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1.
Eur Respir J ; 58(6)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34140301

RESUMO

BACKGROUND: The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin or other manifestations. While glucocorticoids remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. Glucocorticoid-sparing alternatives are available. The presented treatment guidelines aim to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations. METHODS: A European Respiratory Society Task Force committee composed of clinicians, methodologists and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations. RESULTS: The Task Force committee delivered 12 recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac and neurologic disease as well as fatigue. One PICO question regarding small-fibre neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation. CONCLUSIONS: There are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment.


Assuntos
Qualidade de Vida , Sarcoidose , Fadiga , Humanos , Sarcoidose/diagnóstico , Sarcoidose/terapia
2.
Lung ; 199(3): 281-288, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33942129

RESUMO

BACKGROUND: Galectins are proteins that bind ß-galactosides such as N-acetyllactosamine present in N-linked and O-linked glycoproteins and that seem to be implicated in inflammatory and immune responses as well as fibrotic mechanisms. This preliminary study investigated serum galectins as clinical biomarkers in lung transplant patients with chronic lung allograft dysfunction (CLAD), phenotype bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: Nineteen lung transplant patients [median age (IQR), 55 (45-62) years; 53% males] were enrolled in the study. Peripheral blood concentrations of galectins-1, 3 and 9 were determined with commercial ELISA kits. RESULTS: Galectin-1 concentrations were higher in BOS than in stable LTX patients (p = 0.0394). In logistic regression analysis, testing BOS group as dependent variable with Gal-1 and 3 as independent variables, area under the receiver operating characteristics (AUROC) curve was 98.9% (NPV 90% and PPV 88.9%, p = 0.0003). With the stable LTX group as dependent variable and Gal-1, 3 and 9 as independent variables, AUROC was 92.6% (NPV 100% and PPV 90%, p = 0.0023). In stable patients were observed an inverse correlation of Gal-3 with DLCO% and KCO%, and between Gal-9 and KCO%. CONCLUSION: Galectins-1, 3 and 9 are possible clinical biomarkers in lung transplant patients with diagnostic and prognostic meaning. These molecules may be directly implicated in the pathological mechanisms of BOS. The hypothesis that they could be new therapeutic targets in BOS patients is intriguing and also worth exploring.


Assuntos
Galectinas/sangue , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/sangue , Insuficiência Respiratória/cirurgia , Adulto , Aloenxertos , Biomarcadores/sangue , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/etiologia , Prognóstico
3.
Respir Res ; 21(1): 6, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906975

RESUMO

BACKGROUND: Serum chitotriosidase is a promising biomarker that has shown high specificity and sensitivity in patients with sarcoidosis. The aim of this study was to investigate correlations between serum chitotriosidase, clinical phenotypes, disease localizations and different radiological lung involvement and to identify clinical features associated with over-expression of chitotriosidase in a large cohort of sarcoidosis patients. METHODS: Chitotriosidase activity was evaluated in a population of 694 consecutive patients (males 39%, age 55.8 ± 12.8 years). Clinical and respiratory functional characteristics, Clinical Outcome Scale (COS) classification, clinical phenotypes proposed by the GenPhenResA project, and radiological assessment, including CT scan, were collected. Serum sampling and clinical and functional assessments at follow-up were also included. RESULTS: Significantly higher chitotriosidase activity was observed in sarcoidosis patients than in healthy controls (p < 0.0001). Evidence of lung fibrosis with reticular abnormalities and traction bronchiectasis at High resolution CT, presence of multiple extrapulmonary sarcoid localizations and increased 24-h urinary excretion of calcium were associated with significantly higher chitotriosidase activity (p < 0.005). Patients with remitted or minimal disease had lower values of chitotriosidase than patients with persistent disease. At follow-up, patients who required an increase in steroid dose showed an increase in its activity. CONCLUSIONS: Chitotriosidase is a reliable biomarker of sarcoidosis. It is increased in patients with sarcoidosis correlating with disease activity, severity and multiorgan dissemination. Steroid therapy tended to reduce chitotriosidase expression, however it responded in cases of disease relapse.


Assuntos
Hexosaminidases/sangue , Sarcoidose/enzimologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Sarcoidose/diagnóstico , Índice de Gravidade de Doença
5.
Am J Respir Crit Care Med ; 199(5): 622-630, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30141961

RESUMO

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a variable and unpredictable course. OBJECTIVES: To determine whether BAL cell gene expression is predictive of survival in IPF. METHODS: This retrospective study analyzed the BAL transcriptome of three independent IPF cohorts: Freiburg (Germany), Siena (Italy), and Leuven (Belgium) including 212 patients. BAL cells from 20 healthy volunteers, 26 patients with sarcoidosis stage III and IV, and 29 patients with chronic obstructive pulmonary disease were used as control subjects. Survival analysis was performed by Cox models and component-wise boosting. Presence of airway basal cells was tested by immunohistochemistry and flow cytometry. MEASUREMENTS AND MAIN RESULTS: A total of 1,582 genes were predictive of mortality in the IPF derivation cohort in univariate analyses adjusted for age and sex at false discovery rate less than 0.05. A nine-gene signature, derived from the discovery cohort (Freiburg), performed well in both replication cohorts, Siena (P < 0.0032) and Leuven (P = 0.0033). nCounter expression analysis confirmed the array results (P < 0.0001). The genes associated with mortality in BAL cells were significantly enriched for genes expressed in airway basal cells. Further analyses by gene expression, flow cytometry, and immunohistochemistry showed an increase in airway basal cells in BAL and tissues of IPF compared with control subjects, but not in chronic obstructive pulmonary disease or sarcoidosis. CONCLUSIONS: Our results identify and validate a BAL signature that predicts mortality in IPF and improves the accuracy of outcome prediction based on clinical parameters. The BAL signature associated with mortality unmasks a potential role for airway basal cells in IPF.


Assuntos
Líquido da Lavagem Broncoalveolar/citologia , Fibrose Pulmonar Idiopática/metabolismo , Mucosa Respiratória/metabolismo , Idoso , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Fibrose Pulmonar Idiopática/mortalidade , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
6.
Monaldi Arch Chest Dis ; 90(2)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32362107

RESUMO

Acute exacerbations (AEs) are among the main causes of death in idiopathic pulmonary fibrosis (IPF) patients. In this study proteomic comparative analysis of bronchoalveolar lavage (BAL) fluid samples was performed in stable IPF patients versus AEs IPF group to identify AE pathogenetic mechanisms and novel potential predictive biomarkers. A functional proteomic analysis of BAL fluid samples from stable and AE-IPF patients was conducted in a population of 27 IPF patients. Fifty-one differentially abundant spots were observed and identified by mass spectrometry. Enrichment analysis found proteins of interest involved in the regulation of macrophages and lipid metabolism receptors. In acute exacerbation IPF group, differentially abundant proteins were involved in propagation of the ß-catenin WNT transduction signal, and proteins up-regulated in lung carcinogenesis (IGKC, S100A9, PEDF, IGHG1, ALDOA, A1AT, HPT, CO3 and PIGR) and acute phase proteins involved in protease-antiprotease imbalance (such as A1AT fragments). Dot-blot analysis of A1AT C-36 peptide allowed validating our findings, confirming up-regulation in AE IPF patients and suggesting its potential pathogenetic role. A crucial role of protease/antiprotease imbalance, clathrin-mediated endocytosis signalling and carcinogenesis emerged in IPF patients developing acute exacerbations.


Assuntos
Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , Fibrose Pulmonar Idiopática/metabolismo , Proteômica/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/metabolismo , Progressão da Doença , Endocitose/fisiologia , Feminino , Humanos , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Pulmão/fisiopatologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Transdução de Sinais/genética , Regulação para Cima , beta Catenina/metabolismo
7.
Rheumatology (Oxford) ; 58(1): 165-178, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30239835

RESUMO

Objective: SSc is a rare severe connective tissue disorder. Its prognosis is mainly related to the development of pulmonary fibrosis (PF)-SSc and pulmonary arterial hypertension. No known therapy for PF-SSc modifies progressive lung fibrotic involvement. Research is therefore aimed at a deeper understanding of complex pathogenetic mechanisms and the possibility of new prognostic biomarkers and therapeutic targets. Methods: Towards the first of these aims, we conducted functional proteomic analysis of bronchoalveolar lavage samples from PF-SSc patients and smoker and non-smoker controls. Results: The differential expression pattern revealed by principal component analysis highlighted a specific protein profile of PF-SSc with respect to control samples, and enrichment analysis shed light on process networks involved in pathogenesis. The proteins identified are known to be involved in lung inflammation of PF-SSc-induced IL6 signalling, the complement system, innate immunity, Jak-STAT, the kallikrein-kinin system, blood coagulation, the immune response mediated by phagocytosis and phagosomes in antigen presentation. In particular, our MetaCore network suggested C3a, APOAI, 14-3-3ε, SPFA2 and S100A6 as potential biomarkers; these are upstream molecules involved in lung fibrosis, innate immunity and vascular damage occurring in PF-SSc. Conclusion: This report provides a molecular overview of pathological processes in PF-SSc, pinpointing possible new disease biomarkers and therapeutic targets.


Assuntos
Proteínas 14-3-3/análise , Lavagem Broncoalveolar/métodos , Proteínas de Ciclo Celular/análise , Proteômica/métodos , Fibrose Pulmonar/genética , Proteína A6 Ligante de Cálcio S100/análise , Escleroderma Sistêmico/genética , Idoso , Biomarcadores/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/imunologia , Escleroderma Sistêmico/complicações
8.
Lung ; 197(1): 95-99, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30456701

RESUMO

BACKGROUND: Helicobacter pylori (HP) is a spiral, gram-negative, microaerophilic bacterium that colonises the human gastric mucosa and is associated with gastrointestinal and extragastrointestinal disorders. Since no data are yet available on HP infection in lung transplant patients, we evaluated the prevalence and impact of HP infection in a population of such patients. METHODS: Sixty-seven lung transplant patients were enrolled in the study (35 females and 32 males, age 48.4 ± 13.3 years), 54 underwent bilateral and 13 single lung transplant. Serum antibodies against HP and CagA were assayed in all subjects. RESULTS: The prevalence of HP infection in lung transplant patients was similar to that in the general population (49.25% vs. 51.4%), whereas HP-positive patients showed lower CagA positivity (9% vs. 50.2%, p < 0.0001). There was a higher prevalence of HP infection in patients who underwent lung transplant because of pulmonary fibrosis (p = 0.049), and a lower prevalence in COPD patients (p = 0.011). No correlation was found between HP infection in lung transplant patients and graft outcome. No differences in primary graft dysfunction, acute rejection or bronchiolitis obliterans syndrome-free survival were found. However, more patients who required three or more post-transplant re-hospitalisations were observed among HP-positive patients. CONCLUSIONS: The prevalence of HP infection in lung transplant patients was comparable to that of the general population and to that reported in heart and kidney transplant recipients. It did not seem to impact short-, mid- or long-term lung allograft outcome. H. pylori infection did not prove to be clinically relevant in lung transplant patients.


Assuntos
Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Pneumopatias/cirurgia , Transplante de Pulmão , Adulto , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Itália/epidemiologia , Pneumopatias/diagnóstico , Pneumopatias/epidemiologia , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Prevalência , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
Lung ; 197(2): 147-153, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30758708

RESUMO

INTRODUCTION: Familial pulmonary fibrosis (FPF) is defined as an idiopathic diffuse parenchymal lung disease affecting two or more members of the same primary biological family. The aim of this study was to compare disease progression and tolerance to pirfenidone in a population of FPF patients who presented with radiological and/or histological evidence of UIP, and a group of idiopathic pulmonary fibrosis (IPF) patients. METHODS: Seventy-three patients (19 with FPF and 54 with IPF) were enrolled and data were collected retrospectively at 6, 12 and 24 months follow-up. RESULTS: FPF patients were statistically younger and more frequently females. A significantly greater decline in FVC and DLCO was recorded in FPF than in IPF patients at 24 months follow-up. At the 6-min walking test, walked distance declined significantly in FPF patients than IPF at 24 months. No statistically significant differences in drug tolerance or side effects were recorded between groups. CONCLUSION: Different rate of progression was observed in patients with IPF and FPF on therapy with pirfenidone; our findings may not be due to lack of effectiveness of therapy, but to the different natural history and evolution of these two conditions. Pirfenidone was well tolerated by FPF and IPF patients. Specific unbiased randomized clinical trials on larger populations to validate our preliminary exploratory results are needed.


Assuntos
Fibrose Pulmonar Idiopática/tratamento farmacológico , Pulmão/efeitos dos fármacos , Piridonas/uso terapêutico , Idoso , Progressão da Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
10.
Eur Respir J ; 51(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29371378

RESUMO

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.


Assuntos
Fenótipo , Sarcoidose/diagnóstico , Sarcoidose/fisiopatologia , Abdome , Doença Aguda , Adulto , Idoso , Europa (Continente) , Olho/fisiopatologia , Oftalmopatias/fisiopatologia , Feminino , Volume Expiratório Forçado , Genótipo , Humanos , Artropatias/fisiopatologia , Pulmão/fisiopatologia , Pneumopatias/fisiopatologia , Linfonodos/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pele/fisiopatologia , Dermatopatias/fisiopatologia , Atenção Terciária à Saúde , População Branca
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