smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX) treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P = 0.003) and + RF (P = 0.002). In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P = 0.02) and with fibrosis score DD (P = 0.01), anti-CCP2 titers (P < 0.001), and MTX treatment duration (P < 0.001). CONCLUSIONS: Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.
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Anticuerpos/inmunología , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Péptidos Cíclicos/inmunología , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/sangre , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores/sangre , Estudios Transversales , Eritrocitos/inmunología , Eritrocitos/patología , Femenino , Fibrosis/tratamiento farmacológico , Fibrosis/inmunología , Fibrosis/patología , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Metotrexato/uso terapéutico , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases. OBJECTIVES: To evaluate whether serum levels of procollagen typei and iii aminoterminal propeptide (PINP and PIIINP) correlate with severity and patterns of ILD in Mexican women with SSc. METHODS: Thirty three SSc patients were assessed for disease characteristics and anti-topoisomerase antibodies (topoi), and also underwent pulmonary function tests and high-resolution computed tomography (HRCT). Nineteen patients had ILD+SSc, and 14 had no lung involvement (no ILD-SSc); data were compared with those from 45 healthy controls. PINP and PIIINP were assessed in all 3 groups. RESULTS: Patients with SSc had higher PINP and PIIINP vs controls (P=.001, P<.001, respectively). Compared to no ILD-SSc patients, those with ILD+SSc had longer disease duration in years (P=.005), higher modified Rodnan skin score (P<.001), higher Health Assessment Questionnaire-Disability-Index scores (P<.001), higher topoi U/mL (P<.001), PINP (49.28±28.63 vs. 32.12±18.58µg/L, P=.05), and PIIINP (4.33±1.03 vs. 2.67±1.26µg/L, P<.001) levels. ILD severity based on total HRCT correlated with PINP (r=.388, P=.03) and PIIINP (P=.594, P<.001). On adjusted analysis, ILD severity was associated with disease duration (P=.037), PIIINP (P=.038), and topoi (P=.045). CONCLUSIONS: PINP and PIIINP are useful markers for severe ILD+SSc, suggesting they could play a role in the follow-up of this complication in SSc.
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Colágeno Tipo I/sangre , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/etiología , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/complicaciones , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , México , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
The prevalence of interstitial lung involvement in anti-synthetase syndrome (anti-SS) may be as high as 70% and is a major contributor to morbidity and mortality. Histidyl-tRNA synthetase (Jo-1) is the most common autoantigenic target among the aminoacyl-tRNA synthetases. We report two well documented anti-SS cases where it was observed significant exposure to a known inhaled offending antigen, development of a lymphocytic interstitial lung disease (ILD) and negative auto-antibodies, interpreted at first as hypersensitivity pneumonitis. Only after 14 and 30 months, respectively, the development of systemic symptoms compatible with anti-SS and anti-Jo-1 was observed. A growing body of evidence suggests that the lungs are the environment in which Jo-1 autoimmunity may be initiated and propagated. The description of the clinical and laboratorial evolution of these patients together with accumulated evidence of biological plausibility support the hypothesis that anti-SS can follow an episode of lung inflammation secondary to inhaled antigen exposure.
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Autoinmunidad , Enfermedades Pulmonares Intersticiales/inmunología , Pulmón/inmunología , Miositis/inmunología , Anticuerpos Antinucleares/sangre , Antígenos , Proteínas Aviares/inmunología , Biomarcadores/sangre , Pulmón de Criadores de Aves/sangre , Pulmón de Criadores de Aves/tratamiento farmacológico , Pulmón de Criadores de Aves/inmunología , Quimioterapia Combinada , Exposición a Riesgos Ambientales , Femenino , Hongos/inmunología , Humanos , Inmunosupresores/uso terapéutico , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Persona de Mediana Edad , Miositis/sangre , Miositis/diagnóstico , Miositis/tratamiento farmacológico , Valor Predictivo de las Pruebas , Recurrencia , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine frequency, origin, and clinical associations of elevated serum neuron specific enolase (NSE) in systemic sclerosis (SSc). METHODS: Serum was obtained from 75 patients with SSc, 20 systemic lupus erythematosus, 8 polymyositis, 10 idiopathic interstitial lung disease, and 10 healthy volunteers. NSE status was determined in serum (in all individuals) and in platelet lysate (in volunteers and 30 patients with SSc). RESULTS: Elevated serum NSE (mean 22.6 ng/ml, range 12.1-68.2 ng/ml) was observed in 26 patients with SSc (34.6%). Those with diffuse SSc had higher serum NSE than those with limited disease (16.5 +/- 13.4 vs 9.6 +/- 5.0 ng/ml, p = 0.006). No association was found between serum NSE and lung or esophagus involvement. Patients with long-standing disease had lower serum NSE than those with early disease (10.8 +/- 7.3 vs 16.1 +/- 13.6 ng/ml, p = 0.05). Serum NSE was 19.4 +/- 13.0 ng/ml in patients with total skin score (TSS) > 20, 8.3 +/- 2.1 ng/ml in patients with TSS < 5, and 6.0 +/- 3.1 ng/ml in volunteers (p = 0.01). NSE platelet lysate concentration was 3.6 +/- 2.9 ng/ml in patients with TSS > 20, 12.4 +/- 4.1 ng/ml in those with TSS < 5, and 14.1 +/- 6.5 ng/ml in healthy individuals (p < 0.001). Volunteers and SSc patients with low TSS had comparable S/PL-NSE index (serum/platelet lysate NSE concentration) (0.42 +/- 0.16 and 0.75 +/- 0.33, respectively), both lower than SSc patients with high TSS (7.45 +/- 5.57) (p < 0.001). CONCLUSION: Elevated serum NSE was observed in one-third of SSc patients but not in other autoimmune rheumatic diseases. The inverse relationship between serum and platelet lysate NSE concentration suggests platelet activation as the origin of high serum NSE in SSc. NSE S/PL was the best discriminatory variable between healthy volunteers and SSc patients as well as between patients with high and low TSS. High serum NSE and high NSE-S/PL index seemed to be associated with SSc disease activity. Further work is warranted to investigate a possible role for this marker in assessing disease activity and therapy response.
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Plaquetas/enzimología , Fosfopiruvato Hidratasa/metabolismo , Esclerodermia Sistémica/enzimología , Adulto , Anciano , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/enzimología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/enzimología , Masculino , Persona de Mediana Edad , Activación Plaquetaria/fisiología , Polimiositis/sangre , Polimiositis/enzimología , Esclerodermia Sistémica/sangreRESUMEN
Serum levels of KL-6 were examined in 8 cases of juvenile dermatomyositis: 3 with interstitial lung disease (ILD) and 5 without ILD. The KL-6 levels were elevated in the ILD cases and correlated with the degree of computed tomography findings. The measurement of serum KL-6 levels is useful for evaluating juvenile dermatomyositis-associated ILD.